Down`s Syndrome

A 36-year-old woman with little prenatal care delivers a 3900-g girl.They

came to your private clinic to review the child . they noticed the infant
has decreased tone. On examination you noticed some dysmorphic
features
Expected findings

small head circumference

brachycephalic ( flat occiput )
silky hair
Flat face
Upward slanting palpebral fissures
Epicanthic folds
White speckles in the iris (Brushfield
spots)
short depressed nasal bridge
Small external ear with over folded
helix
small oral cavity with protruded
fissured tongue

:Other suspected features looking for

Short broad hands with single semian crease wide gap between 1st and 2nd toes of
the feet poorly developed genitalia
Investigate
Karyotyping-1
CBC -2
Thyroid profile ( governmental) -3
Echocardiography -4

Abdominal U/S -5
Plain x-ray if suspected penumonia -6
Chromosomes must be sent for urgent analysis. This is to confirm the clinical suspicions,
Look for mosaicism (_1 per cent) that might alter the prognosis and to exclude a translocation.
If a translocation is identified, parental chromosomes must be analysed in case
.One is a carrier with a high risk of recurrence
In newborns with suspected Down Syndrome, at least two potentially life-threatening
Conditions must be addressed. Approximately 50% of ds infants have cardiac
Defectsmost commonly an endocardial cushion defect (60%), ventricular
Septal defect (vsd, 32%), and tetralogy of fallot (6%). A cardiology
Consultation and echocardiogram usually are indicated.
approximately 12% of ds infants have intestinal (usually duodenal) atresia, some presenting
with a history of polyhydramnios. All ds infants have hypotonia and sometimes
Slower feeding. Should an infant with presumed ds develop persistent
Vomiting after feeds (especially if bilious), an upper gi study likely will reveal
The characteristic double-bubble pattern of duodenal atresia; surgical Intervention is
warranted
Management
diagnosis and management of complications : surgical consultaion if cardiac or gut -1
anomalies or other anomalies . refer to ophthalmologist if eye abnormalities suspected
follow-up : for growth and development (motor-social-speech-emotional-behavioral) -2
regular hearing and vision testing
special schools for rehabilitation and education -3

Klinefelter Syndrome
A 13 years old tall boy his school performance below average .he seems
to be more immature than his old brother . presented to you by
gynecomastia. on examination his extremities are longer than expected
and
Expected findings

male 47XXY
disproportionate tall stature ( tall
legs )
gynecomastia
small tests
absence of 2ry sexual charachters
IQ ratio usually in the normal range
but may have educational and
psychological problems
Investigate
Full hormonal evaluation high plasma level
of FSH high plasma level of LH high
plasma level of Estradiol level and low
plasma level of Testosterone

Treatment
Androgen therapy
Androgen therapy is the most important aspect of treatment. Testosterone replacement
should begin at puberty, around age 12 years, and the dose should increase until it is sufficient to
maintain age-appropriate serum concentrations of testosterone, estradiol, follicle-stimulating hormone
(FSH), and luteinizing hormone (LH).
o
Androgen therapy is used to correct androgen deficiency, to provide appropriate virilization,
and to improve psychosocial status. Regular testosterone injections can promote strength and facial hair
growth; build a more muscular body type; increase sexual desire; enlarge the testes; improve mood,
self-image, and behavior; and protect against precocious osteoporosis.
o

Dose : 12 years 50-200 mg IM every 2 weeks for 4-6 months

not recommended before 12 years

: Trade name

by CID -1 deep i.m. amp.Testosterone

L.E 6

oenanthate 250mg.

Cidotest
on

7.5

by Misr - 3 amp.Testosterone+Vit. E

Testone-

L.E

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by Nile - 1 amp. Testosterone 250mg I.M

Testonon

Turner`s Syndrome (syndrome of gonadal dysgensis)

A 10 days old female baby presented by lymphedema .
on examination there`s webbing of the neck
Expected findings
female 45 XO
low posterior hairline
webbed neck and extra skin
wide-set nipples
discolored spots on skin
swollen hands and feet

In Adolescence there`s 1ry amenorrhea due to the ovary is

steak of Connective tissue leading to failure of development of
2ry sexual characters with normal mentality . more than 2/3 of
cases pass undiagnosed until puberty due to subtle signs

Investigate

karyotype analysis is required for diagnosis of Turner syndrome, in order to exclude -1

