Handbook of Genetic Counseling/Hearing loss - Unknown Cause

Hearing loss - Unknown Cause

Introduction

 * What have you been told about coming to genetics today?
 * What information have you been given already?
 * Have you done any research on your own? What have you found out?
 * What concerns or questions would you like to have answered today?
 * Outline session

Medical History

 * Complete intake
 * How was his hearing loss first found?
 * Eye problems?
 * Development
 * Age first walked? Sat up?
 * EKG?
 * CT scan
 * Kidney problems?
 * Infections?
 * Neurological problems? Seizures?
 * Birthmarks? Rashes?

Family History

 * Complete pedigree
 * Anyone with deafness? Hearing loss?
 * Eye problems?
 * White forelock?
 * Mental retardation?
 * Kidney problems?

Genetics of Hearing loss

 * 1/2000 to 1/1000 children born with profound hearing loss
 * 50% hearing loss has a genetic cause
 * 1/3 related to syndrome
 * 2/3 nonsyndromic
 * 76% recessive genes
 * 20% dominant genes
 * 4% X-linked genes
 * Hearing loss increases with age
 * Impact of genetics and environment
 * Empiric Risks (if no diagnosis can be established)
 * Hearing parents with one deaf child
 * 18% risk of deafness in future children
 * offspring of deaf person and hearing person
 * 10% risk of deafness
 * deaf couple without AD hearing loss
 * 15% risk of deafness in children
 * child of hearing sib of deaf proband and deaf person
 * 1/200 risk for deafness

Management

 * Frequent audiologic evaluations to document stability or progression of hearing loss
 * Determine appropriate habilitation option
 * Hearing aids
 * Cochlear implants
 * Educational intervention

Syndromic Hearing loss
(Accounts for 30% prelingual deafness)
 * Autosomal Recessive
 * Usher Syndrome
 * Congenital sensorineural hearing loss
 * Type 1
 * Severe to profound hearing loss
 * Abnormal vestibular function
 * Delayed walking and sitting
 * Type 2
 * mild to severe hearing loss
 * normal vestibular function
 * Type 3
 * Progressive hearing loss
 * Progressive deterioration of vestibular function
 * Retinitis Pigmentosa
 * Apparent after first decade of life
 * Electroretinography can identify abnormalities in photoreceptor function in children as young as 2 - 4
 * Pendred Syndrome
 * Most common type of AR syndromic hearing loss
 * Congenital severe to profound SNHL
 * Abnormality of bony labyrinth that can be diagnosed with CT scan
 * Euthyroid goiter
 * Develops in puberty to adulthood
 * located at 7q22-q13
 * mutations in this gene can also cause nonsyndromic deafness
 * Jervell and Lange-Nielsen syndrome
 * Congenital deafness
 * Prolongation of QT wave on ultrasound
 * Can be detected by EKG
 * Syncopal episodes can cause sudden death
 * Caused by mutations in two different genes
 * Genetic testing not recommended in evaluation of deaf children
 * Recommended for those at high risk
 * Refsum disease
 * Severe progressive SNHL
 * Retinitis Pigmentosa
 * Caused by faulty phytanic acid metabolism
 * Can be controlled with dietary modification
 * Diagnosed by serum concentration of phytanic acid
 * Autosomal Dominant
 * Waardenburg syndrome
 * Variable degrees of SNHL
 * Pigmentary abnormalities of the skin, hair, and eyes
 * Type 1 - lateral displacement of inner canthus (PAX3 gene - clinical testing)
 * Type 2 - no displacement of inner canthus (MITF gene - research testing)
 * Type 3 - upper limb abnormalities (PAX3 gene - clinical testing)
 * Type 4 - Hirschprung disease (EDNRB, EDN3, SOX10 genes - research testing)
 * Branchiootorenal Syndrome
 * Conductive, sensorineural, and mixed hearing loss
 * Brachial cleft cysts or fistula
 * External ear malformation (prearicular pits)
 * Renal anomalies
 * 20-30% have mutation in EYA1 (locus 8q13) - testing available
 * Stickler Syndrome
 * Progressive SNHL
 * Cleft palate
 * Spondyloepiphyseal dysplasia causing osteoarthritis
 * Genetic causes:
 * STL1(COL2A1)
 * STL2 (COL11A2)
 * STL3 (COL11A1)
 * STL1 and STL3 are associated with severe myopia
 * Clinical testing available
 * Neurofibromatosis type II
 * Bilateral vestibular schwannomas causing hearing loss
 * Generally begins in 3rd decade
 * Hearing loss is generally unilateral and gradual
 * MRI to diagnose
 * Other tumors are associated
 * Molecular testing available
 * X-linked
 * Alport syndrome
 * Progressive sensorineural hearing loss (variable severity)
 * Generally begins after 10 years of age
 * Progressive renal disease
 * Ophthalmologic findings
 * 85% X-linked, AR and AD forms also identified
 * DFN1 (Xq22)
 * Progressive, postlingual hearing loss
 * Visual disability
 * Dystonia
 * Fractures
 * Mental retardation
 * Mitochondrial syndromes

Nonsyndromic Hearing Loss
(70% hereditary hearing loss)
 * Autosomal Recessive
 * 50% families DFNB1
 * 50% other multiple loci
 * many different genes - many in only one family
 * Autosomal Dominant
 * Many different genes
 * No one gene causes majority of cases
 * X-linked
 * DFN3 (Xq21.1)
 * Mixed hearing loss
 * Stapedial fixation
 * Gene called POU3F4
 * Multiple other genes
 * Mitochondrial
 * Multiple genes
 * Low penetrance
 * Possible environmental factors

Psychosocial Issues

 * Deaf child born to hearing parents
 * How did you feel when you first found out?
 * How have your feelings changed?
 * How have other family members reacted?
 * Have you been in contact with any other families?
 * Have you been in contact with any support groups?
 * What are your biggest concerns at the moment?

Resources

 * American Society for Deaf Children
 * PO Box 3355
 * Gettysburg, PA 17325
 * Phone: 800-942-ASDC (parent hotline)
 * Email: ASDC1@aol.com
 * Web: www.deafchildren.org
 * National Association of the Deaf
 * 814 Thayer
 * Silver Spring, MD 20910
 * Phone: 301-587-1788
 * Email: NADinfo@nad.org
 * Web: www.nad.org