Ch 6 - Disorders of Autosomes and Sex Chromosomes

Trisomy 21

down syndrome

• 1/700

• hypotonia, short stature, loose skin on nape, singular palmar crease, clinodactyly

• flat ociput, epicanthal folds, upslanting palpebral fissures

• moderate to mild intellectual disability

• congenital heart disease, duodenal atresia, risk for leukemia, risk for premature dementia

• 60 yr life expectancy

Trisomy 18

• 1/7,000

• hypertonia, prenatal growth deficiency, characteristic fist clench, rocker-bottom feet

• receding jaw, low-set ears

• severe intellectual disability

• severe heart malformations, feeding difficulties

• life expectancy less than 1 yr

Trisomy 13

• 1/10,000

• microcephaly, sloping forehead, characteristic fist clench, rocker-bottom feet, polydactyly

• ocular abnormalities, cleft lip + palate

• severe intellectual disability

• severe CNS malformations, congenital heart disease

• 50% die in first month, 90% die in first year

Maternal age and down syndrome

if mom over 30, risk changes from 1/700 to 1/10

Paternal age and down syndrome

if occuring due to paternal NDJ, 10% of cases in meiosis 2

mosaic down syndrome

milder phenotype, 2% of patients

primary down syndrome

47 chromosomes, one extra chromosome 21

• 95% of cases

familial (translocation) down syndrome

robertsonian translocation of 21q and long arm of 14 or 22

• 46 chromosomes but trisomic or genes in 21q

• parental carrier has 45 chromosomes

21q21q translocation down syndrome

2 chromosome 21 long arms, 46 chromosomes total

• originate as isochromosome

partial trisomy down syndrome

rarest, only part of 21q present in triplicate (2.5 chromosome 21)

• arises from NDJ and delection

uniparental disomy

the presence of a disomic cell line containign two chromosomes

• can be clinically benign

• can cause an autosomal recessive disorder if only one parent is a carrier

• can cause phenotypic changes if the chromosome has a high degree of imprinting

isodisomy

two chromosomes derived from identical sister chromatids

heterodisomy

both homologs form one parent are present