# 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.