A genetic evaluation can assist in identifying the etiology of a hearing loss when physical and laboratory assessments fail to do so.

It is the geneticist who provides the diagnosis of inherited diseases. The medical geneticist is responsible for evaluating and interpreting:

• The comprehensive family history data (three to four generations) with attention to consanguinity, paternity and hearing status of the parents and siblings;

• The inheritance patterns of the hearing loss (autosomal dominant, autosomal recessive, X-linked, or mitochondrial);

• Country of origin;

• Audiometric characteristics of any family members with hearing loss such as age at onset, progression and type.

As part of the evaluation the geneticist conducts a clinical evaluation paying particular attention to visual, facial, endocrine, cardiac, renal or integumentary changes that may be associated with a syndromic type of hearing loss.

The geneticist also orders and interprets the genetic tests. GJB2 or Connexin 26 mutation screening should be obtained by sequence analysis. A negative test does not rule out a genetic etiology, but a positive test confirms the cause and eliminates the need for further expensive and possibly more invasive tests.

Genetic counseling should be conducted by trained professionals who are sensitive to the ethical, cultural and socioeconomic status of the family. The overall purpose of the counseling is to assure that the family understands the results of the testing. Based on the outcome of the comprehensive evaluation other types of professionals may be consulted, especially in syndromic hearing loss.

Modes of Inheritance

There are varying ways that genes that cause congenital hearing loss can be inherited. Determination of the mode of inheritance is a critical factor in the genetic counseling that is provided to the family.

Profound congenital hearing loss is estimated to occur in about 1 in 1,000 births. Approximately 50% of the cases are thought to be due to environmental factors and the remainder to genetic causes (American College of Medical Genetics (ACMG), 2002)

Nonsyndromic Inheritance Patterns

Approximately 70% of the congenital hearing loss cases associated with genetic factors are classified as nonsyndromic. The hearing loss is not associated with a syndrome and may be caused by a single gene mutation. These conditions are usually inherited in one of several straightforward patterns and are subdivided by the mode of inheritance (ACMG, 2002).

Syndromic Inheritance Patterns

In the 70% of congenital cases associated with genetic factors, 30% are syndromic, where deafness can be diagnosed because of associated clinical findings (Gorlin, Toriello, Cohen, 1995). The auditory pathology varies widely among the more than 400 types of syndromic hearing loss and includes both conductive and sensorineural deficits that can be unilateral or bilateral, progressive or stable or symmetrical or asymmetrical (Resendes, Williamson, Morton, 2001).

The following are examples of some of the more common syndromes associated with syndromic hearing loss as well as links to information on the National Organization of Rare Diseases (NORD) website:

Alport Syndrome

Branchial-Oto-Renal (BOR) Syndrome

Jervell and Lange-Nielsen Syndrome

Norrie Syndrome/Disease

Usher Syndrome

Waardenburg Syndrome

References

American College of Medical Genetics. (2002). “ Genetics evaluation guidelines for the etiologic diagnosis of congenital hearing loss”, 4(3), 1-12.

Gorlin RJ, Toriello HV, Cohen MM. Hereditary hearing loss and its syndromes. New York: Oxford University Press, 1995.

Resendes, BL, Williamson RE, Morton CC. (2001). At the Speed of Sound: Gene Discovery in the Auditory Nervous System, American Journal of Human Genetics, 60: 923-935.