Down`s SyndromeA 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 Investigate1-Karyotyping2- CBC3- Thyroid profile ( governmental)4- Echocardiography5- Abdominal U/S6- Plain x-ray if suspected penumonia

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 caseOne is a carrier with a high risk of recurrence.In newborns with suspected Down Syndrome, at least two potentially life-threateningConditions must be addressed. Approximately 50% of ds infants have cardiacDefectsmost commonly an endocardial cushion defect (60%), ventricularSeptal defect (vsd, 32%), and tetralogy of fallot (6%). A cardiologyConsultation 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 sometimesSlower feeding. Should an infant with presumed ds develop persistentVomiting after feeds (especially if bilious), an upper gi study likely will reveal

The characteristic double-bubble pattern of duodenal atresia; surgical Intervention is warranted

Management1-diagnosis and management of complications : surgical consultaion if cardiac or gut anomalies or other anomalies . refer to ophthalmologist if eye abnormalities suspected 2-follow-up : for growth and development (motor-social-speech-emotional-behavioral) regular hearing and vision testing 3-special schools for rehabilitation and education

Klinefelter SyndromeA 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 InvestigateFull hormonal evaluation high plasma level of FSH high plasma level of LH high plasma level of Estradiol level and low plasma level of Testosterone

TreatmentAndrogen 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). 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.Dose : 12 years 50-200 mg IM every 2 weeks for 4-6 months not recommended before 12 yearsTrade name :Cidoteston byCID-1 deep i.m. amp.Testosterone oenanthate 250mg.6 L.E

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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

Investigate1- karyotype analysis is required for diagnosis of Turner syndrome, in order to exclude 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.Treatment1-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 puberty2-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 genitaliaA 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 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

According to Karyotype1-Genetic male XY ( Undervirilized male )Low LH,T & DHT1-hypothalamic pituitary defect

High LH, T & DHT2-Androgen insensitivity

Normal LH,T But Low DHT3- 5Alpha Reductase deficinecy

High LH and low T+DHT requires gonadal biopsy to assess for steak gonads , rudimentary Mullerian structures or absent Wolffian structures

2-Genetic Female XX ( Virilized female )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 17 hydroxy progesterone should be assessed it will markedly elevated (>50NG/ML) 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/POSoluCortef

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3-Chromosomal AbnormalitiesAutosomal trisomies or deletion sex chromosomes trisomies- mosaic abnormalities

Precocious pubertyTrue 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 activationPseudo 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 activationEtiology of pseudo precocious puberty1-premature thelarche in girlsMy 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 spontaneously2-Gynecomastia in boysSamy 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 massb-Klienfelter syndrome can be associated with Gynecomastia but there`s small testiclesc-Rare Estrogen secreting tumors as feminizing adrenal tumor or Leydig cell tumor of the testis there will be abnormal Estradiol levelsd-Prolactinoma gynecomastia also but there`s galactorrheae-Rare breast tumorsf- Drugs as Estrogen and SpironolactoneJust Reassurance and advice weight loss plastic sergury if needed for psychological purpose3-premature adrenarcheSimple development of sexual hair due to increased production of adrenal Hormones no other sign of pubertyEtiology of True precocious pubertyMy 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 girlA 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/SConsider MRI for all boys >9y with development of 2ry sexual characters (mainly tumors) and All girls below 6yMajority of cases >90% in girls Idiopathic 2ry causes in girls and boys as Organic brain lesion may occurs (tumors-hydrocephalus-trauma-radiotherapy)TreatmentFor 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 dose20LEbyPharmacia-24 tab. Medroxyprogesterone5 mg. Provera

1ry Amenorrhea workup

Short statureA6 years old boy was seen in outpatient clinic His parents complained that he was the shortest boy in his class

DDx1-familial short stature Normal variant2-constitutional delay of growth normal variant3-Genetic (Down-Turner-Achondroplasia-Mucopolysacharidosis- Noonan`s and Brader willi syndrome) discussed before4-Gland (decrease growth hormone- juvenile hypothyroidism-Adrenal insufficiency)5-Systemic illness ( chronic renal failure- chronic hepatic disease- T.B- Chronic hemolytic anaemia- malabsorption as Celiac disease ) discussed later6-Psychological & Nutritional (decrease feeding )7-Intrauterine dwarfism ( Small for gestational age)8-Drugs as steroids and ADHD medicineApproach to a case of short statureA)HistoryFamily history of short stature or delayed puberty Genetic history history of any systemic illness nutritional and psychological history history of medicationsB)Calculate mid-parental heightFor boys = ( paternal height in inches + maternal height in inches / 2 ) + 2.5 inchesFor Girls = ( paternal height in inches + maternal height in inches / 2 ) - 2.5 inchesC)Physical ExaminationPlot 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 SyndromeE)Assess Growth rate and Bone age

