NERVOUS SYSTEM

What is the nervous system?

Your nervous system is the control and communication system of the body. Its job is to send
and receive messages. Your nervous system controls all your thoughts and movements.
Parts of the nervous system
Neurons
The cells that make up the nervous system are called neurons. Long, stringy neurons are
perfect for carrying the electrical messages that are the "language" of the nervous system.
Brain
The brain is the command center of your entire body. The brain is the body's main
information center. It is made of billions of neurons. The brain helps the body respond to the
information it receives from the senses. The brain also processes thoughts. When you think,
neurons in your brain are working.
The brain has three main parts. The largest is the cerebrum, which controls vision, touch, and
other senses. It also handles movements you have control over. Thinking takes place in the
cerebrum. The cerebellum is another section of the brain. The cerebellum helps control balance
and coordination. Another part of the brain is called the brain stem. The brain stem is the link to
the spinal cord and it also controls digestion, breathing, and heartbeat.
Spinal Cord
The spinal cord is a tube of neurons that runs up the spine and attaches to the brain stem.
Information from nerves that branch out to the rest of the body goes to the spinal cord. Some
messages are processed by the spinal cord but most information is sent on to the brain.

Adrenoleukodystrophy
Adrenoleukodystrophy (ALD) refers to several different inherited conditions that affect the
nervous system and adrenal glands. Other names for it are adrenomyeloneuropathy, childhood
cerebral ALD, and Schilder-Addison Complex.
The gene that causes ALD was identified in 1993. It occurs in about 1 in 20,000 people and
mainly affects men. Women can carry ALD without having any symptoms. The symptoms,
treatments, and prognosis of ALD vary depending on which type is present. ALD is not curable,
but the progression can be slowed in some cases.
Types of Adrenoleukodystrophy
Childhood cerebral ALD mainly affects children who are between 4 and 10 years old. It can
progress rapidly if the condition is not found early enough.
Adrenomyelopathy primarily affects male adults. It is milder than childhood cerebral ALD. It
also progresses slowly in comparison.
Addisons disease is the third type of ALD. It is also known adrenal insufficiency. Addisons
disease occurs when your adrenal glands dont make enough hormones.
Part 3 of 8: Causes
Causes and Risk Factors
The adrenoleukodystrophy protein (ALDP) helps your body break down very long chain fatty
acids (VLCFA). When this doesnt happen, the fatty acids build up inside your body instead.
This can harm the outer layer of the cells in your spinal cord, brain, adrenal glands, and testes.
People with ALD have mutations in the gene that makes ALDP. Their bodies do not make
enough ALDP.
Men are typically affected by ALD at an earlier age than women and usually have more severe
symptoms. ALD affects males more than females because it is X-linked. This means that the
gene mutation that causes it is on the X chromosome. Men only have one X chromosome, while
women have two copies of it. That means that they can have one normal and one mutant copy of
the gene.
Women with only one copy of the mutation have much milder symptoms than men. In some
cases they dont have symptoms at all. Their normal copy of the gene makes enough ALDP to

help mask their symptoms. Most women with ALD have adrenomyelopathy. Addisons disease
and childhood cerebral ALD are less common.
Symptoms of Adrenoleukodystrophy

muscle spasms
seizures
trouble swallowing
loss of hearing
trouble with language comprehension
impaired vision
hyperactivity
paralysis
coma
deterioration of fine motor control
crossed eyes
Signs of adrenomyelopathy include:

poor control of urination

weak muscles
stiffness in the legs
difficulty thinking and remembering visual perceptions
Signs of adrenal gland failure or Addisons disease include:

poor appetite
weight loss
decreased muscle mass
vomiting
weak muscles
coma
darker areas of skin color or pigmentation
Treatment of Adrenoleukodystrophy
Treatment methods depend on the type of ALD. Steroids can be used to treat Addisons disease.
There are no specific methods for treating the other types of ALD.

switching to a diet that contains low levels of VLCFAs

taking Lorenzos oil to help lower elevated VLCFA levels
medications to relieve symptoms such as seizures
physical therapy to loosen muscles and reduce spasms
Doctors continue to look for new ALD treatments. Some are experimenting with the use of bone
marrow transplants. These may be able to help children with childhood cerebral ALD when it is
diagnosed early.

Alzheimer's disease
Alzheimer's disease is the most common cause of dementia. The word dementia describes a set
of symptoms that can include memory loss and difficulties with thinking, problem-solving or
language. These symptoms occur when the brain is damaged by certain diseases, including
Alzheimer's disease. This factsheet describes the symptoms of Alzheimer's disease, how it is
diagnosed, and the factors that can put someone at risk of developing it. It also describes the
treatments and support that are currently available.
Alzheimer's disease, named after the doctor who first described it (Alois Alzheimer), is a
physical disease that affects the brain. There are more than 520,000 people in the UK with
Alzheimer's disease. During the course of the disease, proteins build up in the brain to form
structures called 'plaques' and 'tangles'. This leads to the loss of connections between nerve cells,
and eventually to the death of nerve cells and loss of brain tissue. People with Alzheimer's also
have a shortage of some important chemicals in their brain. These chemical messengers help to
transmit signals around the brain. When there is a shortage of them, the signals are not
transmitted as effectively. As discussed below, current treatments for Alzheimer's disease can
help boost the levels of chemical messengers in the brain, which can help with some of the
symptoms.
Alzheimer's is a progressive disease. This means that gradually, over time, more parts of the
brain are damaged. As this happens, more symptoms develop. They also become more severe.

Symptoms
The symptoms of Alzheimer's disease are generally mild to start with, but they get worse over
time and start to interfere with daily life.

There are some common symptoms of Alzheimer's disease, but it is important to remember that
everyone is unique. Two people with Alzheimer's are unlikely to experience the condition in
exactly the same way.
For most people with Alzheimer's, the earliest symptoms are memory lapses. In particular, they
may have difficulty recalling recent events and learning new information. These symptoms occur
because the early damage in Alzheimer's is usually to a part of the brain called the hippocampus,
which has a central role in day-to-day memory. Memory for life events that happened a long time
ago is often unaffected in the early stages of the disease.
Memory loss due to Alzheimer's disease increasingly interferes with daily life as the condition
progresses. The person may:

lose items (eg keys, glasses) around the house

struggle to find the right word in a conversation or forget someone's name
forget about recent conversations or events
get lost in a familiar place or on a familiar journey
forget appointments or anniversaries.

Although memory difficulties are usually the earliest symptoms of Alzheimer's, someone with
the disease will also have or go on to develop problems with other aspects of thinking,
reasoning, perception or communication. They might have difficulties with:

language struggling to follow a conversation or repeating themselves

visuospatial skills problems judging distance or seeing objects in three dimensions;
navigating stairs or parking the car become much harder
concentrating, planning or organising difficulties making decisions, solving
problems or carrying out a sequence of tasks (eg cooking a meal)
orientation becoming confused or losing track of the day or date.

A person in the earlier stages of Alzheimer's will often have changes in their mood. They may
become anxious, irritable or depressed. Many people become withdrawn and lose interest in
activities and hobbies.
Later stages
As Alzheimer's progresses, problems with memory loss, communication, reasoning and
orientation become more severe. The person will need more day-to-day support from those who
care for them.

Some people start to believe things that are untrue (delusions) or less often see or hear things
which are not really there (hallucinations).
Many people with Alzheimer's also develop behaviours that seem unusual or out of character.
These include agitation (eg restlessness or pacing), calling out, repeating the same question,
disturbed sleep patterns or reacting aggressively. Such behaviours can be distressing or
challenging for the person and their carer. They may require separate treatment and management
to memory problems.
In the later stages of Alzheimer's disease someone may become much less aware of what is
happening around them. They may have difficulties eating or walking without help, and become
increasingly frail. Eventually, the person will need help with all their daily activities.
How quickly Alzheimer's disease progresses, and the life expectancy of someone with it, vary
greatly. On average, people with Alzheimer's disease live for eight to ten years after the first
symptoms. However, this varies a lot, depending particularly on how old the person was when
they first developed Alzheimer's. For more information see factsheet 458, The progression of
Alzheimer's disease and other dementias and factsheet 417, The later stages of dementia.
Mixed dementia
An estimated 10 per cent of people with dementia have more than one type at the same time.
This is called mixed dementia. The most common combination is Alzheimer's disease
with vascular dementia (caused by problems with the blood supply to the brain). The symptoms
of this kind of mixed dementia are a mixture of the symptoms of Alzheimer's disease
and vascular dementia.
Atypical Alzheimer's disease
In some people with Alzheimer's disease the earliest symptoms are not memory loss. This is
called atypical Alzheimer's disease. The underlying damage (plaques and tangles) is the same,
but the first part of the brain to be affected is not the hippocampus.
Atypical Alzheimer's disease is uncommon in those diagnosed when they are over 65. It accounts
for around five per cent of all Alzheimer's in this age group. It is, however, more common in
people diagnosed when they are under 65 (early-onset Alzheimer's disease). In this age group it
represents up to one-third of cases.
The atypical forms of Alzheimer's disease are as follows:

Posterior cortical atrophy (PCA) occurs when there is damage to areas at the back
and upper-rear of the brain. These are areas that process visual information and deal with

spatial awareness. This means the early symptoms of PCA are often problems identifying
objects or reading, even if the eyes are healthy. Someone may also struggle to judge
distances when going down stairs, or seem uncoordinated (for example when dressing).

Logopenic aphasia involves damage to the areas in the left side of the brain that
produce language. The person's speech becomes laboured with long pauses.