.mosaicism
2- Both LH and FSH may be elevated in untreated patients younger than 4 years.
Gonadotropins are later suppressed to normal or near-normal levels, only to rise to
menopausal levels after age 10 years.
3- Because of the high prevalence of hypothyroidism in Turner syndrome, obtain
thyroid function tests at diagnosis.
Treatment
1-girls with TS are relatively growth hormone resistant but they do benefit from
growth hormoe treatment which can increase their final height by about 5 cm time of
treatment not established
They also need hormone replacement in the form of Estrogen to induce puberty
2-Estrogen (Ethinyloestradiol) is usually started at age 12-15 years. Treatment better
to be started at 15 years the growth will be better .These can be cycled in a 3-weeks
on, 1-week off regimen (dose :0.1 mcg/kg/d) Tablet size 2mcg after 6-18 months;
progestin can be added later. Transdermal estrogens are associated with physiologic
estrogen levels, and may be preferred treatment, if tolerated.
3-Antihypertensive should be added

Ambiguous genitalia
A mid-wife calls the NICU asking urgent review of ababy
born 10 minutes ago although baby have penis there`s
no obvious scrotum and they can`t feel the testes . Is it A
boy or A girl ? there`s prolonged Capillary refill time with
signs of Shock and mild Respiratory distress
Expected findings

According to Karyotype

the presence of at least one palpable

testicle suggest the Y chromosome and its
absence from scrotum,labia or inguinal region
suggest it`s female with salt losing congenital
adrenal hyperplasia until proved otherwise
consider pelvic U/S & Genitogram it`ll help
to identify the gonads and uterus if present
Karyotype will differentiate it into 3 major
categories
measure serum electrolytes , LH ,
Testosterone ,DHT
ACTH stimulation test and HCG stimulation
test

1-Genetic male XY ( Undervirilized male )

hypothalamic pituitary defect-1
Low LH,T & DHT
Androgen insensitivity-2
High LH, T & DHT
5Alpha Reductase deficinecy -3
Normal LH,T But Low DHT
High LH and low T+DHT requires gonadal biopsy to assess for steak gonads ,
rudimentary Mullerian structures or absent Wolffian structures

Genetic Female XX ( Virilized female )-2

Congenital adrenal hyperplasia: single most common cause of ambiguous genitalia
21alpha hydroxylase deficiency is the most severe and presents at about two weeks
of age with salt wasting and are at risk for adrenal crisis. Like in our case
hydroxy progesterone should be assessed it will markedly elevated (>50NG/ML) 17
the baby should be resuscitated with fluids initially with hydrocortisone then on oral
hydrocortisone and fludrocortisones
The Mother SHOULD be evaluated for ovarian or adrenal or CAH
Hydrocortisone dose 20mg/m2/day PO Q8h ( approximately 1mg/kg/dose every 8
hours ) Fludrocortisone dose 0.1mg - 0. 3mg /day/PO
by Pharmacia/Eipico -1 Via
Hydrocortisone 100mg.

3.5 L
E

4 LE

12 L

SoluCorte

by Amoun - 20
tab.Fludrocortisone 0.1mg.

Cortilon

byMerck/MinaPharm - 30 tabs .
Fludrocortisone 0.1mg.

3-Chromosomal Abnormalities
Autosomal trisomies or deletion sex chromosomes trisomies- mosaic
abnormalities

Astonin-H

Precocious puberty
True precocious puberty : development of 2ry sexual characters (breast development
pubic hair and axillary hair) before age of 8 y in females or 9 y in males with
increase size and activity of gonads it`s central gonadotpin dependent involving
Hypthalamo-pituitary gonadal activation
Pseudo precocius puberty : development of one of 2ry sexual characters before age of
8 y in females or 9 y in males it`s peripheral non gonadotropin dependent doesn`t
involove Hypothalamo pituitary gonadal activation
Etiology of pseudo precocious puberty

premature thelarche in girls-1

My 4years old baby is developing breasts this had been since birth but
increasingly she was on no medications by examination her height 117 (98%
percentile) breast develoment was Tanner stage 2
Just ask about pubic hair (sign of true precocious puberty for that age )
Reassurance of the mother tell her this is benign condition due to secretion of
Estrogen and it regress spontaneously

