Hereditary Hearing Impairment

Question 1

Classification of HHI

Answer 1

Syndromic (15-30%) vs Nonsyndromic (70%)

Question 2

Nonsyndromic HHI classification

Answer 2

By mode of inheritance

• Auto Rec (DFNB): 80%
• Auto Dom (DFNA): 20%
• X-linked (DFN)
• Mitochondrial

Question 3

MCC of recessive deafness

Answer 3

GJB2 (Gap Jxn Beta 2) gene encoding for connexin 26

Specifically, c.35delG

Question 4

Pendred syndrome

Answer 4

MCC syndromic hearing loss (10%)
SNHL (congenital, b/l, mod-profound, sloping in higher freq, progressive)
Goiter (usu before puberty)

50% euthyroid, 50% hypothyroid
Enlarged vestibular aqueduct
Mondini-type malformations have been assoc
+/- depressed vestibular fnc

Gene: PDS/SLC26A4 - anion exchanger

Question 5

Waardenburg syndrome

Answer 5

Dystopia canthorum ( lateral displacement of the inner canthi of the eyes, giving an appearance of a widened nasal bridge)
Pigmentary abnormalities of hair, iris, skin
SNHL (in 20-50%)
Abnl fnc of peripheral vestib system

4 subtypes

6 genes: 4 tf, 2 endothelins

Question 6

Usher syndrome

Answer 6

Retinitis Pigmentosa
Hearing impairment
+/- vestibular response

11 genes, best known is MYO7A (development and fnc of stereocilia)

Question 7

Alport syndrome

Answer 7

Renal dysfnc (hematuria, progressive failure)
Ocular abnlities (lenticonus & retinal flecks)
Initial high tone SNHL

Gene: COL4A3/4/5 (Collagen Type IV problems)

Question 8

Branchio-Oto-Renal syndrome

Answer 8

Branchial derived anomalies (cleft, cysts, or fistulas)
Oto (malformed pinna, preauricular pits, hearing loss - SNHL, CHL, or most often mixed HL)
Renal malformations (Hypoplastic kidneys and VUR)

Gene: EYA1 (tf)

Question 9

NF type II

Answer 9

B/l vestibular schwannomas
Meningioma
Schwannoma
Glioma
Neurofibroma in scalp
Juvenile subcapsular cataract

50% have hearing loss (usu u/l)
Molecular Dx in sporadic pts is less reliable bc a high % of mosaicism for mutations

Gene: NF2 product is Merlin (tsg)

Question 10

Jervell-Lange Nielsen syndrome

Answer 10

Prolonged QT (syncopal attacks and death)
SNHL

Gene: KCNE1, KVLQT1 (K channel)

Question 11

Treacher-collins synd

Answer 11

Hearing loss 2/2 malformations in middle and inner ear (cochlear/vestib apparatus, ossicles, EAC)
Craniofacial abnormalities (mandibulofacial dysostosis)

Gene: TCOF1 (ribosome biogenesis)

Question 12

Stickler syndrome

Answer 12

SNHL (mild-profound, progressive, all or high freq)
Possible eye findings (high myopia, cataracts, astigmatisms)
Arthropathy (spondyloepiphyseal dysplasia)
Cleft palate

Gene: collagen genes (3 -> 3 phenotypes)

Question 13

Usher Type IB-F

Answer 13

Hearing impairment: profound, congen
Vestib response: Absent
Onset of RP: 1st decade
Genes: MYO7A, USH1C, CDH23, PCDH15, SANS, 1 unknown

Question 14

Usher Type IIA/IIC

Answer 14

Hearing impairment: sloping, congen
Vestib response: Nl
Onset of RP: 1st or 2nd decade
Genes: USH2A, VLGR1, WHRN, 1 unknown

Question 15

Usher Type III

Answer 15

Hearing impairment: progressive
Vestib response: Variable
Onset of RP: Variable
Genes: USH3

Question 16

Work up of child with hearing loss

Answer 16

Consider labs (U/A, TFTs)
Imaging: CT to detect abnlities in bony structure of inner ear; MRI
Special tests for mutation screening
Perchlorate challenge test for Pendred
Special exams for syndromic:
-Ophtho exam (VA, fundo, electroretinogram for Usher)
-Vestibular fnc tests if c/o Sx
-Renal u/s (BOR synd)
-EKG (J-L-N synd)

Question 17

M/C inner ear abnlity in child w/ SNHL

Answer 17

Large vestibular aqueduct