Anencephaly is a cephalic disorder that results from a neural tube defect that occurs when the cephalic (head)

end of the neural tube fails to close, usually between the 23rd and 26th day of pregnancy, resulting in the absence of a major portion of the brain, skull, [1] and scalp. Children with this disorder are born without a forebrain, the largest part of the brain consisting mainly of the cerebral hemispheres (which include the neocortex, which is responsible for higher-level cognition, i.e., thinking). The remaining brain tissue is often exposednot covered by bone or skin.
[2]

Most babies with this genetic disorder do not survive birth.

Signs

and symptoms

An anencephalic newborn

The National Institute of Neurological Disorders and Stroke (NINDS) describes the presentation of this condition as follows: "A baby born with anencephaly is usuallyblind, deaf, unconscious, and unable to feel pain. Although some individuals with anencephaly may be born with a main brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining consciousness. Reflex actions such as breathing and responses to sound or touch occur."
[2]

Causes
The cause of anencephaly is disputed. Generally, neural tube defects do not follow direct patterns of heredity, though there is some indirect evidence of inheritance,
[3]

and recent animal models indicate a

[4]

possible association with deficiencies of the transcription factor TEAD2.

[5]

Studies show that a woman

who has had one child with a neural tube defect such as anencephaly has about a 3% risk of having another child with a neural tube defect.

It is known that women taking certain medications for epilepsy and women with insulin-dependent diabetes have a higher risk of having a child with a neural tube defect."Anencephaly". Genetics Home Reference. National Institutes of Health. 22 August 2011. Retrieved 28 August 2011. Genetic counseling is usually offered to women at a higher risk of having a child with a neural tube defect to discuss available testing. Recent studies have shown that the addition of folic acid to the diet of women of child-bearing age may significantly reduce, although not eliminate, the incidence of neural tube defects. Therefore, it is recommended that all women of child-bearing age consume 0.4 mg of folic acid daily,
[2]

especially those
[citation needed]

attempting to conceive or who may possibly conceive, as this can reduce the risk to 0.03%.

It

is not advisable to wait until pregnancy has begun, since by the time a woman knows she is pregnant, the critical time for the formation of a neural tube defect has usually already passed. A physician may prescribe even higher dosages of folic acid(4 mg/day) for women who have had a previous pregnancy with a neural tube defect.
[original research?]

Anencephaly and other physical and mental deformities have also been blamed on a high exposure to such toxins as lead, chromium, mercury, and nickel.
[6]

Relation to genetic ciliopathy

Until recently, medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely varying set of medical symptoms that are clinically visible in the disorders. Anencephaly is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelleswhich are present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease,nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome, and some forms of retinal degeneration.
[7]

Diagnosis

Ultrasound image of fetus with anencephaly

Anencephaly can often be diagnosed before birth through an ultrasound examination. The maternal serum alpha-fetoprotein (AFP screening)
[8]

and detailed fetal ultrasound

[9]

can be useful for screening for

neural tube defects such as spina bifida or anencephaly.

Prognosis
This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (June 2011) There is no cure or standard treatment for anencephaly and the prognosis for patients is death. Most anencephalic fetuses do not survive birth, accounting for 55% of non-aborted cases. If the infant is not stillborn, then he or she will usually die within a few hours or days after birth from cardiorespiratory arrest.
[2][10]

In almost all cases, anencephalic infants are not aggressively resuscitated because there is no chance of the infant ever achieving a conscious existence. Instead, the usual clinical practice is to offer hydration, nutrition, and comfort measures and to "let nature take its course". Artificial ventilation, surgery (to fix any co-existing congenital defects), and drug therapy (such as antibiotics) are usually regarded as futile efforts. Clinicians and medical ethicists may view the provision of nutrition and hydration as medically futile.

