Causes of Hearing Loss

Basic Genetics
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What Are the Most Common Forms of Genetic Hearing Loss?

Of the 50% of the genetic forms of hearing loss, an estimated 70% are due to recessive
causes, about 15% have a dominant cause; and the remaining 15% include all the other forms
of inheritance.

GENETIC
RECESSIVE 70%

NON-GENETIC AND
  UNKNOWN
DOMINANT 15%
OTHER GENETIC 15%

Genetic scientists subdivide genetic hearing loss into two general categories: "Non-
Syndromic" (meaning hearing loss and nothing else) and "Syndromic" (meaning hearing loss
with other clinical findings). By far, the more common is Non-syndromic hearing loss which
includes 2/3 of all genetic hearing losses.

NON-
SYNDROMIC
SYNDROMIC
 
   

RECESSIVE RECESSIVE NON-GENETIC AND

DOMINANT DOMINANT UNKNOWN
OTHER OTHER
GENETIC GENETIC

What is the Most Common form of genetic hearing loss?

One gene, known as Connexin 26 (abbreviated CX26), is estimated to be responsible for half
of all the recessive cases of hearing loss. There are over 400 known genetic causes involving
hearing loss. CX26 alone is responsible for about 1/3 of all the cases of genetic hearing loss!

NON-
SYNDROMIC
SYNDROMIC
 

  CONNEXIN-
26
RECESSIVE NON-GENETIC AND
RECESSIVE UNKNOWN
DOMINANT DOMINANT
OTHER OTHER
GENETIC GENETIC

What are the Next Most Common Forms of Genetic Hearing Loss?
Since CX26 accounts for about 1/3 of all cases of genetic hearing loss, that leaves about 1/3
of all cases as non-syndromic (this includes all types of inheritance) with the remaining 1/3 as
syndromic. Among the remaining 1/3 of non-syndromic cases of genetic hearing loss, 13
dominant and 8 other recessive genes have been described.
What are the Common Dominant Syndromic Hearing Loss Types?
The following descriptions are only a brief review. Medical professionals can guide you for
further information. About 5% of all hearing loss is dominant syndromic in nature.
http://www.familyvillage.wisc.edu/index.htmlx

Waardenburg Syndrome - The hearing loss in Waardenburg Syndrome may be present in

one or both ears and is a sensorineural type of loss. The striking features of Waardenburg
syndrome may include: premature graying hair, white forelock, fused eyebrows (synophrys),
two different-colored eyes (heterochromia irides, usually bright blue and brown), widely-
spaced eyes (hypertelorism), high nasal bridge, under-developed nose tip (hypoplastic alae
nasia) and partial albinism.
http://www.boystownhospital.org/Hearing/info/genetics/syndromes/waardenburg.asp
http://www.nidcd.nih.gov/health/hearing/waard.asp

Branchio-Oto-Renal (BOR) Syndrome - The hearing loss in BOR Syndrome is conductive,

sensorineural or mixed. Cysts (or pits) can be found on the neck (branchial cleft) or in front
of the outer ear (prearicular). The outer ear (pinna) may be malformed and stapes fixation,
inner ear malformations and/or enlarged vestibular aqueducts may be present. A major
medical concern with BOR are the associated renal (kidney) problems, which could be life
threatening. http://www.boystownhospital.org/Hearing/info/genetics/syndromes/bor.asp

Neurofibromatosis Type II (NFII) - The hearing loss in NFII is progressive sensorineural

leading to possible deafness. Café-au-lait (coffee with cream-colored) spots may appear on
the skin, with freckling and cataracts. Acoustic tumors may grow on the VIIth cranial nerve,
causing hearing loss. Tumors may also grow on other nerves. http://www.nfinc.org/  
www.nf.org
http://www.nlm.nih.gov/medlineplus/neurofibromatosis.html#nlmnihresources

Stickler Syndrome - The hearing loss in Stickler Syndrome is

usually conductive, although some losses may be mixed or
sensorineural. Progressive hearing loss has also been reported.
There are three syndrome types. All are related to altered
expression of a collagen/connective tissue gene. Associated features
may include: cleft palate, downward-placed tongue (glossoptosis),
small jaw (micrognathia), under-developed midface, progressive
severe near-sightedness (myopia), cataracts, retinal
detachment/degeneration, bone/joint disorders, early adult-onset
arthritis, and middle ear bone (ossicular) malformations.
http://www.sticklers.org/sip/

