Congenital deafness occurs at a frequency of 1:1000 newborns. This is a heterogeneous
group - there are many causes of deafness of which 2/3 are genetic and 1/3 are not.
Non-genetic causes usually
manifest as unilateral, asymmetric hearing impairment and are usually caused by
environmental factors such as frequent use of intravenous aminoglycoside-type antibiotics,
premature birth, prolonged intensive care, viral infection in the first months following
birth (particularly mumps and CMV), intrauterine infection with CMV or other viruses, brain damage at birth, meningitis,
Genetic causes are also diverse. The main types of inheritance patterns are ">autosomal
recessive - 83%,
autosomal dominant - 10%, and
X-linked - 5%. Recently, however, it has been shown that deafness
can also be transmitted by mitochondrial inheritance - individuals with specific
mutations in the mitochondrial genome can have an extreme sensitivity to several
medications, especially aminoglycoside antibiotics, which can cause deafness following
the administration of a single low dose. It is estimated that mitochondrial inheritance accounts for
approximately 2% of all cases of hereditary deafness.
In cases that have a genetic cause, the hearing impediment is usually bilateral
In 83% of cases the inheritance is autosomal recessive, and the parents of an affected
child have a 25% risk in each pregnancy for having another child with a similar
In all cases where there is a family history, it is important for the geneticist
to establish the inheritance pattern and hence the risk to the various family members
of having a child with a hearing impediment.
In some cases the hearing impairment is part of a syndrome, with other organs also
being involved. In retinitis pigmentosa (a disorder of vision) both the eye and
the ear are involved, and there are other syndromes where hearing impairment is
associated with white hair tips, mental retardation, skin spots, kidney diseases,
etc. The presence of such signs and symptoms will assist the geneticist in making
an accurate diagnosis, based on which he will be able to determine the risk of recurrence
and decide which tests should be performed before and during a subsequent pregnancy.
In recent years there has been great progress in identifying the genes that are
responsible for deafness. There are very many genetic causes, and within each type
of inheritance pattern there are a large number of different genes that cause hearing
impairment. For example, more than 20 genes are currently known to be responsible
for autosomal recessive deafness, so that if two people with this type of deafness
marry, as long as the genes carried by each of the parents are different, they can
have children with perfect hearing. This is also the case for other inheritance
Molecular testing is as yet not available for all of the genes concerned. However,
about 40% of autosomal recessive hearing defects are a result of known, recognized
mutations in the Connexin 26 gene.
There is one specific mutation that is common among Ashkenazi Jews - this is 167delT,
a deletion of a single nucleotide T at position 167 of the gene. More recently it
has been found that another common mutation (a deletion of part of the gene) in
a nearby gene called Connexin 30, can also cause a malfunction of the Connexin 26
gene. Therefore a couple where both partners carry a mutation in Connexin 26, or
where one partner carries a mutation in Connexin 26 and the other a mutation in
Connexin 30, can have a child who is deaf, with a risk in each case of 25%. Because
of this, both the testing of deaf individuals of Ashkenazi origin and the screening
of healthy Ashkenazi Jews for carrier status should include at least these 2 mutations
in Connexin 26 and Connexin 30.
In Connexin 26 there is another mutation that is common in all ethnic groups - 35delG
(a deletion of a single nucleotide G at position 35 of the gene).
The cause of the deafness can be established in at least 40% of families with autosomal
recessive hearing defects by performing a relatively simple test. In such cases
the parents are given appropriate counseling and are offered prenatal diagnosis
or diagnosis right after birth.
It is important to test for mutations in the Connexin 26 gene (and also in the Connexin
30 gene in Ashkenazim) in individuals with hearing defects, and if one is found,
the carrier status of the parents can be tested. However, because of the good prognosis,
this is not mandatory. This is also the reason for not recommending general screening
for non-syndromic hearing loss, although by means of a relatively easy test, 1:30
individuals will be found to be a carrier of a mutation in Connexin 26 and/or Connexin
Tests are also available nowadays for many other syndromes associated with deafness,
including for the specific mitochondrial mutation that predisposes to drug (aminoglycoside)
induced deafness, etc.
The importance of early diagnosis
In recent years there have been significant advances in the management and treatment
of hearing-impaired children. A cochlear implant can be inserted, and this is very
effective, especially if carried out in early childhood. This is why early diagnosis
Hearing loss in adulthood
Hearing impairment in adulthood is common - over a certain age, 1/3 of the population
have hearing impairments. Appropriate tests for these individuals are on the whole
not available, and, of course, prenatal testing in such cases is of lesser importance.
The geneticist's role
In genetic counseling,
the presence or absence of a syndrome is ascertained, the probability for a genetic
or environmental cause is determined, and if a genetic cause is identified, assessment
of the risk of having an infant with a problem and decision as to which tests should
be performed before and during a subsequent pregnancy.