Frontal variant Alzheimer's disease involves damage to the lobes at the front of the
brain. The symptoms are problems with planning and decision-making. The person may also
behave in socially inappropriate ways or seem not to care about the feelings of others.
Who gets Alzheimer's disease?
Most people who develop Alzheimer's disease do so after the age of 65, but people under this age
can also develop it. This is called early-onset Alzheimer's disease, a type ofyoung-onset
dementia. In the UK there are over 40,000 people under the age of 65 with dementia.
Developing Alzheimer's disease is linked to a combination of factors, explained in more detail
below. Some of these risk factors (eg lifestyle) can be controlled, but others (eg age and genes)
cannot. For more information see factsheet 450, Am I at risk of developing dementia?
Age
Age is the greatest risk factor for Alzheimer's. The disease mainly affects people over 65. Above
this age, a person's risk of developing Alzheimer's disease doubles approximately every five
years. One in six people over 80 have dementia.
Gender
For reasons that are not clear, there are about twice as many women as men over 65 with
Alzheimer's disease. This difference is not fully explained by the fact that women on average live
longer than men. It may be that Alzheimer's in women is linked to a lack of the hormone
oestrogen after the menopause.
Genetic inheritance
Many people fear that the disease may be passed down to them from a parent or grandparent.
Scientists are investigating the genetic background to Alzheimer's. There are a few families with
a very clear inheritance of Alzheimer's from one generation to the next. In such families the
dementia tends to develop well before age 65. However, Alzheimer's disease that is so strongly
inherited is extremely rare.
In the vast majority of people, the influence of genetics on risk of Alzheimer's disease is much
more subtle. A number of genes are known to increase or reduce a person's chances of

developing Alzheimer's. For someone with a close relative (parent or sibling) who was diagnosed
with Alzheimer's when over 65, their own risk of developing the disease is increased. However,
this does not mean that Alzheimer's is inevitable, and everyone can reduce their risk by living a
healthy lifestyle.
For more information see factsheet 405, Genetics of dementia.
People with Down's syndrome are at particular risk of developing Alzheimer's disease, because
of a difference in their genetic makeup. For more information see factsheet 430, Learning
disabilities and dementia.
Health and lifestyle
Medical conditions such as diabetes, stroke and heart problems, as well as high blood pressure,
high cholesterol and obesity in mid-life, are all known to increase the risk of both Alzheimer's
disease and vascular dementia. Anyone can reduce their risk by keeping these under control.
Depression is a probable risk factor for dementia; getting it treated early is important.
People who adopt a healthy lifestyle, especially from mid-life onwards, are less likely to develop
Alzheimer's disease. This means taking regular physical exercise and keeping to a healthy
weight, not smoking, eating a healthy balanced diet and drinking only in moderation.
Leading an active lifestyle that combines regular physical, social and mental activity will help to
lower risk.

Amyotrophic lateral sclerosis

What is amyotrophic lateral sclerosis?
Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease, is a rapidly
progressive, invariably fatal neurological disease that attacks the nerve cells (neurons)
responsible for controlling voluntary muscles. The disease belongs to a group of disorders known
as motor neuron diseases, which are characterized by the gradual degeneration and death of
motor neurons.
Motor neurons are nerve cells located in the brain, brainstem, and spinal cord that serve as
controlling units and vital communication links between the nervous system and the voluntary
muscles of the body. Messages from motor neurons in the brain (called upper motor neurons) are
transmitted to motor neurons in the spinal cord (called lower motor neurons) and from them to

particular muscles. In ALS, both the upper motor neurons and the lower motor neurons
degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles
gradually weaken, waste away (atrophy), and twitch (fasciculations) . Eventually, the ability of
the brain to start and control voluntary movement is lost.
ALS causes weakness with a wide range of disabilities (see section titled "What are the
symptoms?"). Eventually, all muscles under voluntary control are affected, and patients lose their
strength and the ability to move their arms, legs, and body. When muscles in the diaphragm and
chest wall fail, patients lose the ability to breathe without ventilatory support. Most people with
ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms.
However, about 10 percent of ALS patients survive for 10 or more years.
Although the disease usually does not impair a person's mind or intelligence, several recent
studies suggest that some ALS patients may have alterations in cognitive functions such
as depression and problems with decision-making and memory.
ALS does not affect a person's ability to see, smell, taste, hear, or recognize touch. Patients
usually maintain control of eye muscles and bladder and bowel functions, although in the late
stages of the disease most patients will need help getting to and from the bathroom.
What are the symptoms of ALS?
The onset of ALS may be so subtle that the symptoms are frequently overlooked. The earliest
symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting
an arm or a leg; slurred and nasal speech; or difficulty chewing or swallowing. These general
complaints then develop into more obvious weakness or atrophy that may cause a physician to
suspect ALS.
The parts of the body affected by early symptoms of ALS depend on which muscles in the body
are damaged first. In some cases, symptoms initially affect one of the legs, and patients
experience awkwardness when walkingor running or they notice that they are tripping or
stumbling more often. Some patients first see the effects of the disease on a hand or arm as they
experience difficulty with simple tasks requiring manual dexterity such as buttoning a shirt,
writing, or turning a key in a lock. Other patients notice speech problems.
Regardless of the part of the body first affected by the disease, muscle weakness and atrophy
spread to other parts of the body as the disease progresses. Patients have increasing problems
with moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms
of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated
reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called
Babinski's sign (the large toe extends upward as the sole of the foot is stimulated in a certain

way) also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration
include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can
be seen under the skin (fasciculations).
To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower
motor neuron damage that cannot be attributed to other causes.
Although the sequence of emerging symptoms and the rate of disease progression vary from
person to person, eventually patients will not be able to stand or walk, get in or out of bed on
their own, or use their hands and arms. Difficulty swallowing and chewing impair the patient's
ability to eat normally and increase the risk of choking. Maintaining weight will then become a
problem. Because the disease usually does not affect cognitive abilities, patients are aware of
their progressive loss of function and may become anxious and depressed. A small percentage of
patients may experience problems with memory or decision-making, and there is growing
evidence that some may even develop a form of dementia. Health care professionals need to
explain the course of the disease and describe available treatment options so that patients can
make informed decisions in advance. In later stages of the disease, patients have difficulty
breathing as the muscles of the respiratory system weaken. Patients eventually lose the ability to
breathe on their own and must depend on ventilatory support for survival. Patients also face an
increased risk of pneumonia during later stages of ALS.
What causes ALS?
The cause of ALS is not known, and scientists do not yet know why ALS strikes some people
and not others. An important step toward answering that question came in 1993 when scientists
supported by the National Institute of Neurological Disorders and Stroke (NINDS) discovered
that mutations in the gene that produces the SOD1 enzyme were associated with some cases of
familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused
by free radicals. Free radicals are highly reactive molecules produced by cells during normal
metabolism. If not neutralized, free radicals can accumulate and cause random damage to the
DNA and proteins within cells. Although it is not yet clear how the SOD1 gene mutation leads to
motor neuron degeneration, researchers have theorized that an accumulation of free radicals may
result from the faulty functioning of this gene. In support of this, animal studies have shown that
motor neuron degeneration and deficits in motor function accompany the presence of the SOD1
mutation.
Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is
one of the chemical messengers or neurotransmitters in the brain. Scientists have found that,
compared to healthy people, ALS patients have higher levels of glutamate in the serum and
spinal fluid. Laboratory studies have demonstrated that neurons begin to die off when they are
exposed over long periods to excessive amounts of glutamate. Now, scientists are trying to

understand what mechanisms lead to a buildup of unneeded glutamate in the spinal fluid and
how this imbalance could contribute to the development of ALS.
Autoimmune responses -- which occur when the body's immune system attacks normal cells -have been suggested as one possible cause for motor neuron degeneration in ALS. Some
scientists theorize that antibodies may directly or indirectly impair the function of motor neurons,
interfering with the transmission of signals between the brain and muscles.
In searching for the cause of ALS, researchers have also studied environmental factors such as
exposure to toxic or infectious agents. Other research has examined the possible role of dietary
deficiency or trauma. However, as of yet, there is insufficient evidence to implicate these factors
as causes of ALS.
Future research may show that many factors, including a genetic predisposition, are involved in
the development of ALS.

Angelman syndrome
Introduction
Angelman syndrome is a genetic disorder that affects the nervous system and causes severe
physical and intellectual disability.
It's relatively rare, occurring in around 1 in 16,000 people.
Typical characteristics of Angelman syndrome include:

delayed development (usually noticeable from 6-12 months of age)

severe language impairment with little or no speech

movement and balance problems (ataxia)

frequent seizures (epilepsy) in around 85% of cases
a small head size (microcephaly)

sociable behaviour with frequent smiling

In most cases, Angelman syndrome isn't inherited from your parents, and the genetic anomaly
responsible for the syndrome occurs by chance around the time of conception. However, in some
families, more than one child is affected (see below).

Characteristics of Angelman syndrome

The typical characteristics of Angelman syndrome aren't usually apparent at birth.
A child with the syndrome will begin to show signs of delayed development around 6-12 months,
such as being unable to sit unsupported or make babbling noises. Later, they may not speak at all
or may only be able to say a few words.
The movement of a child with Angelman syndrome will also be affected. They may have
difficulty walking due to problems with balance and co-ordination (ataxia), their arms may
tremble or move jerkily, and their legs may be stiffer than normal.
A number of distinctive behaviours are also associated with Angelman syndrome. These may
include:

frequent laughter and smiling, with little stimulus

being easily excitable, often flapping the hands

being restless (hyperactive)

having a short attention span

problems sleeping and needing less sleep than other children

By around two years of age, an abnormally small head which is flat at the back
(microbrachycephaly) will often be noticeable in children with Angelman syndrome. They may
also start to have seizures (fits) around this age.
Other possible features of the syndrome include:

sticking the tongue out

crossed eyes (strabismus)

pale skin, and light-coloured hair and eyes

a wide mouth with widely spaced teeth

a side-to-side curvature of the spine (scoliosis)

walking with arms in the air

a fascination with water

Some young babies with Angelman syndrome may have problems feeding because they're
unable to co-ordinate sucking and swallowing. In such cases, a high-calorie formula may be
recommended to help the baby gain weight, or they may need to be treated for reflux.

