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 Common causes of Genetic hearing loss 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 Notes The information in this outline was last updated in 2002.