If growth rate > 4cm/year it`s familialIf growth rate < 4cm/year + normal bone age it`s familialIf growth rate > 4cm/year + delayed bone age it`s constitional or Russell silver syndrome Russell silver syndromethere`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 )1-IF high TSH consider 1ry Hypothyroidism2-IF low or normal TSH and low T4 persumed hypopituitarism consult Endocrinologist3-IF normal Thyroid function and normal IGF-1 and normal MRI Trial of GH therapy (somatropin)4-IF abnormal MRI consult Endocrinologist and neurosurgery Treatment1-constitutional delay treated by Testosterone depot 50-100mg I.M /monthly for 6 months it will stimulate growth without unduly advancing the bone age it makes growth spurt earlierTrade names : page 32-1ry hypothyroidism treated by L-Thyroxine 12year : 3 mg/kg/day ( 150mg/day) Trade7LEbyGSK100 tab.EltroxinThyroxin 50 Micro gm. Once daily

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3-Russell silver syndrome treated by Growth hormone (somatropin) still under trialsDose :0.2- 0.24 I.U/kg body weight, 3 times a week S.CLong 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).

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

Tall StatureAmr 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 ScoreDDx of tall stature1-DisproportionateA)Marfan Sy. Our caseB)Homocystinuria clinical features similar to Marfan Syndrome distinction established by urinary amino acid analysisC)Klinefelter Sy. Discussed before2-Proportionate A)Familial ReassuranceB)Healthy Simple Obesity ReassuranceC)Precocious Puberty Discussed beforeD)Increase Growth Hormone Discussed beforeE)Hyperthyroidism Discussed before

ObesitySamir 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 DDx1-Simple obesity2-Genetic one or both parents is obese3-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)Treatment1-Dietetic input is very important2-Encourage exercise for 60min/day3-Discourage Sedentary activities as playing games4-treatment of complications as (Hypertension sleep apnea by tonsillectomy- Diabetes or heart failure if present )5-Drugs as Orlistat is reserved for childrens > 12 yearsRegimax

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

An Odd shaped HeadYasin 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 suturesN.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 neurosurgeryIf 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- 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 openUnilateral Lambdoid synostenosisAssymetrical (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 Apert syndrome: large head with prominent forehead short arms & legs low IQ - complex syndactylyCrouzon syndrome : maxillary hypoplasia fused maxilla sutures widely spaced eyes protruding eye balls

MacrocephalyNijar 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 examinationHistory focus on possible causes of hydrocephalus (prematurity-meningitis- intra ventricular hemorrhage)Family history of (metabolic disease benign familial macrocephaly)Physical examination1-measure head circumference 2-examine fontanelle for for bulging3-eye for papilledema and sunsetting( 1.2.3 suggest Hydrocephalus increase intra cranial tension mass lesion tumors)4-systemic signs of congestive heart failure suggest intracranial vascular malformation5-organomegaly suggest metabolic disease6-Dysmorphic features suggest chromosomal diseaseWork-upMRIIF Abnormal (hydrocephalus increase intra cranial tension- mass lesion tumors- vascular malformation ) consult neurosurgeryIf Normal assess development over time 1-normal milestones this is Benign familial condition2- loss of milestones suspect neurodegenerative disorder consult neurologistCauses and DDx of macrocephalyIntracranialHydrocephalus Increase intra cranial tensionSpace occupying lesionsTumorsVascular malformationMetabolic chromosomalCranialBenign familial macrocephalyRicketsAchondroplasiaChronic hemolytic anaemia

MicrocephalySalma 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

MicrocephalyAny case of microcephaly must be take good history that focus on pregnancy ,perinatal complications family history of microcephaly and developmental milestoneAnd examined carefully for tone,reflexes,dysmorphic syndromes and neurocutanous stigmataAnd investigated according to associated features (MRI-Chromosomal study TORCH screen )If MRI Abnormal consider neurosurgeryIf MRI Normal assess for developmentIf normal development observation mainly familialIf abnormal development consider TORCH Neurodegenrative disorder Autosomal dominant syndromes there will be other associated featuresAetiology and DDx of Microcephaly /Mental retardation/Cerebral palsy1ry1-familial (Autosomal recessive)2-Autosomal dominant (Down,Edward,Cri du chat & Patu syndrome)2ry1-Prenatal causes : Infection TORCH,Irradiation,Toxins as fetal alcohol syndrome2-Natal causes: Hypoxic Ischaemic Injury3-Postnatal: Kernicteurs,Intracranial hemorrhage,C.N.S infection (meningitis & encephalitis)Cri Du Chat Syndromealso 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 features1-microcephaly2-usually round face3-small chin4-eyes are very far apart5-folds of skin over their eyes6-small nose bridge7-feeding problems due to difficulty of swallowing8-severe speech and motor delay (hypotonia)9-hyperactivity and aggressive behaviour

Mental Retardation