What causes Angelman syndrome?

The typical characteristics of Angelman syndrome are caused when a gene, known as UBE3A, is
either absent or malfunctions. A gene is a single unit of DNA.
A child usually inherits one copy of the UBE3A gene from each parent. Both copies are
switched on (active) in most of the body's tissues. However, in certain areas of the brain, only the
gene inherited from the mother is active.
In most cases of Angelman syndrome (about 70%), the child's maternal copy of the UBE3A gene
is missing, which means there's no active copy of the UBE3A gene in the child's brain.
In around 11% of cases, the maternal copy of the UBE3A gene is altered (mutated).
In a small number of cases, Angelman syndrome occurs when a child inherits two copies of
chromosome 15 from the father, rather than inheriting one from each parent. It can also
occur when the copy of the UBE3A gene that comes from the mother, behaves like it came from
the father. This is known as an "imprinting defect".
In about 10-15% of cases, the cause of Angelman syndrome is unknown. It's thought that
most children in these unexplained cases may have different conditions involving other genes or
chromosomes.
Diagnosing Angelman syndrome
Angelman syndrome may be suspected if a child's development is delayed and they have the
syndrome's distinctive characteristics (see above).
A blood sample can be taken to confirm the diagnosis. A number of genetic tests will be carried
out on the sample. These may include:

chromosome analysis - to see if any parts of the chromosomes are missing

fluorescence in situ hybridisation (FISH) - used to check chromosome 15 deletions
DNA methylation - shows whether the genetic material on both the mothers and fathers
chromosomes is active; it can detect deletions, uniparental disomy and imprinting defects
UBE3A gene mutation analysis - if the results of DNA methylation are normal, UBE3A
gene sequencing can be used to see whether the maternal copy of the gene is altered

For each child with Angelman syndrome, it's important to know the genetic change that caused
the condition to determine the risk of it occurring again in another child.

Most children with Angelman syndrome are diagnosed between the ages of 18 months and
6 years, when the typical physical and behavioural symptoms become apparent.
If your child is diagnosed with Angelman syndrome, you should be given the opportunity to
discuss the genetic diagnosis and implications with a genetic doctor.

Charcot-Marie-Tooth disease (CMT)

Charcot-Marie-Tooth disease (CMT) is a neurological disorder named after the three physicians
who first described it in 1886 Jean-Martin Charcot and Pierre Marie of France, and Howard
Henry Tooth of the United Kingdom.
CMT causes damage to the peripheral nerves, which carry signals from the brain and spinal cord
to the muscles, and relay sensations, such as pain and touch, to the brain and spinal cord from the
rest of the body. There are a number of types of CMT.
What are the symptoms of CMT?
CMT causes muscle weakness and atrophy, and some loss of sensation in the feet, the lower legs,
the hands and the forearms. It also often causes contractures (stiffened joints due to abnormal
tightening of muscles and associated tissues), and sometimes, curvature of the spine (scoliosis).
At the severe end of the CMT spectrum, the disease can affect nerves other than those that go to
and from the extremities. If the nerves that go to and from the diaphragm or intercostal (between
the ribs) muscles are affected, respiratory impairment can result. For more, see Signs and
Symptoms.
What causes CMT?
CMT is caused by defects in the genes for proteins that affect axons fibers that carry electrical
signals between the brain and spinal cord and the rest of the body or in the genes for proteins
that affect myelin, a coating on axons that insulates and nourishes them.
More than 30 genes have been implicated in CMT, each one linked to a specific type (and in
many cases, more than one type) of the disease.
CMT can be inherited in several ways: autosomal dominant (through a faulty gene contributed
by either parent); autosomal recessive (through a faulty gene contributed by each parent); or X-

linked (through a gene on the X chromosome contributed by either parent.) For more on causes
and inheritance patterns in CMT, see Causes/Inheritance.

Hearing Loss
(Deafness)
What are forms of hearing loss?
Hearing loss, or deafness, can be present at birth (congenital), or become evident later in life
(acquired). The distinction between acquired and congenital deafness specifies only the time that
the deafness appears. It does not specify whether the cause of the deafness is genetic (inherited).
Acquired deafness may or may not be genetic. For example, it may be a manifestation of a
delayed-onset form of genetic deafness. Alternatively, acquired deafness may be due to damage
to the ear due to noise or from other conditions.
Congenital deafness similarly may or may not be genetic. For example, it may be associated with
a white forelock, and be caused by a genetic disease called Waardenburg syndrome. In fact, more
than half of congenital hearing loss is inherited. Alternatively, congenital deafness may be due to
a condition or infection to which the mother was exposed duringpregnancy, such as the rubella
virus.
What are the types of hearing loss?
Hearing loss can also be classified based on which portions of the hearing system (auditory
system) are affected. When the nervous system is affected, it is referred to as sensorineural
hearing loss. When the portions of the ear that are responsible for transmitting the sound to the
nerves are affected, it is referred to as conductive hearing loss.
Conditions affecting the cochlea, eighth cranial nerve, spinal cord, or brain cause sensorineural
hearing loss. Examples include:

Meniere's disease,

hearing loss of aging (presbycusis),

nerve injury from syphilis,

hearing loss of unknown cause (idiopathic hearing loss),

nerve tumors and;

drug toxicity (such as aspirin and aminoglycosides).

Conditions that affect the ear canal, eardrum (tympanic membrane), and middle ear lead
to conductive hearing loss. Examples of conductive hearing loss include:

ear wax blocking the ear canal,

otitis media and;

otosclerosis.

What are the symptoms of hearing loss?

Symptoms of hearing loss include mild loss of high frequency hearing, hearing loss associated
with ringing or noises (tinnitus), and complete deafness. Symptoms may develop gradually over
time with many causes of hearing loss.
People who are experiencing hearing loss may refrain from taking part in conversations, may
turn the volume up high on the radio or TV, and may frequently ask others to repeat what they
have said.
What is the treatment for hearing loss?
The treatment of hearing loss depends on its cause. For example:

Ear wax can be removed

Ear infection can be treated with medications

Diseases that cause inflammation of the ear can be treated with medication

Medications that are toxic to the ear can be avoided

Occasionally surgical procedures are necessary

Epilepsy
Introduction

Few experiences match the drama of a convulsive seizure. A person having a severe seizure may
cry out, fall to the floor unconscious, twitch or move uncontrollably, drool, or even lose bladder
control. Within minutes, the attack is over, and the person regains consciousness but is exhausted
and dazed. This is the image most people have when they hear the word epilepsy. However, this
type of seizure - a generalized tonic-clonic seizure -- is only one kind of epilepsy. There are
many other kinds, each with a different set of symptoms.
Epilepsy was one of the first brain disorders to be described. It was mentioned in ancient
Babylon more than 3,000 years ago. The strange behavior caused by some seizures has
contributed through the ages to many superstitions and prejudices. The word epilepsy is derived
from the Greek word for "attack." People once thought that those with epilepsy were being
visited by demons or gods. However, in 400 B.C., the early physician Hippocrates suggested that
epilepsy was a disorder of the brain, and we now know that he was right.
What Is Epilepsy?
Epilepsy is a brain disorder in which clusters of nerve cells, or neurons, in the brain sometimes
signal abnormally. Neurons normally generate electrochemical impulses that act on other
neurons, glands, and muscles to produce human thoughts, feelings, and actions. In epilepsy, the
normal pattern of neuronal activity becomes disturbed, causing strange sensations, emotions, and
behavior, or sometimes convulsions, muscle spasms, and loss of consciousness. During a seizure,
neurons may fire as many as 500 times a second, much faster than normal. In some people, this
happens only occasionally; for others, it may happen up to hundreds of times a day.
More than 2 million people in the United States have experienced an unprovoked seizure or been
diagnosed with epilepsy. For about 80 percent of those diagnosed with epilepsy, seizures can be
controlled with modern medicines and surgical techniques. However, about 25 to 30 percent of
people with epilepsy will continue to experience seizures even with the best available treatment.
Doctors call this situation intractable epilepsy. Having a seizure does not necessarily mean that a
person has epilepsy. Only when a person has had two or more seizures is he or she considered to
have epilepsy.
Epilepsy is not contagious and is not caused by mental illness or mental retardation. Some people
with mental retardation may experience seizures, but seizures do not necessarily mean the person
has or will develop mental impairment. Many people with epilepsy have normal or aboveaverage intelligence. Famous people who are known or rumored to have had epilepsy include the
Russian writer Dostoyevsky, the philosopher Socrates, the military general Napoleon, and the
inventor of dynamite, Alfred Nobel, who established the Nobel Prize. Several Olympic medalists
and other athletes also have had epilepsy. Seizures sometimes do cause brain damage,
particularly if they are severe. However, most seizures do not seem to have a detrimental effect
on the brain. Any changes that do occur are usually subtle, and it is often unclear whether these

changes are caused by the seizures themselves or by the underlying problem that caused the
seizures.
While epilepsy cannot currently be cured, for some people it does eventually go away. One study
found that children with idiopathic epilepsy, or epilepsy with an unknown cause, had a 68 to 92
percent chance of becoming seizure-free by 20 years after their diagnosis. The odds of becoming
seizure-free are not as good for adults or for children with severe epilepsy syndromes, but it is
nonetheless possible that seizures may decrease or even stop over time. This is more likely if the
epilepsy has been well-controlled by medication or if the person has had epilepsy surgery.
What Causes Epilepsy?
Epilepsy is a disorder with many possible causes. Anything that disturbs the normal pattern of
neuron activity -- from illness to brain damage to abnormal brain development -- can lead to
seizures.
Epilepsy may develop because of an abnormality in brain wiring, an imbalance of nerve
signaling chemicals called neurotransmitters, or some combination of these factors. Researchers
believe that some people with epilepsy have an abnormally high level of excitatory
neurotransmitters that increase neuronal activity, while others have an abnormally low level of
inhibitory neurotransmitters that decrease neuronal activity in the brain. Either situation can
result in too much neuronal activity and cause epilepsy. One of the most-studied
neurotransmitters that plays a role in epilepsy is GABA, or gamma-aminobutyric acid, which is
an inhibitory neurotransmitter. Research on GABA has led to drugs that alter the amount of this
neurotransmitter in the brain or change how the brain responds to it. Researchers also are
studying excitatory neurotransmitters such as glutamate.
In some cases, the brain's attempts to repair itself after a head injury, stroke, or other problem
may inadvertently generate abnormal nerve connections that lead to epilepsy. Abnormalities in
brain wiring that occur during brain development also may disturb neuronal activity and lead to
epilepsy.
Research has shown that the cell membrane that surrounds each neuron plays an important role
in epilepsy. Cell membranes are crucial for a neuron to generate electrical impulses. For this
reason, researchers are studying details of the membrane structure, how molecules move in and
out of membranes, and how the cell nourishes and repairs the membrane. A disruption in any of
these processes may lead to epilepsy. Studies in animals have shown that, because the brain
continually adapts to changes in stimuli, a small change in neuronal activity, if repeated, may
eventually lead to full-blown epilepsy. Researchers are investigating whether this phenomenon,
called kindling, may also occur in humans.

