+ Clinical features Vepecomats, | Y Tall stature v Small testes v Micropenis Y Normal pubic and axillary hair ¥ Intellectual disability ¥ Infertility ¥ Behavioral problems The most common cause of primary hypogonadism and infertility i males ‘% Mode of inheritance? ¥ Autosomal dominant ¥ PTPN11 gene on 12424 Laboratory finding ? ¥ Low testosterone Y High FSH/LH Increases risk of : ¥ Pulmonary disease ¥ Varicose vain ¥ ADHD. @ increases risk of which Malignancies ? Y Breast cancer Y Testicular cancer % What is the most effect treatment ? ¥ Testosterone replacement therapy __Woonsavares “What is the most common cardiac defect? Increases risk of which Malignancy ? haute ymshootic leukemia (ALL) 7 Chronic myeloid leukemia (CML)Clinical features v Long narrow face Y Prominent jaw Y Big ears ¥ Large hand and feet ¥ Macroorchidism v Hyperextensible joints Y Intellectual disability ¥ Behavioral problems (Autism, ADHD) Y Speech delay ¥ Pes planus (Flat foot) Woonsquares Mode of inheritance? X-linked dominant inheritance > 200 CGG repeats in FMRI gene * Clinical features ¥ Short stature ¥ lymphedema of hands & feet Y Shield chest Y Cubitus valgus ¥ Low posterior hairline ¥ Posterior rotated ears ¥ Webbed neck ¥ Short 4** metacarpal bone ¥_Normal intelligence (except Math) ‘ What is the most common cardiac defect? 1. Bicuspid aortic valve wi defect: ¥ Mitral valve prolapse The most common form of inherited intellectual disability But The 2" most common genetic intellectual disability (after trisomy 21) ‘ How to confirm the diagnosis ? ¥ Molecular genetic test for CGG allele repeat size F Cana female have fragile Xsyndrome? ¥ Yes, but milder symptoms ‘Labs finding ? High FSH ‘High FSH/LH ¥ Lowestradiol Wha anomaly ? Y Horseshoe kidney ¥_ Double collecting system ‘% Increases risk of: Y Hypothyroidism Y Hashimoto disease Y Celiac disease Inflammatory bowel disease Increases risk of which Malignancy? Y Gonadoblastoma ‘% Treatment Y Growth hormone Y Estrogen therapy% Clinical features Y Midline defect ¥ Aplasia cutis congenita ¥ Microphthalmia 1 ¥ Microcephaly 2 Y Postaxial polydactyly Y Hypotonia ¥ Holoprosencephaly ¥ Hypoplastic / absent ribs Y Abdominal wall defect 34 most common autosomal trisomy “ Most common cardiac defect ? Ventricular septal defect (VSD) Atrial septal defect (ASD) 3. PDA ‘“ Most common cause of death? Y Central apnea 7° ¥ Deafness ¥ Colobomas * Prognosis ¥ 70% die in the 1* 3 months of Y Capillary hemangioma life Y Genital anomalies ¥ Clenched fist ‘ Clinical features ¥ Long philtrum (Elfin face) ¥ Broad mouth. Y Short nose with bulbous nasal tip. Y Cocktail personality ¥ Mental retardation ¥ Joint laxity Voonsquares| ¥ 95% die by 3 years of age ¥ Rarely reach up to 10 years % Mode of inheritance? ¥ Autosomal dominant ¥ Microdeletion 7q % Laboratory finding ? ¥ Hypercalcemia “% Most common cardiac defect ? Y Supravalvular aortic stenosis (80%) Y Peripheral pulmonic stenosis ¥ Pulmonary valvular stenosis Eye problems ? Y Stellate irises Y StrabismusMode of inheritance? ¥ Denovo mut ¥ 5p deletion Clinical features Y High pitched (Cat's like) cry (arynx anatomical changes) Y Moon face with wide spaced eyes v Wide and flat nasal bridge v Hypotonia ¥ Down slanting palpebral fissures Y Microcephaly v Feeding difficulties ¥ Intellectual disabilities ¥ Failure to thrive Voonsquares “Common cardiac defect ? ‘Ophthalmology ina fetures Myonia Cataract Glavcoma Brushed spots (speckled iss) Nystagmus Srbiemus Lc | & ¥ VSD, ASD, PDA & TOF = Rewropeyhiatric nding ¥ Hypotonia Developmental tay Duodenal atresia Annular pancreas Tchessophape le Hischsprungdsease % mpertoated anus Facial nial featurer Y sracreepraly % Upslones palpebral fissures % fpiantnal fice % Three fotanels taerocepnaly % Neonatal cholestasis short eck, redundant skin Short metacarpals and phalanges Short 5 gt with nodactyy Single wansverse palmer creases Wie gap between 1" & tes Short sternum rey Mipdyptsia Recurent jolts socation Musculoskeletal cial festures ‘lantoaua neta fxmen enc) % towset ears 1 Celiac disease (erent 2¥0) % Hearing oss Narcan 2 Nose in ‘Cardiac clea nding: What is the cause of polyuria and polydipsia? y . oie Nephrogenic diabetes insipidusClinical features ¥ Macrodactyly ¥ Hemihypertrophy ¥ Skin changes (lipomas, vascular malformations, connective tissue nevi, epidermal) Scoliosis Tissue hypertrophy Accelerated growth Developmental delay Increase risk of malignancies ‘> Mode of inheritance? ‘+ Increases risk of which Y Sporadic Malignancies ? v jet Weonseeare | | Embvyenietinon Clinical features “ Mode of inheritance? ¥ Zygomatic and mandibular bone hypoplasia ¥ Autosomal dominant v Eyelid colobomas v TCOF1 gene Y Sparse eye lashes Y Microretrognathia Y Choanal atresia Y Microtia Y Conductive hearing loss Y Cleft lip / palate ‘© Clinic follow up ? ¥ Vision assessment v Hearing assessment ¥ Feeding difficulties Y Speech therapy ¥_Psychosocial therap + Most common neonatal problem? Airway difficulties “+ What is the level of intelligence ? v NormalClinical features Short stature below 3rd percentile Rhizomelic Shorting (Short proximal long bones) Trident hands Stenosis of foramen magnum. Macrocephay, IMiaface hypoplasia lce cream scoop shape femoral head Saured-off lac wings (Champagne ess sign). Sane Increase risk of OSA & UAO. ¥ Autosomal Dominant Delay in gross mator development. _Weonsaunres ¥ Defect in FGFR-3 Clinic follow up ? Y Head circumference. Y Hearing test annually.| | * Spinal Xray specific finding ? ¥ Polysomnography. Y Narrowed interpeduncular distances Mode of inheritance? acs features ¥ ‘Autosomal dominant ¥ Generalized joint ¥ Rarely AR hypermobility Hyperextensible skin : “F Most common cardiac Fragile skin : : defect? Increased bruising lid leben oteaien) ¥_ Aortic rot itatation Velvety skin kyphoscoliosis Laboratory finding Swan-neck malformation Include normal Piezogenic papules beanie an ¥ Capilacy fragiy test on Capi fragt test Cigarette paper scar ‘Monitoring? Fish mouth appearance ¥ Annual of skin tears. ( echocardiogram. Hypotonia ‘& Most severe type? pense scular (vEDS; EDS feonsquares type IV)-— - 2) Thanatophoric Dysplasia ical features Rhizomelic Shorting ‘Small chest ee Absent sciatic notch. French-telephone femurs. H-shaped vertebrae. Cloverleaf skull (severe craniosynostosis). Types + Type! "Without cloverleaf skull * Telephone receiver femur + Typell = With cloverleaf skull + Straight femur Weorsauares Platyspondyly (flattened vertebral bodies). “% Most common cause of death? ¥ Craniocervical junction ‘compression ¥ Pulmonary hypoplasia 2) Infantile cortical hyperostosis (Caffey Disease) Clinical features Extreme irritability. Soft tissue swelling. Fever. Anorexia. Cortical thickening of bones. Pseudoparalysis Differential diagnosis a + Osteomyelitis + Hypervitaminosis A, & + Child abuse. + Leukemia VW sonsai ‘The bone changes typically + Most common affected bone? begin before six months of age yy i {and resolve by two years. paeocene * Mode of inheritance? Y Autosomal dominant ¥ COLIA1 gene % Laboratory finding ? ¥ Leukocytosis ¥ Thrombocytosis Y High ESR High Alkaline phosphatase + Prognosis Y Self-limited condition Y Deformities of the involved bones.Clinical features + Short stature