Epidemiology

In the United States, approximately 1 out of 150,000 to 200,000 babies is born with anencephaly each year. Research has suggested that, overall, female babies are more likely to be affected by the disorder.
[11]

Anencephaly

Anencephaly is the absence of a large part of the brain and the skull. Causes Anencephaly is one of the most common neural tube defects. Neural tube defects are birth defects that affect the tissue that grows into the spinal cord and brain. Anencephaly occurs early in the development of an unborn baby. It results when the upper part of the neural tube fails to close. Why this happens is not known. Possible causes include environmental toxins and low intake of folic acid by the mother during pregnancy. Anencephaly occurs in about 1 out of 10,000 births. The exact number is unknown, because many of these pregnancies result in miscarriage. Having one infant with this condition increases the risk of having another child with neural tube defects. Symptoms Absence of the skull Absence of the brain (cerebral hemispheres and cerebellum) Facial feature abnormalities Heart defects

Exams and Tests A pregnancy ultrasound is done to confirm the diagnosis. The ultrasound may reveal too much fluid is in the uterus. This condition is called polyhydramnios. Other tests that may be done on the pregnant mother: Amniocentesis (to look for increased levels of alpha-fetoprotein) Alpha-fetoprotein level (increased levels suggest a neural tube defect) Urine estriol level

A pre-pregnancy serum folic acid test may also be done.

http://www.nlm.nih.gov/medlineplus/ency/article/001580.htm

Sadly, there is no medical treatment for anencephaly. Due to the lack of development of babies' brains, about 75 percent of infants are stillborn and the remaining 25 percent of babies die within a few hours, days or weeks after delivery. Care focuses on providing emotional support to your family. Our social workers will offer you a network of support groups with families going through similar issues. Many families find consolation knowing their child has not been forgotten by those who cared for him or her and that there are others who share in their grief. Also, we may recommend genetic counseling for parents to discuss the risk of recurrence in a future pregnancy as well as vitamin therapy (a prescription for folic acid) that can decrease the recurrence for ONTDs. Extra folic acid, a B vitamin, if taken one to two months prior to conception and throughout the first trimester of pregnancy, has been found to decrease the reoccurrence of ONTDs, for couples who have had a previous child with an ONTD.

What is anencephaly
Anencephaly is a congenital birth defect (from the Latin congenitus, born with). It begins to develop right at the start of life in the womb. The word anencephaly means without an encephalon, the encephalon being the set of nervous center contained in the brain. This is not an entirely accurate definition: whilst a child with anencephaly is indeed born without a scalp, without a vault of the cranium, without meninges, without either brain hemisphere and without a cerebellum, the child is nevertheless usually born with part of its cerebral trunk, brainstem (Mller 1991). Almost 75% of babies with anencephaly born at term survive their birth. The life expectancy of those who survive is only a few hours or days (Jaquier 2006). Approximately 20 percent of affected infants have additional congenital anomalies (Botto 1999).

What role does the brainstem play?

Together with the spinal chord, it controls many of the bodys unconscious functions, such as the heart beat, and it coordinates most voluntary movements.

Occurrence:
Approximately one child for every 1000 births (Central Europe). This rate varies according to populations. (Sadler, T.W. 2005)

Children most affected:

Anencephaly affects more girls than it does boys.

Can it be treated?
Unfortunately, there is no known treatment for a child with an anencephaly.

Manifestation:

Anencephaly belongs to the family of neural tube defects. A neural tube defect (NTD) is a congenital malformation which occurs between the 20th and 28th day after conception (Sadler 1998). The cells of the neural plate make up the foetus nervous system. In normal development, they fold back onto themselves in order to create what is called the neural tube, which then becomes the back bone and the spinal cord. After a number of transformations, the superior pole eventually becomes the brain. One can liken this process to a coin whose edges merge at its centre. In the case of an NTD, the neural tube is unable to close completely. Anencephaly occurs when the head end of the neural tube fails to close. Infants with this disorder are born without a scalp or cerebellum. Their meninges, both hemispheres of the brain and the vault of the cranium/skull are also missing, though they usually do have part of the brain stem. The remaining brain tissue is protected only by a thin membrane. The infant can be blind and has no, or very few, reflexes. About of anencephalic babies die at birth; those who survive have a life expectancy of a few hours or days (Jaquier 2006).

What causes an anencephaly?