Treacher-Collins Syndrome - The hearing loss in Treacher-

Collins is conductive. Striking facial features include cleft palate,
down-slanting eye-slit openings (palpebral fissures), unusual pupil openings (coloboma),
under-developed cheek bones (malar hypoplasia), absent/malformed outer ears, absent
(atresia) or narrow (stenosis) ear canals, skin tags in front of the ear (prearicular), teeth
alignment problems (malocclusion) and possible balance (vestibular) problems.

What are the Common Recessive Syndromic Hearing Loss Types?

Recessive Syndromic hearing loss accounts for about 20% of all types of genetic hearing
loss.
Usher Syndrome - There are three (3) types of Usher syndrome with different types of
hearing loss. Type I has congenital, profound, sensorineural hearing loss. And vestibular
dysfunction. Type II has a downward-sloping, sensorineural hearing loss. Type III has a
progressive sensorineural hearing loss and variable vestibular dysfunction. All types have
progressive vision loss. http://www.nidcd.nih.gov/health/hearing/usher.asp

Alport Syndrome - Hearing loss in Alport syndrome may be sensorineural, conductive or

mixed and may be progressive. Alport syndrome may also be X-linked (linked to sex-
chromosome inheritance). Other features include kidney problems (nephritis), near-
sightedness (myopia) or cataracts, and palate abnormalities.
http://www.cc.utah.edu/~cla6202/ASHP.htm

Jervell and Lange-Nielson Syndrome - The hearing loss in JL-N

syndrome is sensorineural. The other major finding in JL-N is an
abnormal heart rhythm (long Q-T), which could lead to fainting spells and
possible sudden death. These might be mistaken for seizures. These
abnormal heart rhythms are successfully treated with medication (beta
blockers).

Pendred Syndrome - The hearing loss in Pendred syndrome may be

mixed or sensorineural and may be progressive. Pendred Syndrome may
have an associated goiter,and variable inner ear malformations (Mondini
malformation with or without enlarged vestibular aqueduct).
http://www.medicinenet.com/Script/Main/Art.asp?
li=MNI&ArticleKey=9460

What are Some Less-Common Syndromic Hearing Loss Types?

CHARGE Syndrome - The letters in CHARGE stand for Coloboma, Heart, Atresia of the
choanae, Retardation of growth and development, Genital and urinary abnormalities, and Ear
abnormalities. CHARGE is thought to be multifactorial. The hearing loss may be conductive,
sensorineural or mixed and range from mild to profound. In addition to the features in the
name, there may be partial facial paralysis, cleft palate, cleft lip, kidney problems, and
feeding problems due to an opening between the windpipe and the feeding tube.
http://www.chargesyndrome.org/

X-Linked Congenital Stapes Fixation with Perilymph Gusher - For boys with this
syndrome, the hearing loss is mixed and may be progressive. Females who carry this gene
may have mild, mixed or sensorineural hearing loss. Boys with this gene have a further risk
of increased hearing loss if middle ear surgery is performed to correct the stapes fixation
because the surgery may result in massive and sudden loss of inner ear fluid (perilymph).

Mitochondrial Conditions
Mitochondria are structures in the cell that produce the energy that cells
need to survive. Neither the mitochondria nor the cell can exist without
the other. Interestingly, mitochondria have a separate set of genes that are
not part of the cell's genes. This is because mitochondria originally came
from energy-producing bacteria that merged with the cell. Anything that
affects bacteria could also affect the function of the cell's mitochondria,
which might eventually affect the cell's energy source. Changes in the mitochondrial genes
can also result in syndromes involving hearing loss.

 Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like Episodes

(MELAS) - About 30% have sensorineural hearing loss. The findings are
highly variable and may include: intermittent vomiting, limb weakness,
stroke-like episodes, partial paralysis, partial blindness, seizures, migraine-like
headaches, diabetes, short stature, heart problems and kidney problems.
 Maternally Inherited Diabetes and Deafness (MIDD) - The hearing loss is
sensorineural. The only other finding is diabetes.
 Kearns-Sayre Syndrome (KSS) - The hearing loss is sensorineural. Other
findings include: unsteady gait (ataxia), short stature, delayed puberty,
progressive paralysis of the eye muscles (ophthalmoplegia) and progressive
blindness (retinopathy).
 Myoclonic Epilepsy and Ragged Red Fibers (MERRF) - The hearing loss is
sensorineural. Other findings include unsteady gait (ataxia), epilepsy, and
possible blindness (optic atrophy).
 1555DELG - The hearing loss is sensorineural and may be progressive. Those
who have this condition may have sudden hearing loss when exposed to
aminoglycoside antibiotics (e.g., neomycin, gentamycin, streptomycin,
kanamycin, tobramycin, or amikacin).

In 70% of cases of genetic hearing loss, the cause is autosomal recessive; therefore,

 Both parents are "carriers" of a gene that causes recessive hearing loss.
 There are many different genes in many different locations that may cause genetic
hearing loss. At one of these locations, a parent my carry one of the recessive genes
that can cause deafness and one of the dominant genes that is responsible for normal
hearing. Because each parent has only one recessive gene that can cause hearing loss,
both parents can hear.
 If each parent passed on one recessive gene, then the child would receive two
recessive genes (one from each parent) and that is the cause of the recessive hearing
loss.

In 15% of cases of genetic hearing loss the cause is autosomal

dominant.

 In this case only one parent may have the dominant gene for
hearing loss. That parent will have some degree of hearing
loss. If the autosomal dominant gene also has other physical
findings (i.e., it is syndromic), the parent who has the
dominant gene also may have some of these other physical
findings.
 The parent with the dominant gene may pass that gene for hearing loss on to the child.

For the final and remaining 15% of genetic hearing loss cases, the answer to the question,
"Why did this happen to my child?" is specific to the particular type of genetic inheritance.
Why is my child being referred for Genetic Testing?
Genetic testing may determine whether your child's hearing loss is due to non-genetic causes
or to a gene that causes hearing loss. From this information, professionals can calculate the
likelihood that other children in your family may also have a hearing loss due to the same
cause. A full genetic evaluation will also determine if there are other health conditions that
also need to be addressed.

What does this mean for my child?

In general, why your child has a hearing loss does not affect how
your child will be educated. Management of your child's hearing
loss will be based upon the specific characteristics of your child and
his or her communication needs. The findings from a genetic
evaluation may be relevant for your child's medical care

What is the likelihood that this will happen again with any
other children in my family?
If the cause of your child's hearing loss is an autosomal recessive
gene, then the likelihood that this will happen in another child (assuming the same partner) is
1 in 4 (25%).

If the cause of your child's hearing loss is an autosomal dominant gene, then the likelihood
that this will happen in another child (assuming the same partner) is 1 in 2 (50%).

Should I have my other children tested?

If it is determined that you and your partner carry the silent (recessive) gene which causes a
hearing loss, then each of the children resulting with that partner have a 2 in 3 (66%) chance
of also carrying that same gene.

Whether or not your hearing children should be tested to determine if they also carry the
deafness gene is a matter of choice. Your hearing children may want to know their own gene
carrier status so they would know whether to have their partners tested to determine if their
children (your grandchildren) have a chance of having hearing loss due to this gene.

There is a 2 in 3 chance that hearing siblings (brothers and sisters)

of a child with recessive hearing loss carry the hearing loss gene
(like you and your partner). If this is the case, then their life partner
could be tested to determine if they are also a carrier. If that partner
is also a carrier of the same gene, then each of their children would
have a 1 in 4 (25%) chance of having the same genetic hearing loss.
If that partner does not carry the same gene, then all of their
children would be hearing, although each child would have a 50%
chance of carrying the hearing loss gene.

There is a 1 in 3 chance that hearing siblings do not carry the recessive hearing loss gene. If
this is the case, there is virtually no chance of having a child with a hearing loss due to this
gene, as the gene is not passed on.

Is this something that I need to be concerned about in my other relatives?

If you and your partner carry a recessive gene, then at least one of your parents and one of
your partner's parents also carry the gene. This means that each of your brothers and sisters
has a 1 in 2 (50%) chance of carrying the same gene.