Gynecomastia in boys-2
Samy is 15 years old presented to you with history of gynecomastia 18
months ago no history of galactorrhea he is shy of this testes about 15ml
volume his weight 78kg and height 169cm
You should measure Testosterone (7.2-21.5 Nmol/L) and Estradiol level (30-130Pmol/L)

a-The most common cause for gynecomastia in boys is pubertal gynecomastia it

occurs in about 60% of Boys it`s benign ,Idiopathic condition and you`ll find 1-3cm
round free mobile tender mass
b-Klienfelter syndrome can be associated with Gynecomastia but there`s small
testicles
c-Rare Estrogen secreting tumors as feminizing adrenal tumor or Leydig cell tumor of
the testis there will be abnormal Estradiol levels
d-Prolactinoma gynecomastia also but there`s galactorrhea
e-Rare breast tumors
f- Drugs as Estrogen and Spironolactone
Just Reassurance and advice weight loss plastic sergury if needed for psychological
purpose

premature adrenarche-3
Simple development of sexual hair due to increased production of adrenal Hormones
no other sign of puberty
Etiology of True precocious puberty
My 5 years old daughter developed Breast and pubic hair she is tall stature
have body odor
This 5 years old girl has signs of mainly central True Precocious puberty investigations
are needed for that girl
A gonadotropin releasing hormone stimulation test measure the time and peak value
for LH & FSH After intravenous injection of GnRH (elevated level of LH >8 U/L is
diagnostic)
Consider Pelvic U/S
Consider MRI for all boys >9y with development of 2ry sexual characters (mainly
tumors) and All girls below 6y
Majority of cases >90% in girls Idiopathic
2ry causes in girls and boys as Organic brain lesion may occurs (tumorshydrocephalus-trauma-radiotherapy)
Treatment
For idiopathic causes Progestins work by providing feedback suppression of pituitary gonadotropin
secretion. They lack significant androgenic or estrogenic activity relative ineffectiveness in
reversing rapid advancement of skeletal maturation the breast will shrink about 1 year when
puberty is timing discontinue the drug Dose: 5-10mg oral daily dose
Provera

.by Pharmacia- 24 tab. Medroxyprogesterone5 mg

20 LE

1ry Amenorrhea workup

Short stature
A6 years old boy was seen in outpatient clinic His parents
complained that he was the shortest boy in his class
DDx
familial short stature Normal variant-1
constitutional delay of growth normal variant-2
Genetic (Down-Turner-Achondroplasia-Mucopolysacharidosis- Noonan`s and Brader -3
willi syndrome) discussed before
Gland (decrease growth hormone- juvenile hypothyroidism-Adrenal insufficiency) -4
Systemic illness ( chronic renal failure- chronic hepatic disease- T.B- Chronic -5
hemolytic anaemia- malabsorption as Celiac disease ) discussed later
Psychological & Nutritional (decrease feeding )-6
Intrauterine dwarfism ( Small for gestational age)-7
Drugs as steroids and ADHD medicine -8

Approach to a case of short stature

A)History
Family history of short stature or delayed puberty Genetic history history of any
systemic illness nutritional and psychological history history of medications

B)Calculate mid-parental height

For boys = ( paternal height in inches + maternal height in inches / 2 ) + 2.5 inches
For Girls = ( paternal height in inches + maternal height in inches / 2 ) - 2.5 inches

C)Physical Examination
Plot height and weight of the child on growth charts
? Is there`s any dysmorphic features ? is there`s any signs of chronic illness

D)Exclude Turner Syndrome

E)Assess Growth rate and Bone age

If growth rate > 4cm/year it`s familial

If growth rate < 4cm/year + normal bone age it`s familial
If growth rate > 4cm/year + delayed bone age it`s constitional or Russell silver
syndrome

Russell silver syndrome

there`s short length
triangular face
prominent forehead
narrow chin and small jaw
down turned corners of the mouth
unusuall curving of the fifth finger

If growth rate < 4cm/year + delayed bone age search for pathological causes
( Order TSH-T3-T4 IGF-1 MRI )
IF high TSH consider 1ry Hypothyroidism-1
IF low or normal TSH and low T4 persumed hypopituitarism consult Endocrinologist-2
IF normal Thyroid function and normal IGF-1 and normal MRI Trial of GH therapy-3
(somatropin)
IF abnormal MRI consult Endocrinologist and neurosurgery -4
Treatment

constitutional delay treated by Testosterone depot 50-100mg I.M /monthly for 6 -1

months it will stimulate growth without unduly advancing the bone age it makes
growth spurt earlier
Trade names : page 3
2-1ry hypothyroidism treated by L-Thyroxine <12year : 5 mg/kg/day (100 mg/day)
>12year : 3 mg/kg/day ( 150mg/day)
Trade
Eltroxin
by GSK
LE 7
Thyroxin 50 Micro gm.
.tab 100
Once daily
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T4-Thyro
.tabs 100
Thyroxin 50 MICROgm.
Once daily
Russell silver syndrome treated by Growth hormone (somatropin) still under trials -3
Dose :0.2- 0.24 I.U/kg body weight, 3 times a week S.C
Long term treatment of children who have growth failure due to lack of endogenous
.growth hormone
Treatment of children who have growth failure associated with chronic renal
.insufficiency up to the time of renal transplantation
.Patients suffering from Turners syndrome (Gonadal digenesis)
Somatropin 4I.U