It is still not known what causes anencephaly. It is probably triggered by a combination of genetic and environmental factors (Sadler 2005). We nevertheless know that taking Folic Acid can prevent anencephaly. Some medicines (the pill, valproic acid, antimetabolic drugs and others) lower Folic Acid levels, hence taking them increases the risk of giving birth to a child with anencephaly (Sadler, 2005). Chromosomal abnormalities, single-gene mutations, and teratogenic causes are indentified in fewer than 10 percent of affected infants (Holmes 1976)

Is it caused by anything the parents did?

No, no one is to blame for the baby having anencephaly

Life expectancy:
About 25% of anencephalic children who live to the end of the pregnancy die during delivery; 50% have a life expectancy of between a few minutes and 1 day, 25% live up to 10 days (Jaquier 2006) Get more information: Report about the birth and life of babies with anencephaly

At what point can an anencephaly be diagnosed?

Anencephaly can be reliably diagnosed at 11-14 weeks of gestation by ultrasound scan (Johnson SP et al. 1997) AFP levels can be measured via a maternal serum screening test (blood test). If levels are high, there is a risk that the child may be suffering from an NTD. Further tests must then be carried out (ultrasound scan or amniocentesis) to determine whether there really is a problem. Screening must take place between the 15th and the 20th week, the best time being the 16th week.

What is AFP?
The foetus, through its urine, releases into the amniotic liquid a protein called alphafetoprotein (AFP). The exposed tissue of a child suffering from an NTD release greater quantities of AFP into the amniotic liquid. The AFP then enters the mothers blood stream through the placenta and can hence be measured.

Is the diagnosis reliable?

Anencephaly is a malformation which is very easy to see on an ultrasound scan. If a qualified doctor has made an ultrasound scan diagnosis after the 16th week, the likelihood of a misdiagnosis is minimal. A positive maternal serum screening test, however, simply shows that there is a higher risk that the baby has Trisomy 21 or 18, or an neural tube defect. Most women who test positive give birth to healthy babies. Additional tests must be carried out to determine whether the baby is suffering from one of those ailments.

Might the mothers health be jeopardised?

No. Pregnancy is unaffected. In around a quarter of cases, too much amniotic liquid is produced (polyhydramnios). This is due to the fact that the child does not have the reflexes to enable it to swallow the amniotic liquid. If the volume of liquid is excessive, it can cause discomfort for the mother. Labour may be triggered prematurely, or waters may break. An amniocentesis can then be carried out to reduce the amount of liquid (amniodrainage); Amniotic liquid is removed with a syringe, thus providing the mother with temporary relief.

What does an anencephalic child look like?

The body of an anencephalic child is entirely unaffected. However, the vault of the cranium is missing from the eye-brows up. Half-way up to the back of the head is usually covered by skin and hair. Vivid dark red neural tissue covered by nothing more than a thin membrane can be seen through an opening in the head. The size of this opening varies considerably from one child to another. The eyeballs can protrude because of a malformation of the eyesockets, which is why anencephalic children are sometimes pejoratively described as looking like frogs.

Illustration used with the permission of CDC Centers for Disease Control and Prevention

Can an anencephalic child sense or do anything?

Doctors will tell you that an anencephalic child can neither see nor hear, nor feel pain, that he or she is a vegetable. However, that does not match up with the experience of many families who have had an anencephalic child. The brain is affected to varying degrees, according to the child; the brain tissue can reach different stages of development. Some children are able to swallow, eat, cry, hear, feel vibrations (loud sounds), react to touch and even to light. But most of all, they respond to our love: you dont need a complete brain to give and receive love- all you need is a heart!

What happens during the birth of an anencephalic child?

Normally, the baby helps to trigger labour with its pituitary gland and suprarenals (glands of the kidneys). However, these are either missing or their development has been stunted in anencephalic children, hence labour does not always begin spontaneously. As a result, many women ask that labour be induced at the end of their pregnancy. As the vault of the cranium is missing, it is important that the waters do not break for as long as possible during labour so that they can exert the necessary pressure on the cervix for it to dilate. If it is possible to keep the waters intact, the birth of an anencephalic child will happen in almost the same way as if the mother were giving birth to a healthy child, and will take as long. The experience of mothers of anencephalic children has shown that the artificial breaking of waters significantly reduces the chances of the baby being born alive (Jaquier 2006).

