SENSORY

Question 1

PENDRED SYN

Answer 1

Hearing loss (sensorineural HL) + Mondini malformation (Enlarged Vestibular Aqueduct and abnl shaped cochlea) + goiter; HL evident at birth; Genetics: 50% caused by mutations in SLC26A4: Disruption of ion transport; A. Recessive

Question 2

CONNEXIN 26 (AKA GJB2 GENE)

Answer 2

Most common cause of congenital nonsyndromic sensorineural hearing loss

Question 3

CONNEXIN 30 (AKA GJB6 GENE)

Answer 3

DFNA3; “dominant negative” effect

Question 4

USHER SYN

**most common AR syndromic HL

Answer 4

HL + Vision = sensorineural + retinitis pigmentosa (loss of night vision&raquo_space; loss of peripheral vision&raquo_space; tunnel vision); Balance sometimes affected; Types 1 - 3 (1 being most severe); Type 2 does NOT have balance problems; All A. recessive, some w/ digenic inheritance; Type 1 mostly caused by MYO7A; Type 2 mostly caused by USH2A (*AJ founder–50% cases); Type 3 mostly caused by CLRN1 gene

Question 5

WAARDENBURG SYN

**Most common AD syndromic HL

Answer 5

Pigmentary abnl: White forelock, leukoderma (“patchy” skin), heterochromia; dystopia canthorum (appearance of wide nasal bridge due to displacement of inner angle of eye); Sometimes sensorineural HL; Types 1-4: Type 1 classic, Type 2 NO dystopia canthorum, Type 3 type 1 + upper limb defects, Type 4 Hirschsprung’s; High risk for ONTDs&raquo_space; family planning includes folic acid intake for women with Waardenburg; Testing: NGS panel

Question 6

BARDET-BIEDL SYN

Answer 6

Retinal disease with gradual deterioration&raquo_space; legally blind by adolescence/early adulthood; central obesity starting early childhood; Postaxial poly-dactyly; Fetus/infant findings include structural kidney disease, genitourinary malformations, possibly polydactyly; Genetics: A recessive; Many genes all involved in cilia (ciliopathy condition), Most common mutations in BBS1 and BBS10, BBS10–most significant renal impairment; Clinical criteria: Major criteria include retinal dystrophy, obesity, polydactyly, cognitive impairment, renal disease, developmental delays; Testing strategy = NGS panel