Diseases Resulting from Autosomal Chromosome Abnormalities Down syndrome most common chromosomal disorder most common cause of congenital mental retardation causes trisomy 21 nondisjunction (most common cause) occurs during anaphase of meiosis I Robertsonian translocation mosaicism (least common cause) presentation appearance short stature hypotonia unique facial structure epicanthic folds, macroglossia, flat profile, depressed nasal bridge simian crease in palm ↑ risk for congenital heart disease combined ASD and VSD AML (< 3 y/o) ALL (> 3 y/o) Alzheimer's disease by 5th decade due to amyloid precursor protein (APP) gene on 21 Hirschsprung's disease, duodenal atresia, congenital heart anamolies atrioventricular canal is most common endocardial cushion defects also very common screening + quad screen ↓ α-fetoprotein ↓ estriol ↑ inhibin A ↑ β-hCG remember: high (hCG, inhibin); deficit (estriol, fetoprotein) + ultrasound shows high amount of fluid behind the neck ↑ nuchal translucency can confirm diagnosis with amniocentesis or chorionic villus sampling Edwards' syndrome most common trisomy resulting in live birth after Down syndrome cause trisomy 18 nondisjunction presentation mental retardation unique appearance rocker-bottom feet micrognathia small jaw low-set ears clenched hands with overlapping fingers prominent occiput congenital heart disease VSD death < 1 y/o Patau's syndrome cause trisomy 13 nondisjunction presentation mental retardation unique appearance microphthalmia microcephaly cleft lip/palate holoprosencephaly polydactyly VSD cystic kidneys death < 1 y/o Cri-du-chat syndrome cause microdeletion of short arm of chromosome 5 presentation high-pitched crying/mewing origin of name: French for cry-of-the-cat microcephaly moderate to severe mental retardation epicanthal folds VSD Williams syndrome cause microdeletion of long arm of chromosome 7 region lost includes elastin gene presentation distinctive "elfin" facies mental retardation hypercalcemia ↑ sensitivity to Vitamin D unique behaviors well-developed verbal skills extreme friendliness with strangers musical talent supravalvular aortic stenosis 22q11 microdeletions cause microdeletion at chromosome 22q11 abnormal embryological development of 3rd and 4th pharyngeal pouch variable pressenation CATCH-22 disease cleft palate abnormal facies T-cell deficiency due to thymic aplasia cardiac abnormalities hypocalcemia due to parathyroid aplasia results in tetany specific presentation of 22q11 microdeletions DiGeorge syndrome defects in thymus parathyroid heart velocardiofacial syndrome defects in palate face heart no abnormalities thymus, parathyroid