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N.B: Familial and constitutional are most common causes of short stature
Disproportionate short stature (improper US/LS) occurs in
Hypothyroidism,Rickets and Skeletal Dysplasia
Lower segment from symphysis pubis to the floor
Upper segment (total height Lower segment )

Tall Stature
Amr is 10 years old boy came to you with his mother whom worried
about being tall his father is tall 1.93m his mother is 1.66 m on
examination his height is 1.58m (>99th centile) wt 35kg (75th centile)
He has long tapering fingers & his thumb when completely opposed
within the clenched hand projects beyond ulnar border chest is free
except pectus excavatum there`s late systolic murmur on the apex

Approach to tall stature

SDS Standard Deviation Score

DDx of tall stature
1-Disproportionate
A)Marfan Sy. Our case
B)Homocystinuria clinical features similar to Marfan Syndrome distinction
established by urinary amino acid analysis
C)Klinefelter Sy. Discussed before
2-Proportionate
A)Familial Reassurance
B)Healthy Simple Obesity Reassurance
C)Precocious Puberty Discussed before
D)Increase Growth Hormone Discussed before
E)Hyperthyroidism Discussed before

Obesity
Samir is 7 years old boy presented to you because he is over weight .
his father is average weight .His father is average weight . His father
say the boy diet is generally good but his grandmother spoil him He
does sport twice a week at school He snores every night but his
parents not noticed any sleep apnea He is on no medications . By
examination his height is 125cm (75th centile) and his weight is 38.7
kg (>99.6th centile)
BMI=weight in (kg)/height in (m2) =24.8 kg/m2 plot it on BMI charts

If BMI > 91ST centile (overweight) BMI>98th centile (Obese)

Any case of obesity must be examined for
- Dysmorphic features ( Down sy. Prader willi Sy. Laurence Moon Biedl
Sy Klinefelter Sy.)
- Abdominal stretch marks ( cushing`s )
- Goiter
- Blood pressure as a complication
- Tonsils gap for obstructive sleep apnea as a complication
DDx
1-Simple obesity
2-Genetic one or both parents is obese
3-Syndromes ( Down sy. Prader willi Sy. Laurence Moon Biedl Sy Klinefelter
Sy.)
4-Endocrinal ( Hypothyroidism Cushing`s Growth Hormone deficiency)
5-Drugs (Steroids Na valproate)
Treatment
1-Dietetic input is very important
2-Encourage exercise for 60min/day
3-Discourage Sedentary activities as playing games

4-treatment of complications as (Hypertension sleep apnea by tonsillectomyDiabetes or heart failure if present )

5-Drugs as Orlistat is reserved for childrens > 12 years
40 L
by GNP/Penta
E
Pharma
Regimax
30 caps.
Orlistat 120mg.
90 L
E

32 L
E
65 L
E

by Sigma
30 caps.
Orlistat 120 mg.
by Pharaonia
10 caps.
by EVA Pharm
10 Cap.

N.B: Children who are obese and short tend to have underlying pathology as
Endocrine disorder

Orlistat

Orlisma
rt

An Odd shaped Head

Yasin is 5 month old boy . his mother noted abnormal head shape he`s
born at 38 weeks by forceps delivery there`s no any medical problem
How to deal
1-measure weight 7.5kg (50th centile) length 67cm (75th centile) head
circumference 43.5cm (50th centile)

2-face appearance : is it symmetrical and there`s no dysmorphic features ? (no

syndromes)
3-Examine sutures of the skull : is there`s any premature closure of the sutures
N.B:Skull deformity in infants divided into 3 broad categories positional
deformity isolated craniostenosis and craniostenosis associated with other
syndromes (Apert Sy.- Crouzon Sy.- Jackson weiss syndrome)
You should assess for craniostenosis if present do Skull x-ray it will show
(silver beaten appearance) ,MRI to detect ( hydrocephalus , subdural
hematoma or space occupying lesion ) and consider neurosurgery
If there`s no craniostenosis identify Dolicocephaly or positional plagiocephaly
Dolicocephaly (long head)
It`s usually positional specialy in preterm and commonly benign as a result of
lateral positioning of the head it`s resolve by 3 months but if there`s no history
of prematurity consider craniostenosis