Scoliosis Blue sclera Woorsas Dentinogenesis imperfecta Hyperextensible joints Easy bruising Wormian bones (small, regular bones along the cranial sutures) Codfish vertebrae Flared metaphysis (popcorn-like) o Mode of inheritance? ¥ AD (I-IV) Y AR (rare types + IIB) ¥ COLIA1 gene Clinical features “ Mode of inheritance? Y Autosomal dominant v FBN1 gene Major criteria: ¥ Ectopia lentis. ¥ Aortic dilatation or dissection. ¥ Family history Systematic score features 2 major criteria +L major + FBN1 gene mutation +L major +37 more systematic score “+ Common Types 1. Type! "Most common = Mildest form * Classic nondeforming + Hearing loss in 50% Type ll = Most severe * Death during newborn Type Ill = Progressive deforming "Hydrocephalus Type IV * Normal sclera "Tibial bowing (hallmark) “ Laboratory finding ? ¥ High alkaline phosphatase Y Hypercalciuria ‘ Monitoring? ¥ Annual echocardiogram. o Woonsquares How to confirm the diagnosis? Ghent criteria ‘ Most common cardiac defect ? Y Mitral valve prolapse Aortic root dilatation “% Most common cause of death? ¥ Cardiovascular complications ¥ Rupture aortic root dilatation32) Apert syndrome Other Craniosynostosis syndromes ‘Clinical features ‘ Craniosynostosis syndromes Y Complex syndactyly (mitten hana) Apert syndrome (sicoronal suture) ¥ Bicoronal craniosynostosis pore eee ¥ Maxillary hypoplasia Carpenter syndrome (Multinie sutures) 7 Saethre-Chotzen syndrome (Miuitipl sutures) i. Si Far) Pfeiffer syndrome (Muitpl sutures) ¥ Hypertelorism v Midface hypoplasi eo ‘+ Mode of inheritance? ¥ Intellectual disability All ofthem Autosomal dominant except — Y Carpenter syndrome (Autosomal recessive) ‘What isthe most common dermatological Koen pleat ntl pest sya “Which craniosynostosis syndromes have normal intelligence? ¥ Severe acne vulgaris, ¥ Crouzon syndrome ‘Which ranlosynostoss syndromes have normal hands? ¥ Crouzon syndrome (wo syndacty¥) “Which craniosynostosis syndromes without hypertelorism? ¥ Saethre-Chotzen syndrome Wo nsaus 28) Branchio-oto-renal (BOR) syndrome Clinical features ¥ Branchial cleft fistulas / cysts ¥ Preauricular pits / tags % Laboratory finding ? ¥ Renal aplasia / hypoplasia ¥ Lowrenin Y Sensory / conductive hearing loss Low aldosterone g 4 ¥ Hyperkalemia ¥ Pulmonary hypoplasia eo eae ee y ‘Major crten Metabolic acidosis27) Goldenhar syndrome (oculo-auriculo-vertebral spectrum) Clinical features ¥ Facial asymmetry (hemifacial macrosomia) Y Microtia ¥ Preauriculartags Y Microphthalmia Y Limbal (Epibulbar) dermoid (Pathagnomic) ¥ Eyelid coloboma ¥ Facial nerve involvement leads to hypoplasia of the facial muscles. ¥ Hypoplasia or absence of the parotid gland. ¥ Vetebral anomalies (Hemivertebrae) Y Cardiac defect (VSD) “ Mode of inheritance? Y Sporadic ¥ Abnormal 1% and 2"! brachial arches ws 35) Osler Weber Rendu Syndrome (Hereditary hemorrhagic Telangiectasia) ‘Conjunctival finding in Hereditary hemorrhagic Y Telangiectasia lips, gingiva, tongue, palate Telangiectasia (HHT) and palpebral conjunctiva) Y Recurrent epistaxis (Night time) vs ¥_ Vascular malformation (Lung, liver, Gl & brain) |] ataxia Telangiectasia (AT) “ Complications ? Intracranial hemorrhage Y Pulmonary hemorrhage Y Glbleeding30) Stickler syndrome (hereditary arthroophthalmopathy) Ka =," Clinical features % Mode of inheritance? Y Pierre Robin sequence + ¥ Autosomal dominant ¥ Flat midface and nasal bridge ¥ Joint hypermobility ¥ Myopia + What is the pathognomonic eye finding? Y Vitreous gel anomaly ¥ Sensorineural deafness *? What is ophthalmic emergency associated ¥ Cleft of the soft palate with stickler syndrome? Y Arthritis ; 5 ¥ Retinal detachment Clinical features Y Cerebellar ataxia ¥ Oculocutaneous telangiectasia * Bulbar conjunctivae = Ears = Neck * Cubital fossae ¥ Recurrent infection ¥ Increase risk of malignancy + Mode of inheritance? Y Autosomal recessive ¥ ATM gene ¥ Due to chromosome instability ‘> Laboratory finding ? v High serum alpha- fetoprotein (AFP) ¥ High carcinoembryonic antigen (CEA) Y Low iA eG & let ‘% What is the most consistent laboratory abnormality? ¥ High AFP ‘+ Which part of immune system paired? Both cellular and humoral immunity * Associated with increase sensitivity to ionizing radiation _W eo»sausresa Mode of “Clinical features oe inheritance? Y Long eyelashes ane Y Bushy and arched eyebrows |} dominant Y Hirsutism Y Low hairline petetedieaas ¥ Downward-turned mouth Pulnonary stenosis v IUGR vs ASD Y Short stature Coa, Y Thin upper lip Y Micromelia Y Lobster hand Y Syndactyly Y Ulnar dysplasia ¥_ Mental retardation Weonsai ¥ Mandibular hypoplasia Y Micrognathia Y Glossoptosis (uaciwarsaspicement ofthe tongue) Y U shaped cleft palate Y Birdlike facial appearance. eo ¥ Upper airway obstruction ‘ Mode of inheritance? Wo0nsaues ¥ De novo mutation ¥ SOX9 gene “Most common cause of death? ¥ Upper airway obstruction’ 36) Bloom syndrome + Clinical features & increase Ok ct Y Café-au-lait spots Malignancies ¥ Photosensitive rash ¥ Immunodeficiency ¥ Long narrow face — ¥ Prominent nose ‘Laboratory finding ? v IUGR ¥ Low immunoglobulin level Y Microcephaly ¥ lymphopenia Y Short stature [eonsquares ¥ Infertility % Most common cause of death? v Immune deficiency aCe ‘+ Mode of inheritance? = Mainly leukemia Y Autosomal recessive Y Due to chromosome Avoid radiographs instability ‘Adequate sun protection Clinical features Se Pre ¥ White forelock a eS v Square face Wormel ¥ Thin nose, wide nasal bridge | | @qy—> aye ¥ Dystopia canthorum e v Heterochromia ¥ Sensorineural deafness ¥ Skin depigmentation Hypertelorism + Most common gastrointestinal association? & ¥ Hirschsprung disease Waonsquares3a) Neurofibromatosis type 2 (MISME syndrome) % Diagnostic criteria (1 of the following sets) ¥ Bilateral vestibular schwannomas (acoustic neuromas) ¥ Unilateral vestibular schwannoma AND fist-degree relative with NF2 Y Unilateral vestibular schwannoma Or first-degree relative with NF2 AND any 2 of the following + Meningioma Nonvestibular schwannoma ner clinical features Ependymoma Hearing oss Cans Tits % What is * manifestation typically appears? || Mode of inheritance? Y Autosomal dominant Cataract v _ NF2 gene on chromosome * What is most common type of tumor in NF2? = ¥ Schwannomas Weviieuass Café-au-lait macules can be seen but are much less frequent in NF2. INF2 isnot associated with the cognitive impairment that is often seen with NFL “& What is most common affected cranial nerve with schwannomas? ¥ CN VIII (vestibulocochlear nerve) Diagnostic criteria (>of the following) |] * Mode of inheritance? ¥ 26 café-aurlait macules ¥ AD (50%) ‘+ >5:mmin in prepubertal ¥ Denovo (50%) + >15 mm inin postpubertal v NFL gene on > 2 neurofibromas or 1 plexiform neurofibroma aiamiecen it Axilary or inguinal freckling (Crowe sign) Optic glioma: 2 rls hamartoma (Lisch nodules) Distinctive bony lesion: ¥ Malignancies + Sphenoid dysplasia, or ¥ Primary HTN + Tibial pseudoarthrosis, or ¥ Learning disabilities + Cortical thickening of the long bone ¥ Seizures ¥_Afirst-degree relative with NFL * Increases risk of : % Follow up: ¥ Annual vision exam ¥ BP monitoring @ What is most common type of benign tumorin ¥ Annual full physical NFL? ‘examination ¥_Neurofibromas Woonsa ¥_Tumor surveillance