Can anencephalic children be organ donors?

Theoretically they can. In practice, there are certain problems. The science of organ grafting in newly-born babies is incipient; its medium-term results are not well known, whereas its long-term results are not known at all. The organs of an anencephalic child can only be removed if the child has been certified dead. However, the criteria that define cerebral death cannot usually be applied to children under 7 days old. Before cerebral death is confirmed, the organs of such children may become so damaged that they are unfit for organ-donation. Anencephalic children do not have a rear brain but they do have a forebrain which usually functions normally at birth. The forebrain dies slowly and other organs may die in the intervening period of time. It has been observed that clinical cerebral death (complete absence of reactions and reflexes and absence of spontaneous breathing) almost always occurs after the heart has begun to fail. Therefore anencephalic children would only rarely be able to donate organs. In some countries / states, the heart valves can be removed for use in a later transplant. The problems mentioned above are less relevant because the valves can be removed up to 8 hours after the death of the child and are frozen until a recipient is found. Find Links about organ donation in anencephalic infants.

What is the rate of recurrence?

In most cases it is an isolated anomaly and it is very unlikely that it should occur again in the same family. Statistically, the rate of recurrence for a woman who has already had an anencephalic child is 4%.

Can anencephaly be prevented?

For some time now, the aetiology of Neural Tube Defects has cited diet and environmental factors. Clinical studies have confirmed that taking a vitamin called Folic Acid reduces the

risk of developing a Neural Tube Defect. If all women of child-bearing age took 0.4 mgs of Folic Acid every day before conception and at least until the end of the first term of pregnancy, 50 to 70% of potential cases of anencephaly and Spina Bifida could be prevented (Ceizel and Dudas, 1992). Learn more about theprevention of neural tube defects.

What research is being done?

The National Institute of Neurological Disorders and Stroke conducts and supports a wide range of studies that explore the complex mechanisms of normal brain development. The knowledge gained from these fundamental studies provides the foundation for understanding how this process can go awry and, thus, offers hope for new means to treat and prevent congenital brain disorders including neural tube defects such as anencephaly. The Duke Center for Human Genetics is currently conducting a genetic study called "The Hereditary Basis of Neural Tube Defects" to determine the causes of anencephaly and other NTDs. By studying families with anencephaly and other NTDs, they hope to identify the genes that contribute to the development of the neural tube. They hope this research will eventually lead to more accurate genetic counseling and risk assessment, improved treatments, better prevention methods, and possibly, a cure. More information and how to participate

PONTI Study (Prevention Of Neural Tube defects by Inositol)

If you have had a pregnancy affected by a neural tube defect and planning another pregnancy, you might want to know about an important research project that aims to prevent neural tube defects with a vitamin treatment. UK only.

References:
Botto LD et al, 1999. Neural-Tube Defects. N England J Med 341:1509-1519 Czeizel AE, Dudas I. 1992. Prevention of first occurence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 327:1832-1835 Holmes LB, Briscoll SG, Atkins L. 1976. Etiologie heterogeneity of neural-tube defects. N Engl J Med 1976;294:365-369 Jaquier M, Klein A, Boltshauser E., 2006. Spontaneous pregnancy outcome after prenatal diagnosis of anencephaly, BJOG 2006; 113:951-953 Johnson SP, Sebire NJ, Snijders RJM, Tunkel S, Nicolaides KH. Ultrasound screening for anencephaly at 10-14 weeks of gestation. Ultrasound Obstet Gynecol 1997;9:14. Mller F, O'Rahilly R, 1991. Development of Anencephaly and Its Variants. The American Journal of Anatomy 190:193-218 (1991) Sadler TW, 1998. Mechanisms of neural tube closure and defects. Ment Retard Dev Disabil Res Rev 1998;4:247-53 Sadler TW. 2005. Embryology of Neural Tube Development. American Journal of Medical Genetics Part C 135C:2-8

Last updated September 09, 2010