In some cases, epilepsy may result from changes in non-neuronal brain cells called glia. These
cells regulate concentrations of chemicals in the brain that can affect neuronal signaling.
About half of all seizures have no known cause. However, in other cases, the seizures are clearly
linked to infection, trauma, or other identifiable problems.
Genetic Factors
Research suggests that genetic abnormalities may be some of the most important factors
contributing to epilepsy. Some types of epilepsy have been traced to an abnormality in a specific
gene. Many other types of epilepsy tend to run in families, which suggests that genes influence
epilepsy. Some researchers estimate that more than 500 genes could play a role in this disorder.
However, it is increasingly clear that, for many forms of epilepsy, genetic abnormalities play
only a partial role, perhaps by increasing a person's susceptibility to seizures that are triggered by
an environmental factor.
Several types of epilepsy have now been linked to defective genes for ion channels, the "gates"
that control the flow of ions in and out of cells and regulate neuron signaling. Another gene,
which is missing in people with progressive myoclonus epilepsy, codes for a protein called
cystatin B. This protein regulates enzymes that break down other proteins. Another gene, which
is altered in a severe form of epilepsy called LaFora's disease, has been linked to a gene that
helps to break down carbohydrates.
While abnormal genes sometimes cause epilepsy, they also may influence the disorder in subtler
ways. For example, one study showed that many people with epilepsy have an abnormally active
version of a gene that increases resistance to drugs. This may help explain why anticonvulsant
drugs do not work for some people. Genes also may control other aspects of the body's response
to medications and each person's susceptibility to seizures, or seizure threshold. Abnormalities in
the genes that control neuronal migration, a critical step in brain development, can lead to areas
of misplaced or abnormally formed neurons, or dysplasia, in the brain that can cause epilepsy. In
some cases, genes may contribute to development of epilepsy even in people with no family
history of the disorder. These people may have a newly developed abnormality, or mutation, in
an epilepsyCan Epilepsy Be Prevented?
Many cases of epilepsy can be prevented by wearing seatbelts and bicycle helmets, putting
children in car seats, and other measures that prevent head injury and other trauma. Prescribing
medication after first or second seizures or febrile seizures also may help prevent epilepsy in
some cases. Good prenatal care, including treatment of high blood pressure and infections during
pregnancy, can prevent brain damage in the developing baby that may lead to epilepsy and other

neurological problems later. Treating cardiovascular disease, high blood pressure, infections, and
other disorders that can affect the brain during adulthood and aging also may prevent many cases
of epilepsy. Finally, identifying the genes for many neurological disorders can provide
opportunities for genetic screening and prenatal diagnosis that may ultimately prevent many
cases of epilepsy.
How Can Epilepsy Be Treated?
Accurate diagnosis of the type of epilepsy a person has is crucial for finding an effective
treatment. There are many different ways to treat epilepsy. Currently available treatments can
control seizures at least some of the time in about 80 percent of people with epilepsy. However,
another 20 percent, about 600,000 people with epilepsy in the United States, have intractable
seizures, and another 400,000 feel they get inadequate relief from available treatments. These
statistics make it clear that improved treatments are desperately needed.
Doctors who treat epilepsy come from many different fields of medicine. They include
neurologists, pediatricians, pediatric neurologists, internists, and family physicians, as well as
neurosurgeons and doctors called epileptologists who specialize in treating epilepsy. People who
need specialized or intensive care for epilepsy may be treated at large medical centers and
neurology clinics at hospitals or by neurologists in private practice. Many epilepsy
treatment centers are associated with university hospitals that perform research in addition to
providing medical care.
Once epilepsy is diagnosed, it is important to begin treatment as soon as possible. Research
suggests that medication and other treatments may be less successful in treating epilepsy once
seizures and their consequences become established.

Essential tremor
Essential tremor (ET) is a nerve disorder characterized by uncontrollable shaking, or "tremors,"
in different parts and on different sides of the body. Areas affected often include the hands, arms,
head, larynx (voice box), tongue, and chin. The lower body is rarely affected.
ET is not a life-threatening disorder, unless it prevents a person from caring for him or herself.
Most people are able to live normal lives with this condition -- although they may find everyday
activities like eating, dressing, or writing difficult. It is only when the tremors become severe that
they actually cause disability.
What Causes Essential Tremor?

The true cause of essential tremor is still not understood, but it is thought that the abnormal
electrical brain activity that causes tremor is processed through the thalamus. The thalamus is a
structure deep in the brain that coordinates and controls muscle activity.
Genetics is responsible for causing ET in half of all people with the condition. A child born to a
parent with ET will have up to a 50% chance of inheriting the responsible gene, but may never
actually experience symptoms. Although ET is more common in the elderly -- and symptoms
become more pronounced with age -- it is not a part of the natural aging process.
Who Gets Essential Tremor?
Essential tremor is the most common movement disorder, affecting up to 10 million people in the
U.S.
While ET can occur at any age, it most often strikes for the first time during adolescence or in
middle age (between ages 40 and 50).
What Are the Symptoms of Essential Tremor?
The primary symptoms associated with essential tremor include:

Uncontrollable shaking that occurs for brief periods of time

Shaking voice
Nodding head
Tremors that worsen during periods of emotional stress
Tremors that get worse with purposeful movement
Tremors that lessen with rest
Balance problems (in rare cases)
The uncontrollable shaking associated with ET is not unique to this condition. Many different
factors or diseases can also cause tremors, including Parkinson's disease, multiple sclerosis,
fatigue after exercise, extreme emotional distress, brain tumors, some prescription drugs,
metabolic abnormalities, and alcohol or drug withdrawal.
Can Essential Tremor Increase the Risk for Other Illnesses?
Essential tremor is linked to other illnesses. Other movement disorders, such as Parkinson's
disease, have been associated with ET. Some reports have also linked ET with migraine
headaches.
Drugs used to treat essential tremor may also increase a person's risk of becoming depressed.

Most experts believe that there is no increased risk for Parkinson's disease for people with ET.
On the other hand, some people diagnosed as having ET are initially incorrectly diagnosed and
subsequently turn out to have Parkinson's disease.
How Is Essential Tremor Diagnosed?
A doctor can usually diagnose essential tremor based on reported symptoms and a complete
neurological exam. There is no specific blood, urine, or other test used to diagnose ET.
As part of the exam, your health care provider may consider other causes of tremor, such
as thyroid disease, excessive caffeine intake, or medication side effects.
How Is Essential Tremor Treated?
Mild essential tremor may not require treatment. However, if ET interferes with your ability to
function or if you find it socially unacceptable, there are treatments that may improve symptoms.
Treatments may include medications or surgery.

Medications: Oral drugs can significantly reduce the severity of essential tremor.
Medications include Inderal, Mysoline, Topamax, and Neurontin. Other drug options include the
tranquilizersKlonopin, Valium, Xanax, and Ativan. Botox injections may also be a treatment
option. This treatment has been effective for vocal and head tremors.
Surgery: Deep brain stimulation (DBS) is a surgical treatment option for people with
severe tremor despite medical therapy. DBS involves surgical implantation of electrical leads
into the thalamus. This is an area deep within the brain that coordinates muscle control that is
thought to be affected in ET.

Friedreich's Ataxia
Friedreichs ataxia (FA) is a debilitating, life-shortening, degenerative neuro-muscular disorder.
About one in 50,000 people in the United States have Friedreich's ataxia. Onset of symptoms can
vary from childhood to adulthood. Childhood onset of FA is usually between the ages of 5 and 15
and tends to be associated with a more rapid progression. Late onset FA (LOFA) can occur
anytime during adulthood. FARA is supporting research that will improve the quality and length
of life for those diagnosed with Friedreich's ataxia and will lead to treatments that eliminate its
symptoms.
Signs and Symptoms

loss of coordination (ataxia) in the arms and legs

fatigue - energy deprivation and muscle loss

vision impairment, hearing loss, and slurred speech

aggressive scoliosis (curvature of the spine)

diabetes mellitus (insulin - dependent, in most cases)

a serious heart condition (enlarged heart - hypertrophic cardiomyopathy)

These symptoms are not present in all individuals with FA, for example diabetes occurs in about
10-20% of individuals with FA. The mental capabilities of people with Friedreich's ataxia remain
completely intact. The progressive loss of coordination and muscle strength leads to motor
incapacitation and the full-time use of a wheelchair. Most young people diagnosed with FA
require mobility aids such as a cane, walker, or wheelchair by their teens or early 20s.
Cause
FA is a genetic disorder. FA patients have gene mutations that limit the production of a protein
called frataxin. Frataxin is known to be an important protein that functions in the mitochondria
(the energy producing factories) of the cell. Frataxin helps to move iron and is involved with the
formation of iron-sulfur clusters, which are necessary components in the function of the
mitochondria and thus energy production. We also know that specific nerve cells (neurons)
degenerate in people with FA, and this is directly manifested in the symptoms of the disease.
Treatments
There are currently no treatments for FA. Patients are monitored for symptom management.
FARA is funding research to find a cure. We believe the treatment era for FA is now! As a result
of great advancements to understand the cause of the disease, new treatments are now emerging.
These treatments address the causes of FA such as gene mutation, frataxin production, iron sulfur
clusters, and mitochondrial function. A full listing of treatment initiatives can be viewed in
FARAs treatment pipeline. Several of these treatments will be in clinical trials which require
patient participation.

