Your Genes and Hearing Loss
One of the most common birth defects is hearing loss or deafness
(congenital), which can affect as many as three of every 1,000 babies
born. Inherited genetic defects play an important role in congenital
hearing loss, contributing to about 60 percent of deafness occurring in
infants. Although exact data is not available, it is likely that
genetics plays an important role in hearing loss in the elderly.
Inherited genetic defects are just one factor that can lead to hearing
loss and deafness, both of which may occur at any stage of a person’s
lifespan. Other factors may include: medical problems, environmental
exposure, trauma, and medications.
The most common and useful distinction in hearing impairment is syndromic versus non-syndromic.
- Non-syndromic hearing impairment accounts for the vast majority
of inherited hearing loss, approximately 70 percent. Autosomal-
recessive inheritance is responsible for about 80 percent of cases of
non-syndromic hearing impairment, while autosomal-dominant genes cause
20 percent, less than two percent of cases are caused by X-linked and
mitochondrial genetic malfunctions.
- Syndromic(sin-DRO-mik) means that the hearing impairment is
associated with other clinical abnormalities. Among hereditary hearing
impairments, 15 to 30 percent are syndromic. Over 400 syndromes are
known to include hearing impairment and can be classified as: syndromes
due to cyotgenetic or chromosomal anomalies, syndromes transmitted in
classical monogenic or Mendelian inheritance, or syndromes due to
multi-factorial influences, and finally, syndromes due to a combination
of genetic and environmental factors.
Variable expression of different aspects of syndromes is common. Some
aspects may be expressed in a range from mild to severe or different
combinations of associated symptoms may be expressed in different
individuals carrying the same mutation within a single pedigree. An
example of variable expressivity is seen in families transmitting
autosomal dominant Waardenburg syndrome. Within the same family, some
affected members may have dystopia canthorum (an unusually wide nasal
bridge due to sideways displacement of the inner angles of the eyes),
white forelock, heterochromia irides (two different-colored irises or
two colors in the same iris), and hearing loss, while others with the
same mutation may only have dystopia canthorum.
How do genes work?
Genes are a road map for the synthesis of proteins, which are the
building blocks for everything in the body: hair, eyes, ears, heart,
lung, etc. Every child inherits half of its genes from one
parent and half from the other parent. If the inherited genes are
defective, a health disorder such as hearing loss or deafness can
result. Hearing disorders are inherited in one of four ways:
- Autosomal Dominant Inheritance:
For autosomal dominant disorders, the transmission of a rare allele of
a gene by a single heterozygous parent is sufficient to generate an
affected child. A heterozygous parent has two types of the same gene
(in this case, one mutated and the other normal) and can produce two
types of gametes (reproductive cells). One gamete will carry the mutant
form of the gene of interest, and the other the normal form. Each of
these gametes then has an equal chance of being used to form the
offspring. Thus the chance that the offspring of a parent with an
autosomal dominant gene will develop the disorder is 50 percent.
Autosomal dominant traits usually affect males and females equally.
- Autosomal Recessive Inheritance:
An autosomal recessive trait is characterized by having parents who are
heterozygous carriers for mutant forms of the gene in question but are
not affected by the disorder. The problem gene that would cause the
disorder is suppressed by the normal gene. These heterozygous parents
(A/a) can each generate two types of gametes, one carrying the mutant
copy of the gene (a) and the other having a normal copy of the gene
(A). There are four possible combinations from each of the parents,
A/a, A/A, a/A, and a/a. Only the offspring that inherits both mutant
copies (a/a) will exhibit the trait. Overall, offspring of these two
parents will face a 25 percent chance of inheriting the
disorder.
- X-linked Inheritance: A male
offspring has an X chromosome and a Y chromosome, while a female has
two copies of the X chromosome only. Each female inherits an X
chromosome from her mother and her father. On the other
hand, each male inherits an X chromosome from his mother and a Y
chromosome from his father. In general, only one of the two X
chromosomes carried by a female is active in any one cell while the
other is rendered inactive. This is why when a female inherits a
defective gene on one X chromosome, the normal gene on the other X
chromosome can usually compensate. As males only have one copy of the X
chromosome, any defective gene is more likely to manifest into a
disorder.
- Mitochondrial Inheritance:
Mitochondrias, small powerhouses within each cell, also contain their
own DNA. Interestingly, the sperm does not have any mitochondria, and
consequently, only the mitochondria in the egg from the mother can be
passed from one generation to the next. This leads to an interesting
inheritance pattern where only affected mothers (and not affected
fathers as their sperms do not have mitochondria) can pass on a disease
from one generation to the next. Sensitivity to aminoglycoside
antibiotics can be inherited through a defect in mitochondrial DNA and
is the most common cause of deafness in China!
In the last decade, advances in molecular biology and genetics have
contributed substantially to the understanding of development,
function, and pathology of the inner ear. Researchers have identified
several of the various genes responsible for hereditary deafness or
hearing loss, most notably the GJB2 gene mutation. As one of the most
common genetic causes of hearing loss, GJB2-related hearing loss is
considered a recessive genetic disorder because the mutations only
cause deafness in individuals who inherit two copies of the mutated
gene, one from each parent. A person with one mutated copy and one
normal copy is a carrier but is not deaf. Screening tests for the GJB2
gene are available for at risk individuals to help them determine their
risk of having a child with hearing problems.
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