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

Notes

The information in this outline was last updated in 2002.