Gaucher's Disease
What Is Gaucher's Disease?
This condition causes problems with the way your body gets rid of a certain kind of fat.

With all types of the disease, an enzyme needed to break down this fat in your body doesn't work
right. The fat builds up, especially in your liver, spleen, and bone marrow, causing problems.
There are three main types of Gaucher's disease. Type 1 is the most common. If you have it, your
symptoms may be mild, moderate, or severe. Some people have no symptoms at all. There are
several treatments for type 1.
Type 2 and type 3 are more serious. Type 2 affects the brain and spinal cord. Babies with type 2
usually don't live past age 2. Type 3 also causes damage to the brain and spinal cord, but
symptoms usually show up later in childhood.
There are treatments for Gaucher's disease. Still, living with any chronic illness is stressful.
That's especially true if you're the parent of a child with Gaucher's. Getting help and support are
key to giving your child the best quality of life while facing the challenges and stress this illness
brings.
Gaucher's disease can have many symptoms, including a swollen belly, bruising, and bleeding.
Your blood might not clot well, or you might getanemia. It can also cause bone mineral loss that
leads to pain and easily broken bones.
Its passed along in families -- about 1 in 450 people of Ashkenazi Jewish descent (from Eastern
and Central Europe) have the condition. It's the most common genetic disease that affects Jewish
people.
Causes
Gaucher's disease is inherited. It's caused by a problem with the GBA gene.
You get the disease when both of your parents pass along a damaged GBA gene to you. You can
pass a faulty gene on to your children even if you don't have Gaucher's disease.
Symptoms
Your symptoms depend on what type you have.
Type 1. This is the most common form. It usually doesn't affect thebrain or spinal cord.
Symptoms of type 1 can appear at any time in your life, but they usually show up by the teen
years. Sometimes the disease is mild and you won't notice any symptoms. The warning signs
include:

Easy bruising
Nosebleeds

Fatigue
Enlarged spleen or liver, which makes your belly look swollen
Bone problems like pain, breaks, or arthritis

Type 2. It affects the brain and spinal cord and is very serious. Babies with this form usually
don't live past age 2. The symptoms include:

Slow back-and-forth eye movement

Not gaining weight or growing as expected, called failure to thrive
High-pitched sound when breathing
Seizures
Brain damage, especially to the brain stem
Enlarged liver or spleen
Type 3. This type also affects the brain and spinal cord. The symptoms are similar to type 2, but
they usually show up later in childhood and take longer to get worse.
Perinatal lethal Gaucher's disease. This is the most severe type. Aninfant with this form
usually lives only a few days. These symptoms are overwhelming for a newborn:

Too much fluid in the babys body before or soon after birth
Dry, scaly skin and other skin problems
Enlarged liver and spleen
Severe brain and spinal cord problems
Cardiovascular Gaucher's disease (type 3C). This is rare and mainly affects the heart. Its
symptoms include:

Hardening of the heart valves and blood vessels

Bone disease
Enlarged spleen
Eye problems
Treatment
Treatment depends on what type of Gaucher's disease you have.

Enzyme replacement therapy is one treatment option for people who have type 1 and some with
type 3. It helps make more red blood cells and shrinks an enlarged spleen or liver. Enzyme
replacement therapy medications may include:

Imiglucerase (Cerezyme)
Taliglucerase alfa (Elelyso)
Velaglucerase alfa (VPRIV)
Other treatment options for type 1 are eliglustat (Cerdelga) and miglustat (Zavesca), which are
pills that curb the body's process that forms the fatty materials in people with the enzyme
shortage.
There is no treatment that can stop type 3 from causing damage to the brain. Other treatments
that can help your symptoms include:

Blood transfusions for anemia

Medications to strengthen your bones, prevent fatty buildup, and ease pain
Joint replacement surgery to help you move better
Surgery to remove a swollen spleen
Stem cell transplant to reverse type 1 symptoms. This procedure is complicated and can
cause both short-term and long-term problems, so it is rarely used.

Huntington's disease
Huntington's disease is an incurable, hereditary brain disorder. It is a devastating brain disorder
for which there is no currently 'effective' treatment. Nerve cells become damaged, causing
various parts of the brain to deteriorate. The disease affects movement, behavior and cognition the affected individuals' abilities to walk, think, reason and talk are gradually eroded to such a
point that they eventually become entirely reliant on other people for their care. Huntington's
disease has a major emotional, mental, social and economic impact on the lives of patients, as
well as their families.
It used to be called Huntington's Chorea, because the involuntary movements made by patients
with the disease can appear to be like jerky dancing - "chorea" comes from the Greek
word choreia meaning "dancing". The English word "choreography" also comes from the Greek
word choreia.
Huntington's disease (HD) affects both men and women equally and more commonly appears
during middle-age. According to the Department of Health, UK, there are about 6,000 people in

the UK with the disease. The Huntington's Society of America says 1 in every 10,000 Americans
has the disease - 30,000 people. It is estimated that at least 150,000 other Americans have a 50%
risk of developing HD, while thousands of their relatives carry a degree of risk too.
Prevalence of the disease varies according to ethnic ancestry - people with Asian or African
inheritance have a 1 in 1,000,000 risk of becoming affected, while the risk for Caucasian people
is 70 to 100 times higher.
The J. David Gladstone Institutes, Taube Philanthropies and the Koret Foundation initiated a
groundbreaking research program aimed at preventing, treating, or curing Huntington's disease
by the year 2020.
What are the signs symptoms of Huntington's disease?
Sings and symptoms can appear at any age, but most commonly do so between the ages of 35
and 55 years. They will progressively worsen for ten to twenty years until the patient ultimately
dies.
A sign is what the doctor can detect, such as involuntary movements, or a rash. A symptom is
what the patient tells the doctor, such as dizziness, or insomnia.
How sings and symptoms evolve and which ones appear first may vary from person to person.
Some may develop depression before suffering problems with motor skills.
Initial symptoms may initially be either ignored or attributed to something else for some time by
most patients and their family and friends. This is more likely if people are not aware that
Huntington's disease exists in their family. Symptoms may initially include mood swings and
peculiar behavior.
It is not uncommon for some people to deny they have the condition and take a long time to
come to terms with the diagnosis.
Possible early signs and symptoms
Below is a list of early signs and symptoms which may be relevant in some cases. It is important
to remember these may vary depending on the individual:

Slight uncontrollable movements

Clumsiness

Stumbling

Some slight signs of lack of emotion

Lack of focus, slight concentration problems

Lapses in short-term memory

Depression

Mood changes - this may include antisocial behavior and aggression

Distressing for those who don't know - if family and friends don't know what is going on the
impact on relationships and family life can be demoralizing, distressing and sometimes shocking.
Unexpected temper outbursts directed at a partner from somebody who has hitherto been
regarded as warm, caring and loving is frightening and confusing.
Friends and family may get the impression that an individual with HD is lazy - but it is not the
case. HD typically affects a person's personality in such a way that they come over as
unmotivated, unfocussed, lethargic, and lacking in initiative.
Unnecessarily worrying for those who do know - those who do know they are at risk may
become concerned when they wonder whether an HD sign has emerged. Examples may include
dropping something, suddenly becoming angry, forgetting somebody's name, or stumbling.
These 'signs' are things all of us do from time to time.
In both cases, whether you are aware of the risk, or have no idea what is happening, talking to
your GP (general practitioner, primary care physician) is advisable. The GP may refer the patient
to a neurologist.
What causes Huntington's diseases?
Genes are made up of DNA. They are packaged into strands we call chromosomes. Genes are the
instructions for making any living thing: humans, bacteria, plants, animals, etc. Humans have 23
pairs of chromosomes - 46 in all.
The faulty gene that causes Huntington's disease is found on chromosome number 4. A normal
copy of the gene produces huntingtin, a protein. The faulty gene is larger than it should be and
produces a larger form of huntingtin.
Some of our brain cells are sensitive to the larger form of huntingtin - it undermines their
function and eventually destroys them. Scientists are not sure exactly how this happens. Johns
Hopkins brain scientists have figured out why a faulty protein accumulates in cells everywhere in
the bodies of people with Huntington's disease, but only kills cells in the part of the brain that
controls movement, causing negligible damage to tissues elsewhere. The answer lies in one tiny
protein called "Rhes" that's found only in the part of the brain that controls movement.