Plagicephaly (slanting head)

Positional plagiocephaly there`s 1-

Unilateral Lambdoid

symmetrical molding with no effect on the

brain function resolved in 2 months after
adjusting sleep position & stretching neck
muscles ( by using toys to get the baby looking
for difficult side )
2- Asymmetrical molding the ear is displaced
anteriorly and all sutures are open

synostenosis
Assymetrical (trapezoid)
shaped head the ear is
diplaced posteriorly and
the lambdoid suture is
closed

All cases proved to be Craniostenosis should be referred to Neurologist for treatment

plan

syndrome: large head with

forehead short arms & legs low
Q - complex syndactyly
rouzon syndrome : maxillary
ypoplasia fused maxilla sutures
widely spaced eyes protruding
ye balls

Apert
prominent
I
C
h

Macrocephaly
Nijar is 2 months old her mother claims she has large head.on examination
Head circumference =41cm (>97th centile) for that age
Any case of macrocephaly focus on the following during history taking and physical
examination
History focus on possible causes of hydrocephalus (prematurity-meningitis- intra
ventricular hemorrhage)
Family history of (metabolic disease benign familial macrocephaly)
Physical examination
measure head circumference -1
examine fontanelle for for bulging-2
eye for papilledema and sunsetting-3
(suggest Hydrocephalus increase intra cranial tension mass lesion tumors 1.2.3 )
systemic signs of congestive heart failure suggest intracranial vascular-4
malformation
organomegaly suggest metabolic disease-5
Dysmorphic features suggest chromosomal disease-6
Work-up
MRI
IF Abnormal (hydrocephalus increase intra cranial tension- mass lesion tumorsvascular malformation ) consult neurosurgery
If Normal assess development over time
normal milestones this is Benign familial condition -1
loss of milestones suspect neurodegenerative disorder consult neurologist -2
Causes and DDx of macrocephaly
Cranial
Intracranial
Benign familial macrocephaly
Hydrocephalus
Rickets
Increase intra cranial tension
Achondroplasia
Space occupying lesions
Chronic hemolytic anaemia
Tumors
Vascular malformation
Metabolic
chromosomal

Microcephaly

Salma is 3 days old girl her mother claims she has small head cleft palate
extra finger umbilical hernia. On examination Head circumference 30cm
(below 3rd centile) he doesn`t startle to loud voice there`s dysmorphic
features (microcephaly microphthalmia polydactyly cleft lip and palate
umbilical hernia and rocket bottom feet

Microcephaly
Any case of microcephaly must be take good history that focus on pregnancy
,perinatal complications family history of microcephaly and developmental milestone
And examined carefully for tone,reflexes,dysmorphic syndromes and neurocutanous
stigmata
And investigated according to associated features (MRI-Chromosomal study TORCH
screen )
If MRI Abnormal consider neurosurgery
If MRI Normal assess for development
If normal development observation mainly familial
If abnormal development consider TORCH Neurodegenrative disorder Autosomal
dominant syndromes there will be other associated features
Aetiology and DDx of Microcephaly /Mental retardation/Cerebral palsy
1ry
familial (Autosomal recessive)-1
Autosomal dominant (Down,Edward,Cri du chat & Patu syndrome)-2
2ry
Prenatal causes : Infection TORCH,Irradiation,Toxins as fetal alcohol syndrome -1
Natal causes: Hypoxic Ischaemic Injury-2
Postnatal: Kernicteurs,Intracranial hemorrhage,C.N.S infection (meningitis & -3
encephalitis)

Cri Du Chat Syndrome

also known as 5p- (5p minus) syndrome, is a

chromosomal condition that results when a piece
of chromosome 5 is missing. Infants with this
condition often have a high-pitched cry that
.sounds like that of a cat
Those having this syndrome usually have very distinct
features
microcephaly-1
usually round face-2
small chin-3
eyes are very far apart-4
folds of skin over their eyes-5
small nose bridge-6
feeding problems due to difficulty of swallowing-7
severe speech and motor delay (hypotonia)-8
hyperactivity and aggressive behaviour-9

Mental Retardation