Biology Reference
In-Depth Information
5. Syndromic Hearing Impairment
Hearing loss may occur in association with pathologies affecting virtually
any of the other organ systems, in which case it is called syndromic deaf-
ness. There are at least several hundred forms of syndromic hearing loss
that are postulated to account for approximately one-third of the cases of
genetic hearing loss (Gorlin et al. 1995) (Table 6.5). Deafness syndromes
and their loci are often named after the clinician(s) who discovered the syn-
drome, such as the Waardenburg syndrome named after Petrus J. Waar-
denburg. Alternatively, the name of the syndrome may be based upon the
phenotype, as in Branchial-Oto-Renal syndrome (BOR; Fig. 6.1 and Table
6.5). The name for a newly described deafness syndrome can be assigned
by the HUGO Nomenclature Committee before the gene is mapped. This
is because the new syndrome is, by definition, different from all other
described deafness syndromes. Nevertheless, two clinically distinct syn-
dromic forms of deafness may be due to allelic mutations in the same gene
(i.e., allelic heterogeneity). Examples of clinically distinct syndromes caused
by allelic mutations are the Marshall and Stickler syndromes, both of which
can be caused by mutations in
COL11A1
(see Section 5.1). Furthermore,
Waardenburg syndrome type I (MIM 193500), Waardenburg syndrome type
III (OMIM 148820) and Craniofacial-Deafness-Hand syndrome (OMIM
122880) are examples of allelic mutations of
PAX3
(Asher et al. 1996).
Identification and analysis of syndromic hearing loss genes should
provide insight into all types of hearing impairment, including nonsyn-
dromic hearing loss. For example, there are alleles of genes causing syn-
dromic hearing loss that are associated with nonsyndromic cases. Mutations
of the
MYO7A
gene can cause nonsyndromic deafness
DFNA11
and
DFNB2
, as well as hearing loss with retinitis pigmentosa in Usher syndrome
type IB (Liu et al. 1997b; Liu et al. 1997c; Weil et al. 1995; Weil et al. 1997).
Similarly, mutations of PDS may cause nonsyndromic deafness
DFNB4
or
Pendred's syndrome (see Section 5.2) (Everett et al. 1997; Li et al. 1998).
There will likely be additional examples of allelism of syndromic with
nonsyndromic hearing loss mutations as hearing loss genes continue to be
identified.
Many types of syndromic hearing loss are likely to share similar patho-
genetic mechanisms in the inner ear and other affected organ systems.
Elucidation of the pathogenesis of auditory dysfunction may therefore be
achieved by analogy to the etiopathogenesis of disease processes occurring
in the other organ systems. This is especially useful given the paucity of
auditory histopathologic data for the vast majority of genetic sensorineural
hearing loss. For example, the well characterized basement membrane
pathology observed in the progressive nephritis of Alport syndrome (sen-
sorineural hearing loss in association with progressive nephritis) may share
some pathogenetic features with the cochlea, and could facilitate our under-
standing of how auditory dysfunction occurs in these patients.
