Chromosomal Disorders

Question 1

what is the most common chromosome abnormality in live-born babies

Answer 1

trisomy 21

Question 2

what is the most common cause of intellectual disability in the population

Answer 2

trisomy 21

Question 3

common features of trisomy 21

Answer 3

*intellectual disability
*flat facies
*prominent epicanthal folds
*upslanting palpebral fissures
*single palmar crease
*incurved 5th finger
*gap between first 2 toes
*short stature

common complications:
*duodenal atresia
*Hirschsprung disease
*congenital heart disease (AVSD)
*early-onset Alzheimer disease

Question 4

other defects in trisomy 21

Answer 4

AV canal, duodenal atresia, increased risk of megakaryoblastic leukemia (and other leukemias), hypothyroidism, increased incidence of Alzheimers (related to APP gene)

Question 5

mosaicism

Answer 5

*presence of 2 or more populations of cells with different genotypes in one individual
1. somatic mosaicism: mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs
2. germline (gonadal) mosaicism: mutation only in egg or sperm cells; if parents and relatives do not have the disease, suspect gonadal (or germline) mosaicism

Question 6

trisomy 13 (patau syndrome)

Answer 6

*low life expectancy (death usually by age 1)
*findings:
-cutis aplasia (scalp defect)
-microphthalmia (small eyes)
-microcephaly
-polydactyly
-holoprosencephaly
-severe intellectual disability

Question 7

trisomy 18 (edwards syndrome)

Answer 7

*clinical features:
-prominent occiput
-rocker bottom feet
-intellectual disability
-nondisjunction
-clenched fists with overlapping fingers
-low set ears

Question 8

Turner syndrome (45, XO)

Answer 8

*single copy of X chromosome, exclusive to FEMALES
*at increased risk for X-linked recessive disorders
*clinical features: short stature, ovarian dysgenesis (streak ovary), broad chest with widely spaced nipples, high arched palate, webbed neck
*complications:
-heart: bicuspid aortic valve, coarctation of aorta
-renal: horseshoe kidney
-repro: primary amenorrhea, infertility

Question 9

Klinefelter syndrome (47, XXY)

Answer 9

*extra X chromosome in MALES
*leading cause of male infertility
*clinical features: small, firm testes; tall stature; reduced secondary sex characteristics; gynecomastia

Question 10

22q11.2 deletion syndrome

Answer 10

aka DiGeorge Syndrome
CATCH 22:
Cardiac abnormality
Abnormal facies
Thymic hypoplasia/aplasia
Cleft palate
HYPOcalcemia
*Tetralogy of Fallot
*increased risk of schizophrenia
*immune deficiency

Question 11

Williams syndrome

Answer 11

*congenital microdeletion on 7q11.23
*clinical features:
-distinctive “elfin” facies (periorbital fullness, wide mouth, widely spaced teeth, large ear lobes)
-cocktail party personality: well-developed verbal skills, extreme friendliness with strangers
-HYPERcalcemia
-stellate irides
-supravalvular aortic stenosis

Question 12

cri-du-chat syndrome

Answer 12

*congenital deletion of short arm of chromosome 5 (5p minus)
*clinical features:
-differences in structure of larynx associated with UNUSUAL, HIGH-PITCHED CRY (cri-du-chat = cry of the cat)
-hypertelorism
-microcephaly
-downturned mouth
-behavioral issues (aggressiveness, etc)
-cardiac abnormalities (VSD)

Question 13

Prader-Willi syndrome - clinical presentation

Answer 13

*hyperphagia: ABNORMAL FOOD-SEEKING BEHAVIORS or insatiable appetite
*obesity
*almond shaped eyes
*intellectual disability
*hypogonadism
*hypotonia

Question 14

Angelman syndrome - clinical presentation

Answer 14

*“Happy Puppet = always laughing and smiling, ATAXIA, seizures, no speech
*hand-flapping, ataxia, severe intellectual disability, inappropriate laughter, seizures

Question 15

genetics of Prader-Willi syndrome

Answer 15

Paternal deletion (on 15q11-q13)

Question 16

genetics of angelMan syndrome

Answer 16

Maternal deletion (on 15q11-q13)