A person with the Huntington's gene has one good copy of the gene and one faulty copy of the
gene. His/her child will inherit either the good copy or the faulty one. The child who inherits the
good copy will not develop Huntington's disease, while the child who inherits the faulty copy
will. The child has a 50% chance of inheriting the faulty gene. If the child inherits the faulty
gene, each of his/her children will have a 50% chance of inheriting the faulty gene.
Doctors and scientists refer to the disease as an autosomal dominant disorder - only one copy of
the faulty gene, inherited from either the mother or the father, is necessary to produce the
disease.
A child who does not inherit the faulty gene will not develop HD and cannot pass it on to his/her
children. A child who inherits the faulty gene will develop HD if he/she reaches the age when
symptoms are due to emerge.
3% of people with Huntington's disease apparently have no family history of it. Some of them
were adopted and never knew whether their parents had it. Others may have had a parent with
the faulty gene who died from something else before reaching the age when symptoms would
have emerged. In some cases there may be a new error in the gene - a mutation (it has to start
somewhere).
British scientists found high levels of an inflammation-causing protein called IL-6 in the blood of
affected individuals more than a decade before they were expected to develop the nervous
system symptoms of the Huntington's disease. It has always been presumed that brain deposits of
the mutant protein that causes the disease, called huntingtin, lured an overactive immune
response. But since the immune cells that make IL-6 also make huntingtin, it's possible that
mutant huntingtin might wrongly set these cells on attack mode throughout the body. Early
intervention strategies to suppress the production of IL-6 might thus stave off brain destruction.

Maple Syrup Urine Disease (MSUD)

MSUD is a potentially deadly disorder that affects the way the body breaks down three amino
acids: leucine, isoleucine, and valine. When they're not being used to build a protein, these three
amino acids can either be recycled or broken down for energy. They are normally broken down
by six proteins working together as a complex called BCKD (branched-chain alpha-ketoacid
dehydrogenase).
People with MSUD have a mutation that renders one of the 6 proteins in the complex deficient.
Therefore, they can't break down leucine, isoleucine, and valine. They end up with dangerously

high levels of these amino acids in their blood, causing the rapid degeneration of brain cells and,
if left untreated, even death.
Defects in any of the six subunits of the BCKD protein complex can cause MSUD. The most
common defect is caused by a mutation in a gene on chromosome 19 that encodes the alpha
subunit of the BCKD complex (BCKDHA).
How do people get MSUD?
MSUD is inherited in an autosomal recessive pattern. For a child to get the disease, he or she
must inherit a defective copy of the gene from each parent. If both parents carry the MSUD gene,
each of their children has a 1 in 4 chance of getting the disorder, and a 1 in 2 chance of being a
carrier.
How do doctors diagnose MSUD?
In some states, all babies are screened for MSUD within 24 hours after birth. A blood sample
taken from the baby's heel is analyzed for high leucine levels.

What are the symptoms of MSUD?

There is a classic form of MSUD and several less-common forms. Each form varies in its
severity and characteristics. However, all subtypes of the disorder can be caused by mutations in
any of the 6 genes used to build the BCKD protein complex.
A baby who has the disorder may appear normal at birth. But within three to four days, the
symptoms appear. These may include loss of appetite, fussiness, and sweet-smelling urine. The
elevated levels of amino acids in the urine generate the smell, which is reminiscent of maple
syrup. This is how MSUD got its name. If left untreated, the condition usually worsens. The
baby will have seizures, go into a coma, and die within the first few months of life.
How is MSUD treated?
Treatment involved dietary restriction of the amino acids leucine, isoleucine, and valine. This
treatment must begin very early to prevent brain damage. Babies with the disease must eat a
special formula that does not contain the amino acids leucine, isoleucine, and valine. As the
person grows to adulthood, he or she must always watch their diet, avoiding high-protein foods
such as meat, eggs, and nuts.

If levels of the three amino acids still get too high, patients can be treated with an intravenous
(given through a vein) solution that helps the body use up excess leucine, isoleucine, and valine
for protein synthesis.
Gene therapy is also a potential future treatment for patients with MSUD. This treatmentwould
involve replacing the mutated gene with a good copy, allowing the patient's cells to make a
functional BCKD protein complex and break down the excess amino acids.

Myotonic muscular dystrophy (MMD)

Myotonic muscular dystrophy (MMD) is a form of muscular dystrophy that affects muscles and
many other organs in the body.
The word myotonic is the adjective for the wordmyotonia, an inability to relax muscles at will.
The term muscular dystrophy means progressive muscle degeneration, with weakness and
shrinkage of the muscle tissue.
Myotonic muscular dystrophy often is abbreviated as DM in reference to its Greek
name,dystrophia myotonica. Other names for this disorder include simply myotonic
dystrophy and, occasionally, Steinert disease, after the German doctor who originally described
the disorder in 1909.
(MDA, which covers more than 40 forms of neuromuscular disease, uses the abbreviation
MMD because DM refers to another disease in its program, dermatomyositis.)
What causes MMD?
MMD is divided into two types.
Type 1 MMD (MMD1) occurs when a gene on chromosome 19 called DMPK contains an
abnormally expanded section.
Type 2 MMD (MMD2) is caused by an abnormally expanded section in a gene on chromosome 3
called ZNF9. MMD2 was originally called PROMM, for proximal myotonic myopathy, a term
that has remained in use but is somewhat less common than the term MMD2.
The expanded sections of DNA in these two genes appear to have many complex effects on
various cellular processes.

What are the symptoms of MMD?

MMD causes weakness of the voluntary muscles, although the degree of weakness and the
muscles most affected vary greatly according to the type of MMD and the age of the person with
the disorder.
Myotonia, the inability to relax muscles at will, is another feature of MMD. For example, it may
be difficult for someone with MMD to let go of someone's hand after shaking it.
As the disease progresses, the heart can develop an abnormal rhythm and the heart muscle can
weaken. The muscles used for breathing can weaken, causing inadequate breathing, particularly
during sleep.
In addition, in type 1 MMD (see Types of MMD), the involuntary muscles, such as those of the
gastrointestinal tract, can be affected. Difficulty swallowing, constipation and gallstones can
occur. In females, the muscles of the uterus can behave abnormally, leading to complications in
pregnancy and labor.
The development of cataracts (opaque spots in the lenses of the eyes) relatively early in life is
another characteristic of MMD, in both type 1 and type 2.
Overall intelligence is usually normal in people with MMD, but learning disabilities and an
apathetic demeanor are common in the type 1 form. In congenital MMD1, which affects children
from the time of birth, there can be serious impairment of cognitive functioning. These children
also may have problems with speech, hearing and vision.
Generally, the earlier MMD1 begins, the more profound the symptoms tend to be. In general,
MMD2 has a better overall prognosis than MMD1. The symptoms are often relatively mild and
progress slowly. MMD2 rarely occurs during childhood, and there is no known congenital-onset
form.

What is neurofibromatosis?
Neurofibromatosis (NF) is a genetic neurological disorder that can affect the brain, spinal cord,
nerves and skin. Tumors, or neurofibromas, grow along the body's nerves or on or underneath the
skin. Scientists have classified NF into two distinct types: neurofibromatosis type 1 (NF1) and
NF2. NF1, formerly known as von Recklinghausen's NF, is the more common of the types. It
occurs in approximately 1 in 4,000 births. NF2, also referred to as bilateral acoustic NF, central
NF or vestibular NF, occurs less frequently- 1 in 40,000 births. Occurences of NF1 and NF2 are
present among all racial groups and affect both sexes equally. The tumors arise from changes in

the nerve cells and skin cells. Tumors also may press on the body's vital areas as their size
increases. NF may lead to developmental abnormalities and/or increased chances of having
learning disabilities. Other forms of NF, where the symptoms are not consistent with that of NF1
or NF2, have been observed. A rare form of NF is schwannomatosis. However, the genetic cause
of this form of NF has not been found.
What are the symptoms of neurofibromatosis?
Symptoms for neurofibromatosis type 1 include:

Presence of light brown sports (caf-au-lait) on the skin.

Appearance of two or more neurofibromas (pea-sized bumps) that can grow either on the
nerve tissue, under the skin or on many nerve tissues.

Manifestation of freckles under the armpits or in the groin areas.

Appearance of tiny tan clumps of pigment in the iris of the eyes (Lisch nodules).

Tumors along the optic nerve of the eye (optic glioma).

Severe curvature of the spine (scoliosis).

Enlargement or malformation of other bones in the skeletal system.

Symptoms for NF1 vary for each individual. Those that are skin-related are often present at birth,
during infancy and by a child's tenth birthday. From ages 10 to 15, neurofibromas may become
apparent. Symptoms such as caf-au-lait spots, freckling and Lisch nodules pose minimal or no
health risk to a person. Though neurofibromas are generally a cosmetic concern for those with
NF1, they can sometimes be psychologically distressing. For 15 percent of individuals with NF1,
the symptoms can be severely debilitating. Neurofibromas can grow inside the body and may
affect organ systems. Hormonal changes at puberty and/or even pregnancy may increase the size
of neurofibromas. Nearly 50 percent of children with NF1 have speech problems, learning
disabilities, seizures and hyperactivity. Less than one percent of those affected with NF1 may
have malignant tumors and may require treatment.
Symptoms for neurofibromatosis type 2 include:

Tumors along the eighth cranial nerve (schwannomas).

Meningiomas and other brain tumors.

Ringing noises inside the ear (tinnitus), hearing loss and/or deafness.

Cataracts at a young age.

Spinal tumors.

Balance problems.

Wasting of muscles (atrophy).

