5 Endocardial cushion defect Special Olympics: Atlantoaxial instability Down Syndrome/Trisomy 21Full trisomy %Mosaic trisomy %Translocation %TranslocationsParent carrier t(21q;21q) % recurrenceParent carrier t(14q;21q) 1/3 chance of having affected childIF THE PATIENT HAS A TRANSLOCATION THE PARENTS KARYOTYPE SHOULD BE CHECKEDHeart defect:Endocardial cushion defectSpecial Olympics:Atlantoaxial instability
6 Risk Table for Down Syndrome Maternal AgePrevalence at Live Birth251/1350301/890351/355401/97451/23Note from Caroline: You need to know these numbers cold!Note from Rachel: I’d rather memorize developmental milestones or stick a fork in my eye!
7 CRANIOSYNOSTOSIS Simple 1 fused suture Complex > 1 suture premature fusion of 1 or more cranial sutures,often resulting in an abnormal head shapeSimple fused sutureComplex > 1 sutureSyndromic Complex+other malformationsShould be recognized before 5 mo of age
8 What cutaneous finding is associated with Crouzon syndrome? The craniofacial syndrome associated with cervical spine fusion, OM, and syndactyly.Aperts71% of patients with this CFS have Chiari I type malformations and hydrocephalusCrouzonWhat cutaneous finding is associated with Crouzon syndrome?Acanthosis nigricansWhich CFS is associated with medially deviated great toes & broad radial thumbs?Pfeiffer Syndrome
13 You see a baby in the NICU with feet like this… What lab test would confirm the diagnosis?Chromosomes (45, XO)
14 Most common cardiac defect in TS Coarctation of the aorta. Turner Syndrome / 45,X0Short stature, webbed neck, delayed secondary sexual characteristics, short 4th-5th metacarpals, widely space nipples, pedal edema, cubitus valgusMost common cardiac defect in TS Coarctation of the aorta.It is the most common chromosomal defect in spontaneous abortions
16 Holt-Oram SyndromeInheritanceAutosomal DominantDiagnostic criteria:Abnormalities of the thumbtriphalangiahypoplasiaaplasiaCongenital heart disease.atrial septal defectsarrhythmia
17 What diagnosis should you suspect? A 4 year old boy presents because he’s been falling a lot per his parents. His dad is mad because the child “walks like a girl on his tippy toes.”What diagnosis should you suspect?Duchenne’s Muscular DystrophyCan someone demonstrate a physical exam finding seen in this disease?Gower signWhat would be the diagnostic finding on muscle biopsy?Absence of dystrophin
18 Duchenne Muscular dystrophy is the most common hereditary muscular disease,a X linked recessive disorder inheritedby more than 1:4000 boys.Pseudohypertrophy of the calvesGower sign
19 Patient started having difficulties in school when he was eight years old. His teacher noted that he seemed to be irritable and impulsive; she raised the possibility of attention deficit disorder. In addition, Ronnie was noted to have mild difficulties with spelling and composition. Although he was requiring some additional help with these tasks, his IQ was normal (104) and he had been progressing academically with his peer group. He was tall for his age (95th percentile in height). He had no physical or medical problems. A detailed evaluation by a psychologist revealed some impulsivity, but insufficient findings to support a diagnosis of attention deficit disorder. Tutoring was arranged, and he continued to progress adequately in school. At age 14 years, he develops gynecomastia. At this point, he is seen by an endocrinologist.What is the diagnosis ?Klinefelter SyndromeTreatment: TESTOSTERONE
20 You also need to know Normal testicular volume Age, yr Length, cm (mean ± SD)Volume, mL (approximate)< 21.4 ± 0.42 - 41.2 ± 0.24 - 61.5 ± 0.616 - 81.8 ± 0.38 - 102.0 ± 0.522.7 ± 0.753.4 ± 0.8104.1 ± 1.0205.0 ± 0.5295.0 ± 0.3
21 Café au Lait spot with irregular borders like the coast of Maine McCune Albright SyndromeCafé au Lait spot with irregular borders like the coast of MainePrecocious PubertyAppearance of physical and hormonal signs of pubertal development at an earlier age than is considered normalMales <9 yearsFemales < 8 yearspolyostotic fibrous dysplasia :abnormal fibrous tissue growth in many bones. Normal bone is replaced by irregular masses of fibroblast cells.
