Genetics and Hearing Loss

GENETICS AND HEARING LOSS

Submitted by Kathleen Corbin, M.A., CCC-A, Audiologist

for the

ISHA Fall Conference, September 21, 2013

Over one in every 500 infants has or will develop a hearing loss in early childhood

GENETIC HEARING LOSS – approx. 50% to 60% of all with hearing loss

MODE OF TRANSMISSION

·  80% Recessive

·  15% Dominant

·  2% x-linked

·  2% Mitochondrial

CATEGORIES OF GENETIC HEARING LOSS

·  Non-Syndromic (70%)

·  Syndromic (30%)

NON-SYNDROMIC

Common mutation sites

·  GJB2 (Gap Junction Protein, Beta 2) gene (Causal factor of 40% of non-syndromic hearing

loss) –

·  Myosin VI

·  TECTA

GENETICS and HEARING LOSS

K. Corbin, p. 2

SYNDROMIC DEAFNESS

·  More than 600 different syndromes identified

·  Auditory Profile

·  Conductive, sensor neural or mixed

·  Unilateral or bilateral

·  Symmetrical or asymmetrical

·  Progressive or stable

COEXISTENT DEFICITS

·  Cardiovascular

·  Renal

·  Neurologic

·  Pulmonary

·  Ophthalmic

·  Orthopedic

·  Endocrine

·  Immunologic

SYNDROMIC HEARING LOSS

INHERITED VIA RECESSIVE TRANSMISSION

USHER SYNDROME

·  Most common eye/ear disorder

·  Estimated 10% of all children with SNHL

·  Hearing loss

§  Type I: Absent vestibular function

§  Severe to Profound SNHL

§  Type II: Moderate to Severe SNHL

§  Type III: Progressive SNHL

·  Retinitis Pigmentosa

PENDRED SYNDROME

·  Estimated at 5% of all children with hearing loss

·  Profound sensor neural hearing loss (cochlear)

·  Vestibular Dysfunction

·  Thyroid defect, goiter

GENETICS and HEARING LOSS

K. Corbin, p.3

JERVELL and LANGE-NIELSON SYNDROME

·  Profound SNHL

·  Cardiac abnormality

·  Recurrent drop attacks

·  Sudden death

INHERITED VIA DOMINENT TRANSMISSION

WAARDENBURG SYNDROME

·  Estimates of 2.3% of all children with hearing loss

·  Type I appearance of widened nasal bridge -20% with SNHL;

·  Type II no appearance of widened nasal bridge - 50% with hearing loss

·  Pigmentary abnormalities

·  White forelock

·  Partial albinism

·  Early graying

TREACHER COLLINS

·  Conductive hearing loss

·  Craniofacial anomalies

·  Eyelid colobomas

STICKLER SYNDROME

§  More prevalent in the Midwest region of the United States

§  Hearing loss due to Eustachian tube dysfunction secondary to palatal anomalies; SNHL which may be progressive or conductive anomalies have been noted

§  Flattening of the facial profile

§  Cleft palate

§  Myopia/retinal detachment/cataracts

§  Neuropathy

BRANCHIO-OTO-RENAL SYNDROME (BOR)

·  Estimated in 2% of all children with profound SNHL

·  Hearing loss is present in 75% of patient with BOR

·  CHL (30%)

·  SNHL (20%)

·  Mixed (50%)

·  Malformation of the pinnate and preauricular pits

·  Renal anomalies are markedly varied and may be asymptom

GENETICS and HEARING LOSS

K. Corbin, p.4

NEUROFIBROMATOSIS II

·  Vestibular schwannomas with secondary hearing loss and other intracranial tumors

·  45% - 50% have accompanying hearing loss

·  75% have unilateral hearing loss

·  Hearing loss is neural or central

INHERITED VIA X-LINKED TRANSMISSION

Alport Syndrome

·  Incidence estimated at 1% of all children with hearing loss

·  Progressive SNHL (High-frequency; Cochlear)

·  Progressive Nephritis

·  Lens Abnormalities

·  Renal and Hearing impairment usually manifest in adolescence or early adult years

INHERITED VIA MITOCHONDRIAL DISORDERS

Kearns-Sayre syndrome

·  Incidence unknown

·  Neuromuscular disease

·  SNHL

NON-GENETIC HEARING LOSS (30%)

Maternal Influences

·  Infection – viral or bacterial

·  Substance abuse

·  Environmental exposure

Birth Complication

·  Respiratory distress/perinatal asphyxia

·  Hyperbilirubinemia

·  Hemorrhage perinatal or intraventricular

COMBINATION OF GENES AND ENVIRONMENT (10%)

·  Ototoxicity-Induced SNHL from Aminoglycoside Exposure

·  Noise-Induced SNHL from Excessive Noise Exposure