Biology Reference
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between 30 and 45 years of age. A segregation analysis that included 104
of the cases showed that 71% were genetic, while the remainder were
sporadic, being determined largely by nongenetic causes associated with a
negligible chance of recurrence within families. Among the genetic cases,
4.2% were associated with distinctive clinical features that permitted
the diagnosis of a syndrome, while 89% were nonsyndromic-recessive and
6.8% nonsyndromic-dominant. The reproductive fitness of these cases was
estimated to be 0.4 relative to hearing siblings.
The existence of etiologic heterogeneity with both genetic and environ-
mental causes has been a consistent feature of studies of deafness. Among
genetic cases, recessive transmission predominates, but the observed and
adjusted frequencies of consanguinity are much higher than would be
expected from the incidence of the phenotype, yielding estimates of the
number of recessive loci that have ranged from 36 to 103, or higher (Chung
and Brown 1970; Morton 1991). Data on marriages among the deaf show
strong evidence for assortative mating in many but not all countries (e.g.,
India). When DxD matings have been studied, segregation analysis shows
that relatively few couples are capable of producing only affected offspring,
a finding that is inconsistent with the assumption that most cases of deaf-
ness are caused by recessive mutations at a single locus. Rose (1975; 1977)
showed that the observed proportion of non-complementary matings was
consistent with the assumption that recessive deafness is caused by equally
frequent mutations at about 10 loci. The fact that higher estimates are
obtained from consanguinity analysis indicates that the recessive pheno-
types are not equally frequent, a conclusion that has been amply verified
by recent discovery of the high proportion of recessive deafness that can
be attributed to mutations in the connexin 26 gene.
3. Genetic Epidemiology of Deafness
The incidence of profound deafness in the United States is about 0.8 per
1,000 births (Bodurtha and Nance 1988). If lesser degrees (>30 dB) of loss,
or unilateral or conductive losses are included, the incidence at birth or early
infancy may be as high as 1.5-6 per 1,000. These rates can be influenced
greatly by temporal or geographic variation in the frequency of recognized
environmental causes including pre- or postnatal infections, such as rubella,
cytomegalic inclusion body virus (CMV), otitis media, meningitis, prematu-
rity, trauma, kernicterus, and exposure to ototoxic drugs. Despite the intro-
duction of rubella immunization programs, the congenital rubella syndrome
remains an important cause of deafness. Studies of infants with congenital
deafness have also suggested that as many as 12% may be attributable to
prenatal CMV infections (Peckham et al. 1987). Aminoglycoside ototoxic-
ity provides a good example of geographic variation in the causes of deaf-
ness. Because of the widespread use of these antibiotics in infancy and