22 Cri du Chat/ Deletion 5pOne of the most common human deletion syndromes with an incidence 1 in 20,000 to 1 in 50,000 birthsThe syndrome was discovered in France in 1963 by a team headed by the late Jerome Lejeune.The peculiar cry of affected infants sounded to Lejeune like the meowing of a Parisian cat.The syndrome involves severe developmental and mental retardation and a characteristic constellation of congenital malformations:microcephalyround facehypertelorismmicrognathiaepicanthal foldslow-set earshypotoniamotor and mental retardationAlthough the majority of patients die in early childhood, some survive into adulthood and exhibit an IQ below 20.
23 This girl has hearing problems but otherwise does well in school. What is her diagnosis?Treacher CollinsWhat might clue you in on family history?Multiple family members with hearing aids
24 Noonan SyndromeAKA as Male Turner, but don’t be fooled it can be present in females due to AD inheritance.Clinical FeaturesShort statureCongenital heart defect (Pulmonary Stenosis)Webbed neckSuperior pectus carinatum, inferior pectus excavatum,Apparently low-set nipples;Developmental delay of variable degree;Cryptorchidism;Characteristic facies:low-set, posteriorly rotated ears;vivid blue or blue-green irises;wide-spaced eyes with epicanthal foldsthick or droopy eyelids.Coagulation defects3 genes associated:PTPN11, KRAS, SOS1
25 What other complications is he at risk for? You have an obese 6 year old male who was brought in because his mom is frustrated that he is always waking up and stealing food from the kitchen at night even though he’s on a diet.What is the mechanism of action for the diabetes he will likely develop?It’s type 2 DM due to insulin resistanceWhat other complications is he at risk for?GH deficiency, hypogonadism, osteoporosis, hypothyroidism, SCFE, sleep apnea….
26 Hypotonia, Obesity, small hands and feet Prader-Willi SyndromeHypotonia, Obesity, small hands and feetEtiologyDeletion 15q11-q % casesMaternal UPD % casesImprinting mutation % cases
27 Profound speech impairment Ataxia and other movement disorders Angelman SyndromeClinical FeaturesSevere DDMProfound speech impairmentAtaxia and other movement disordersInappropriate laughterShort attention spanMicrocephaly and seizuresWide spaced teethHypopigmentationRemember IMPRINTING2 alleles from MOM PWS2 alleles from DAD AS
28 Beckwith Wiedemann Syndrome Clinical FeaturesMacroglossiaOmphaloceleMacrosomiaHypoglycemiaHemihypertrophyHypospadiasIndentation on posterior helix
29 DiGeorge Syndrome/ Deletion 22q11.2/VCF Inheritanceautosomal dominantClinical Featuresaplasia or hypoplasia of the thymus (immunodeficiency)aplasia, or hypoplasia of the parathyroid glands (Hypocalcemia)conotruncal cardiac defectsHearing loss, CL/CP, velopharyngeal incompetence, prominent nose, narrow alae nasi, long faceSlender fingersWhat lab test makes the diagnosis:FISH 22qVSD (62%) R AoArch (52%), TOF (21%)
30 You would use FISH to detect all of the following syndromes except: Prader williEdwardsVelocardiofacialWilliamsCri du chatAll of them are deletions except Edwards (check chromosomes)
31 Supravalvular Ao stenosis Williams SyndromeMental retardation, dysmorphic facies, infantile hypercalcemia, growth deficiency, cocktail personality, hoarse voice, enamel hypoplasiaSupravalvular Ao stenosis
32 Mild to moderate microcephaly Short palpebral fissuresEpicanthal foldsShort nosemid face hypoplasiaThin/smooth upper lipLong philtrumPrenatal and postnatal growth delayNeurodevelopmental deficitsFetal Alcohol Syndrome