Individuals with NF2 develop tumors that grow on the eighth cranial nerves and on the vestibular
nerves. These tumors often cause pressure on the acoustic nerves, which result in hearing loss.
Hearing loss may begin as early as an individual's teenage years. Tinnitus, dizziness, facial
numbness, balance problems and chronic headaches may also surface during the teenage years.
Numbness may also occur in other parts of the body, due to spinal cord tumors.
The rare form of NF, schwannomatosis, which was recently identified, does not develop on the
eighth cranial nerves, and does not cause hearing loss. It causes pain primarily, and in any part of
the body. Though schwannomatosis may also lead to numbness, weakness or balance problems
like NF1 or NF2, the symptoms are less severe.
How is neurofibromatosis diagnosed?
Neurofibromatosis is diagnosed from a combination of findings. For children to be diagnosed
with NF1, they must show at least two of the aforementioned symptoms associated with NF1. A
physical examination by a doctor familiar with the disorder is usually performed. Doctors may
use special lamps to examine the skin for caf-au-lait spots. Doctors may also rely on magnetic
resonance imaging (MRI), X-rays, computerized tomography (CT scan) and blood tests to detect
defects in the NF1 gene.
For NF2, doctors will pay close attention to hearing loss. Hearing tests as well as imaging tests
are used to look for tumors in and around the auditory nerves, the spinal cord or the brain.
Audiometry and brainstem auditory evoked response tests can help determine whether the eighth
cranial nerve is functioning properly. Family history of NF2 is also a key focal area for
diagnosis.
Genetic testing is also used to diagnose NF1 and NF2. Testing conducted before birth (prenatal)
is helpful to identify individuals who have a family history of the disorder, but do not yet have
the symptoms. Still, gene tests have no way of predicting the severity of NF1 or NF2. Genetic
testing is performed by either direct gene mutation analysis and/or linkage analysis. Mutation
analysis looks to identify the particular gene changes that cause NF. A linkage analysis is useful
if the mutation analysis does not provide enough conclusive information. With at linkage
analysis, blood tests from multiple family members are taken to track the chromosome that carry
the disease-causing gene through two or more generations. Linkage testing is around 90 percent
accurate in determining whether individuals have NF. Mutation analysis is 95 percent accurate in
finding a mutation for NF1, and 65 percent accurate for NF2.
How is neurofibromatosis treated?
Though there is no cure for either NF1 or NF2, there are ways to treat the effects the disease.
Surgery may be helpful in removing tumors, though there is a risk of the tumors regenerating.

For optic gliomas, treatment may include surgery and/or radiation. For scoliosis, treatment may
include surgery or back braces. For symptoms associated with NF2, surgery may be a viable
option, however not without complications that could result in additional loss of hearing or
deafness. Hearing aids are ineffective when parts of the auditory nerve are removed. A
breakthrough in treatment became available recently to NF2 patients, when the Food and Drug
Administration approved an Auditory Brainstem Implant [fda.gov] for those who have parts of
their auditory nerve removed and have suffered from subsequent hearing loss. The implant
transmits sound signals to the brain directly and allows people to hear certain sounds and
speech . Radiation treatment, may also help relieve symptoms associated with NF2.

Parkinson's disease

Parkinson's disease is the second most common neurodegenerative disorder and the most
common movement disorder. It is characterized by progressive loss of muscle control, which
leads to trembling of the limbs and head while at rest, stiffness, slowness, and impaired balance.
As symptoms worsen, it may become difficult to walk, talk, and complete simple tasks.
The progression of Parkinson's disease and the degree of impairment vary from individual to
individual. Many people with Parkinson's disease live long productive lives, whereas others
become disabled much more quickly. Premature death is usually due to complications such as
falling-related injuries or pneumonia.
Most individuals who develop Parkinson's disease are 60 years of age or older. Since overall life
expectancy is rising, the number of individuals with Parkinson's disease will increase in the
future. Adult-onset Parkinson's disease is most common, but early-onset Parkinson's disease
(onset between 21-40 years), and juvenile-onset Parkinson's disease (onset before age 21) also
exist.
Descriptions of Parkinson's disease date back as far as 5000 BC. Around that time, an ancient
Indian civilization called the disorder Kampavata and treated it with the seeds of a plant
containing therapeutic levels of what is today known as levodopa. Parkinson's disease was
named after the British doctor James Parkinson, who in 1817 first described the disorder in great
detail as "shaking palsy."
What causes Parkinson's disease?

A substance called dopamine acts as a messenger between two brain areas - the substantia nigra
and the corpus striatum - to produce smooth, controlled movements. Most of the movementrelated symptoms of Parkinson's disease are caused by a lack of dopamine due to the loss of
dopamine-producing cells in the substantia nigra. When the amount of dopamine is too low,
communication between the substantia nigra and corpus striatum becomes ineffective, and
movement becomes impaired; the greater the loss of dopamine, the worse the movement-related
symptoms. Other cells in the brain also degenerate to some degree and may contribute to nonmovement related symptoms of Parkinson's disease.
Although it is well known that lack of dopamine causes the motor symptoms of Parkinson's
disease, it is not clear why the dopamine-producing brain cells deteriorate. Genetic and
pathological studies have revealed that various dysfunctional cellular processes, inflammation,
and stress can all contribute to cell damage. In addition, abnormal clumps called Lewy bodies,
which contain the protein alpha-synuclein, are found in many brain cells of individuals with
Parkinson's disease. The function of these clumps in regards to Parkinson's disease is not
understood. In general, scientists suspect that dopamine loss is due to a combination of genetic
and environmental factors.
What are the symptoms of Parkinson's disease?
The primary symptoms of Parkinson's disease are all related to voluntary and involuntary motor
function and usually start on one side of the body. Symptoms are mild at first and will progress
over time. Some individuals are more affected than others. Studies have shown that by the time
that primary symptoms appear, individuals with Parkinson's disease will have lost 60% to 80% or
more of the dopamine-producing cells in the brain. Characteristic motor symptoms include the
following:

Tremors: Trembling in fingers, hands, arms, feet, legs, jaw, or head.Tremors most often
occur while the individual is resting, but not while involved in a task. Tremors may worsen
when an individual is excited, tired, or stressed.
Rigidity: Stiffness of the limbs and trunk, which may increase during movement.
Rigidity may produce muscle aches and pain. Loss of fine hand movements can lead to
cramped handwriting (micrographia) and may make eating difficult.
Bradykinesia: Slowness of voluntary movement. Over time, it may become difficult to
initiate movement and to complete movement. Bradykinesia together with stiffness can also
affect the facial muscles and result in an expressionless, "mask-like" appearance.
Postural instability: Impaired or lost reflexes can make it difficult to adjust posture to
maintain balance. Postural instability may lead to falls.
Parkinsonian gait: Individuals with more progressive Parkinson's disease develop a
distinctive shuffling walk with a stooped position and a diminished or absent arm swing. It

may become difficult to startwalking and to make turns. Individuals may freeze in midstride and appear to fall forward while walking.
Secondary symptoms of Parkinson's disease
While the main symptoms of Parkinson's disease are movement-related, progressive loss of
muscle control and continued damage to the brain can lead to secondary symptoms. These vary
in severity, and not every individual will experience all of them. Some of the secondary
symptoms include:

anxiety, insecurity, and stress

confusion, memory loss, and dementia (more common in elderly individuals)

constipation

depression

difficulty swallowing and excessive salivation

diminished sense of smell

increased sweating

male erectile dysfunction

skin problems

slowed, quieter speech, and monotone voice

urinary frequency/urgency

Refsum Disease
What causes Refsum disease?
The peroxisome is responsible for the breakdown of certain branched chain fatty acids. A
common branched chain fatty acid, phytanic acid, is shown below. It is different from the straight
chain fatty acid shown above in that it has branches of carbon groups off the main carbon
chain (branches are colored in blue).

Phytanic acid is a component of our diet, and therefore needs to be digested properly. The
peroxisome is responsible for the breakdown of phytanic acid, and impairment of this specific
function results in Refsum disease.
What are the clinical symptoms of Refsum disease?
Patients with Refsum disease do not generally show any obvious defects at birth, and growth and
development appears normal. Initial symptoms will generally appear by age 20, although patients
have been known who do not display symptoms until around age 50. The initial complaints
usually involve vision problems, and/or weakness in the arms and legs. The disease is
progressive, although there can be periods of unexplained remission. Below is a list of the most
common symptoms of Refsum disease. We have included the clinical terms as well as a
description of their meaning.
o

o
o

o
o
o
o

Retinitis pigmentosa: Retinitis pigmentosa is a disease of the eye, resulting from

degeneration of a part of the eye called the retina. It affects night vision and peripheral vision,
and eventually can lead to blindness.
Peripheral polyneuropathy: Peripheral polyneuropathy is the term for dysfunction of the
nerves outside of the spinal cord. Symptoms may include numbness, weakness, burning pain,
and loss of reflexes.
Deafness: loss of hearing
Cerebellar ataxia: Ataxia is wobbliness. Cerebellar ataxia refers to the fact that the defect
is in a specific part of the brain (the cerebellum), and the incoordination and unsteadiness is due
to the brains failure to regulate the bodys posture, as well as the strength and direction of the
bodys movements.
Anosmia: loss of the sense of smell
Papillary abnormalities: abnormality of the pupils of the eye
Nystagmus: rapid, involuntary, rhythmic eye movements
Icthyosis: Icthyosis is a noninflammatory scaliness of the skin. These symptoms can
range anywhere from scaliness of the palms and soles of the feet to scaliness on the trunk of the
body.
Epiphyseal dysplasia: The epiphysus is the growth area at the end of a bone, while
dysplasia means abnormal formation. This means that patients with Refsum disease often have
shortened limbs.
What are the possible treatments for Refsum disease?
Nearly all phytanic acid is obtained from the diet, which means that dietary control is an option
for Refsum disease. Patients are advised to keep consumption of phytanic acid below 10 mg/day
(the normal intake is approximately 100 mg/day). Sources of high levels of phytanic acid include

beef, lamb, full cream, milk, butter, and cheese. It is important to be careful to maintain weight,
because loss of weight can cause release of stored phytanic acid from fat tissues. This results in
an increase in plasma phytanic acid levels, and can lead to a worsening of symptoms. If there is
difficulty reducing levels of phytanic acid in the plasma, sometimes plasmapheresis (replacement
of the plasma) can help.

