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INTRODUCTION

ESSENTIALS OF DIAGNOSIS

  • In most cases, sensorineural hearing loss of unknown origin.

  • Positive family history often present.

  • Vestibular symptoms possible, but more seldom.

  • In syndromic cases, associated with other clinical abnormalities.

General Considerations

Hearing loss is the most common sensory deficit in humans. The prevalence of congenital hearing loss in newborns is approximately 1 to 3 cases per 1000. More than 60% of these prelingual cases (ie, hearing loss before the acquisition of speech) are attributed to genetic causes. A further 1 in 1000 children becomes deaf before adulthood. In patients over 60 years of age, approximately half show a hearing loss > 25 dB HL. A large percentage of these populations is estimated to be likely affected by genetic influences, although age-related epidemiologic studies of the genetic contribution to hearing loss are not available. Finally, more than 100 deafness genes are believed to exist in nonsyndromic hearing loss. These figures illustrate the impact of hearing loss on the public health system and the importance of genetic factors. Hereditary hearing impairment (HHI) is constantly and rapidly evolving, in part due to new technologies such as next-generation DNA sequencing.

Classification

The most common and useful distinction in HHI is syndromic versus nonsyndromic hearing impairment. Seventy percent of HHIs are nonsyndromic, whereas a minority of 15% to 30% are syndromic (Figure 56–1).

Figure 56–1

Causes and distribution of genetic deafness.

A. Nonsyndromic Hereditary Hearing Impairment

Nonsyndromic HHI is classified by the mode of inheritance. Autosomal-recessive transmission (designated by prefix DFNB) is implicated in approximately 80% of cases, autosomal-dominant transmission (DFNA) is present in approximately 20% of cases, and X-linked (DFN) and mitochondrial transmission are responsible for < 2% of cases (see Figure 56–1). A single gene, GJB2 (Gap-Junction Beta 2 encoding for connexin 26), has emerged to be the most common cause of recessive deafness; up to 40% of the onset of sporadic prelingual hearing impairment can be attributed to defects in this gene both in Europe and the United States. The prevalence is higher in southern Europe than in northern Europe, mainly owing to 1 single gene mutation, c.35delG. In a stretch of 6 guanines extending from position 30 to 35, 1 base pair is deleted. The high incidence of this mutation seems to be due to a common ancestor. Together with 5 other common mutations (R134W in Ghana, c.167delT in Ashkenazi Jews, c.235delC and V37I in Southeast Asia, and W24X in the Indian population), GJB2-related hearing loss accounts for the most prevalent single cause of congenital deafness in almost 70% of the world’s population. However, heterozygosity (ie, multiple genes responsible) with more than 100 known mutations and highly variable auditory phenotype complicate the clinical interpretation.

Mitochondrial genes constitute a small and unique group. Inheritance ...

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