Congenital / Chromosomes

• MR - IQ 35-70
• general hypotonia (CNS origin; meet most major milestones at 2x normal age)
• balding scalp hair pattern
• upslanted eyes w/epicanthal folds
• extra neck skin folds
• flat nasal bridge, prominent tongue
• joint laxity
• brushfield's spots on irises
• subendocardial cushion defect (ASD/VSD, AV canal)
• duodenal atresia, Hirschsprung's, imperforate anus
• hypothyroid (screen yearly)
• early onset dementia
• increased risk leukemia
• atlantoaxial instability

triple helix of collagen VI - abnormal in Downs; imp in scaffolding during embryologic development of nervous & connective tissue

• low set ears, small mouth, short sternum
• thumb & radius agenesis/hypoplasia
• camptodactyly (little finger fixed in flexion)
• redundant cardiac valve leaflets
• hypertonia
• seizures
• rocker bottom feet
• **only 5-10% survive beyond 1st yr

• holoprosencephaly (fail telencephalon to divide to 2 hemispheres; central lg ventricle)
• microphtalmia + other eye defects
• midline facial cleft
• polydactyly
• scalp cutis aplasia
• cystic kidneys
• VSD
• **5% survive past 6 mos

45, XO

• short stature
• phenotypically female
• perygium colli (webbed neck)
• smll mandible, narrow maxilla, high arch palate
• epicanthal folds
• increased distance btw nipples
• pedal edema
• cubitus valgus
• impaired hearing (sensorineural)
• delayed motor skill development w/ normal intelligence
• coarctation of aorta + bicuspid aortic valve
• ovarian dysgenesis

• extra X chromosome in males
• 47, XXY most common
• 48, XXXY or more also seen

(1/500 males; advanced maternal age is risk factor)

• hypogonadism
• azoospermia
• tall
• female hair distribution
• learning disabilities
• delayed motor skill development
• Barr body present (inactivated x chrom)

• admin testosterone during puberty to improve secondary sex characteristics
• developmental delay/learning disabilities interventions

• 75% maternal deletion 15q11 -> q13
• 23% chrom 15 mutations

• happy, laughing disposition ('happy puppet')
• attractive, lighter pigmentation than family
• MR (severe)
• microcephaly
• ataxia
• hypotonia
• epilepsy (80%) w/ EEG findings
• absent speech
• lg. mandible, open-mouthed expression revealing tongue

• supportive
• seizures often refractory to anticonvulsant therapy
• normal life span

• 75% paternal deletion 15q11--> q13
• 25% maternal disomy

hyperphagia/lack of satiety, decreased caloric requirement 2/2 to hypotonia/decreased movement, & obsessions/compulsions that focux on food --> vicious cycle

• hypotonia & poor feeding in infants --> hyperphagia/obesity
• precocious puberty
• micropenis
• mild MR
• sleep disturbances
• lighter pigmentation than family
• sig behavior probs (stubborn, manipulate, aggressive)
• fluent speech
• obsess/compulsive traits

• growth hormone to promote stature; other hormone supplementation to promote secondary sex characteristics
• obesity complications limit life span

• normal/ low-norm intelligence
• phenotypically normal
• tall, severe acne
• rarely, antisocial behavior

• 47, XXX
• phenotypically normal female w/ norm sex development & menarche
• variable severity of speech/language delays, lack coordination, & poor academic performance
• may be gangly, tall, & have behavior disorders

• MR, worse w/ increasing # X's
• epicanthal folds, hypertelorism, clinodactyly, CHD, radioulnar synostosis
• often incomplete sex maturation
• often tall w/XXXX, short w/ XXXXX

• 46, XX
• 46, XY
• chrom 12

• similar to Turner's
• facies: traingular, hypertelorism, down-slanting eyes, ptosis, strabismus, amblyopia, low set ears w/ thick helices, high nasal bridge, short, webbed neck
• pectus carinatum/excavatum, scoliosis
• cardiac: pulm stenosis, ASD, or hypertropic cardiomyopathy
• assorted skeletal abnormalities
• skin: lymphedema, prominent pads of digits
• neuro: hypotonia
• MR in 25%
• delayed sex maturation, premature ovarian failure; >1/2 males have undescended testes

• Etiol: x-linked dominant, triplet repeats
• Epidem: 1/2,000 births; M=F
• Risk: family hx

• MR
• macroorchidism in boys
• protruding ears
• triangular, elongated facies
• flat malar bones
• shyness, autistic behavior, avoidance of eye contact

• rare, x-linked recessive disorder of basement membranes of kidney, eye, & ear (type IV collagen)
• glomerulonephritis, ESRD by age 40 (men)
• hearing loss (90% of males)

Think: Alport's syndrome

ppl in every generation affected

• skips generations (often parents w/ similar condition)
• hx early deaths from unknown d/o's or multiple miscarriages
• consanguinity increases odds

• only males affected
• females unaffected or only partially affected (due to lyonization) carriers of the trait

• surgical repair of lip w/i first mos of life
• palate ~1 yr of life
• potential for final repairs & scar revisions in adolescence

• clefting of lip & anterior (primary) palate due to defect in fusing of both maxillary processes w/frontonasal process during weeks 5-6
• clefting of posterior (secondary) palate due to defect in fusion of palatal shelves during weeks 7 & 8

• herniation of abdominal contents (usually only intestine) through umbilical root, covered only by peritoneum
• Tx - serial reductions of intestines back into abdomen until skin closure possible

• AFI < 5.0 cm
• Complications: fetal demise; pulmonary hypoplasia; facial deformities; skeletal deformities (compressed thorax, twisted feet)

• bilateral renal agenesis
• includes: pulmonary hypoplasia, skeletal anomalies, & characteristic facies (sloping forehad, flat nose, recessed chin, lowset, floppy ears)
• incompatible w/ neonatal life