Rett syndrome

Rett syndrome is a rare, but severe brain disorder that affects girls. It's usually discovered in the
first two years of life, and a child's diagnosis with Rett syndrome can feel overwhelming.
Although there's no cure, early identification and treatment may help girls and families who are
affected by Rett syndrome.
Who Gets Rett Syndrome?
Rett syndrome is a genetic that affects girls almost exclusively. It's rare -- only about one in
10,000 to 15,000 girls will develop the condition.
In most cases of Rett syndrome, a child develops normally in early life. Between 6 and 18
months of age, though, changes in the normal patterns of mental and social development begin.
What Are the Symptoms of Rett Syndrome?
Although it's not always detected, a slowing of head growth is one of the first events in Rett
syndrome. Loss of muscle tone is also an initial symptom. Soon, the child loses any purposeful
use of her hands. Instead, she habitually wrings or rubs her hands together.
Around 1 to 4 years of age, social and language skills deteriorate in a girl with Rett syndrome.
She stops talking and develops extreme social anxiety and withdrawal or disinterest in other
people.
Rett syndrome also causes problems with muscles and coordination. Walking becomes awkward
as girls develop a jerky, stiff-legged gait. A girl with Rett syndrome may also have uncoordinated
breathing andseizures.
What Causes Rett Syndrome?

Most children with Rett syndrome have a mutation in a particular gene on the X chromosome.
Exactly what this gene does, or how its mutation leads to Rett syndrome, isn't clear. It's believed
that the single gene may influence many other genes involved in development.
Although Rett syndrome seems to be genetic, the faulty gene is almost never inherited from the
parents. Rather, it's a chance mutation that happens in the girl's own DNA. No Rett syndrome
risk factors have been identified, other than being female. There is no known method for
preventing Rett syndrome.
When boys develop the Rett syndrome mutation, they die shortly after birth. Because boys have
only one X chromosome (instead of the two girls have), the disease is more serious, and quickly
fatal.
Treatments for Rett Syndrome
There are treatments available for Rett syndrome that focus on helping a girl live the best life she
can with the condition. Physical therapy can help improve mobility; speech therapy may help
somewhat with language problems; and occupational therapy helps girls perform daily activities
-- like bathing and dressing -- independently.
Experts believe that therapy can help girls with Rett syndrome and their parents. Although a
"normal" life may not be possible, some improvement can be expected with therapy.
Participating in activities -- including school -- and improved social interaction are sometimes
possible.
Medicines can treat some of the problems with movement in Rett syndrome. Medication can also
help control seizures. Unfortunately, there is no cure for Rett syndrome

Tuberous sclerosis complex (TSC)

Tuberous sclerosis complex (TSC) is a genetic disorder affecting cellular differentiation,

proliferation, and migration early in development, resulting in a variety of hamartomatous
lesions that may affect virtually every organ system of the body.
The best-known cutaneous manifestation of TSC is adenoma sebaceum, which often does not
appear until late childhood or early adolescence. This lesion is an angiofibroma (ie, cutaneous
hamartoma) and is not related to excessive sebum or acne. Flat, reddish macular lesions develop
first, which can be mistaken for freckles early on. See the image below.

Signs and symptoms

Findings in TSC include the following:

Neurologic findings: Abnormal neurologic findings result from the location, size, and
growth of tubers and the presence of subependymal nodules (SENs) and subependymal giant
cell astrocytomas (SEGAs)
Cutaneous findings: The best-known cutaneous manifestation of TSC is adenoma
sebaceum, which often does not appear until late childhood or early adolescence
Cardiac findings: Cardiac involvement is usually maximal at birth or early in life; it may
be the presenting sign of TSC, particularly in early infancy; 50-60% of individuals with TSC
have evidence of cardiac disease, mostly rhabdomyomas.
Ophthalmic findings: At least 50% of patients have ocular abnormalities; some studies
have reported a prevalence as high as 80%; these lesions are actually retinal astrocytomas that
tend to become calcified over time
Pulmonary findings: Prospective and retrospective studies have found cystic pulmonary
abnormalities in as many as 40% of women with TSC
Renal findings: Renal manifestations of TSC are the second most common clinical
feature; 4 types of lesions can occur: autosomal dominant polycystic kidney disease lesions,
isolated renal cyst(s), angiomyolipomas (AMLs), and renal cell carcinomas
Dental findings: Pitting of the dental enamel is invariably present in the permanent teeth
of patients with TSC [1] ; gingival fibromas occur in 70% of adults with TSC, in 50% of children
with mixed dentition (primary and permanent teeth), and in 3% of children with only primary
teeth
Gastrointestinal findings: Hamartomas and polyposis of the stomach, intestine, and colon
may occur
Hepatic findings: Hepatic cysts and hepatic AMLs, typically asymptomatic and
nonprogressive, have been reported in as many as 24% of patients with TSC, with a marked
female predominance (female-to-male ratio 5:1)
Skeletal findings: Sclerotic and hypertrophic lesions of bone may be found incidentally
on radiography performed for other indications
See Clinical Presentation for more detail.
Diagnosis
Laboratory studies
Laboratory studies are performed as indicated clinically to identify genetic mutations associated
with TSC, monitor anticonvulsant treatment, identify idiosyncratic or dose-related adverse

effects, and identify or monitor underlying renal or pulmonary disease. Diagnosis should be
possible in most cases using established clinical criteria. Molecular genetic testing is useful in
uncertain or questionable cases, as well as for prenatal diagnosis and for screening family
members of an affected individual.
Imaging studies
The following 3 imaging studies are usually undertaken in patients with TSC:

Computed tomography scanning or magnetic resonance imaging of the brain: Performed

to identify SEGAs before obstructive hydrocephalus occurs; they also identify the extent and
number of cortical tubers present [2]
Renal ultrasonography: Performed to assess change in AMLs or cysts, in the hope that
this will allow operative intervention prior to the development of renal failure
Echocardiography: Performed as part of the baseline evaluation in a patient with newly
diagnosed or suspected TSC
Additional tests
Other tests used in the assessment of patients with TSC include the following:

Electroencephalography: Should be performed in patients with TSC in whom seizures are

suspected; follow-up electroencephalography is performed as clinically indicated
Electrocardiography: Baseline electrocardiography is recommended for all patients newly
diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their
presenting symptom

Von Hippel-Lindau Syndrome

What is von Hippel-Lindau syndrome?
Von Hippel-Lindau syndrome (VHL) is a hereditary condition associated with
hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye. The eye
tumors are also called retinal angiomas. People with VHL also have an increased risk of
developing clear cell renal cell carcinoma, which is a specific type of kidney cancer;
andpheochromocytoma, which is a tumor of the adrenal gland. Kidney cysts, which are closed
sacs usually filled with fluid; pancreatic cysts, epididymal cystadenomas, which are tumors near
a mans testicles; and endolymphatic sac tumors, which are tumors of the ear that may cause
hearing loss; are also features of VHL.

What causes VHL?

VHL is a genetic condition. This means that the cancer risk and other features of VHL can be
passed from generation to generation in a family. The gene associated with VHL is also
called VHL. A mutation, meaning alteration in the VHL gene gives a person an increased risk of
developing kidney cancer and other symptoms of VHL. Nearly everyone who has VHL
syndrome has an identifiable VHL mutation.
How is VHL inherited?
Normally, every cell has two copies of each gene: one inherited from the mother and one
inherited from the father. VHL follows an autosomal dominant inheritance pattern, in which a
mutation happens in only one copy of the gene. This means that a parent with a gene mutation
may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a
child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother,
sister, or parent of a person who has a mutation also has a 50% chance of having the same
mutation.
Options exist for couples interested in having a child when they know that one of them carries a
gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation
Genetic Diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization
(IVF). It allows people who carry a specific known genetic mutation to have children who do not
carry the mutation. A womans eggs are removed and fertilized in a laboratory. When the
embryos reach a certain size, one cell is removed and is tested for the hereditary condition in
question. The parents can then choose to transfer embryos which do not have the mutation. PGD
has been in use for over a decade, and more recently has been used for several hereditary cancer
predisposition syndromes. For more information, talk with an assisted reproduction specialist at
a fertility clinic.
How common is VHL?
It is estimated that about one in 30,000 people has VHL. About 20% of people with VHL do not
have any family history of the condition. They have a de novo, meaning anew mutation in
the VHL gene.
How is VHL diagnosed?
VHL is suspected when a person has:

Multiple hemangioblastomas of the brain, spinal cord, or eye, or

One hemangioblastoma and kidney cysts, pancreatic cysts, pheochromocytoma,

or kidney cancer, or
In young patients, VHL is also suspected with multiple bilateral clear cell renal cell
carcinoma.

If a person has a family history of VHL, he or she is suspected of also having VHL if the person
has any one symptom, such as hemangioblastoma, kidney or pancreatic cysts,
pheochromocytoma, or kidney cancer. Genetic testing for mutations in the VHL gene is available
for people suspected to have VHL. Nearly all people with VHL will be found to have the genetic
mutation once tested.
What are the estimated cancer risks associated with VHL?
The risk of kidney cancer in families with VHL is estimated to be about 40%.
Would the treatment of kidney cancer change if I have VHL?
In general, treatment for kidney cancer is similar regardless of whether a patient has VHL.
However, there is some evidence about specific VHL considerations regarding two types of
treatment: surgery and targeted therapy. For a person with VHL and kidney cancer, surgery for a
kidney tumor is generally considered when a tumor reaches three centimeters (cm) in size.
Targeted therapy is a treatment that targets the cancers specific genes, proteins, or the tissue
environment that contributes to cancer growth and survival. Anti-angiogenesis therapy is a type
of targeted therapy used in kidney cancer treatment. It is focused on stopping angiogenesis,
which is the process of making new blood vessels. Because a tumor needs the nutrients delivered
by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to starve the
tumor. For people with VHL, there is emerging research showing that an anti-angiogenic drug
called sunitinib (Sutent), which is classified as a tyrosine kinase inhibitor (TKI), may be effective
against kidney cancer. Learn more about this approach in the general Kidney Cancer Treatment
Options section of this website.

Reference:

http://www.healthline.com/health/adrenoleukodystrophy#Symptoms4

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