SYNDROME
GENETICS
FEATURES
CLUE · LABS
22q11.2 deletion
DiGeorge · velocardiofacial
Microdeletion → 3rd/4th pharyngeal pouch maldevelopment
Cleft palate, abnormal face, thymic aplasia, conotruncal heart defects, hypocalcemia (tetany)
FISH or microarray · psychiatric illness later
Williams syndrome
7q11.23 (incl. elastin)
Microdeletion
Elfin face, extremely friendly, verbal strengths, ID, supravalvular aortic stenosis, renal artery stenosis
Hypercalcemia (↑ vitamin D sensitivity)
Terminal deletion
High-pitched cat-like cry, microcephaly, severe ID, epicanthal folds, VSD
"Cry of the cat = chromosome 5"
Most often paternal nondisjunction or loss; mosaicism common
Short stature, webbed neck, shield chest, lymphedema of hands/feet, streak ovaries (primary amenorrhea), bicuspid aortic valve, coarctation, horseshoe kidney
↑ FSH/LH, ↓ estrogen · GH and estrogen therapy · Y material → gonadoblastoma
Klinefelter syndrome
47,XXY
Nondisjunction (either parent)
Tall, eunuchoid proportions, small firm testes, infertility, gynecomastia, female hair pattern, mild learning issues
↓ Testosterone, ↑ FSH (Sertoli/inhibin ↓), ↑ LH · Barr body present
Paternal meiosis II nondisjunction
Tall, severe acne, normal fertility, learning/behavioral issues
Usually undiagnosed
Nondisjunction
Tall, often normal; some learning delay, early menopause
Two Barr bodies
Androgen insensitivity
46,XY · AR gene
Testes make testosterone, but receptors don't respond
Female external genitalia, blind vagina, no uterus, undescended testes, breasts present
↑ Testosterone, ↑ LH · remove testes after puberty
5α-Reductase deficiency
46,XY · AR
Can't make DHT
Ambiguous genitalia at birth, virilize at puberty
Normal testosterone and LH, ↓ DHT
GnRH neurons fail to migrate (KAL1 and others)
Delayed puberty + anosmia
↓ GnRH, FSH, LH, sex steroids
Too small for karyotype
FISH (targeted) or chromosomal microarray
See 4.02