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422 Disorders of the Auditory System
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environment). In these cases, individuals
may inherit a predisposition to develop a
disorder, but the disorder does not necessarily manifest itself if the individual is
not exposed to the environmental conditions that will trigger the response. Genes
and environmental factors may also cause
a disorder in an additive fashion.
An inheritance pattern can also be
digenic. In these cases, mutations in two
genes interact to cause deafness or hearing loss. In a few cases of inherited hearing loss, there are modifier genes that may
determine if a genetic mutation will lead
to a condition or disorder or not. Modifier
genes interact with other genes in a variety of ways. As discussed by Welch (2006),
one gene may determine if a person has
hearing loss (or not), and a second gene
may determine the degree of hearing loss
experienced (mild versus profound, etc.).
It is also possible that a gene may determine the presence or absence of a hearing
loss, and an allele at a modifier locus may
“save” the individual with the genotype
from experiencing hearing loss. In this
case, the individual presents phenotypically with normal hearing.
the genetics of
heaRing loss
In humans, hearing loss is the most common sensory deficit. The prevalence of
congenital hearing loss in newborns is
about 2 to 3 per 1,000 (National Institute
on Deafness and Other Communication
Disorders, 2016). The overall prevalence
of hearing loss increases dramatically
with age due to the significant increase in
the number of individuals with acquired
hearing loss in older populations. It is estimated that 1 in 3 people between the ages
of 65 and 74 years of age have hearing
loss, and nearly half of those over the age
of 75 years have hearing loss (National
Institute on Deafness and Other Communication Disorders, 2018).
This increase in the prevalence of
hearing loss in adults compared to children is due in part to the fact that genetic,
medical/health, and environmental factors contribute to the development of
hearing loss in many individuals, and in
many cases, there are interactions among
these factors (e.g., many individuals
inherit a gene that increases their susceptibility to the damaging effects of noise
exposure). Genetic etiologies account for
the majority of hearing losses diagnosed
in infancy (often detected by newborn
hearing screening) or in very early childhood, with fewer hearing losses in this
population attributed to environmental
influences such as infections (i.e., cytomegalovirus), prematurity, ototoxicity, and
so forth (Kochar, Hildebrand, & Smith,
2007). Genetic etiologies also contribute to
a significant proportion of hearing losses
of later onset (Kochhar et
ever, it is difficult to estimate the prevalence of genetic etiologies in age-related
hearing loss due to the frequent presence
of other comorbidities in older adults and
the elderly, coupled with the fact that
genetic testing is far less common among
older individuals with hearing loss. In a
recent publication, Shearer et al. (2017) provided estimates of the percentages of
genetic and nongenetically based pediatric
hearing losses. These authors estimated
that 1 in 500 prelingual children in developed countries have hearing loss, with 80%
of these losses being related to genetic
causes and the remaining 20% being related to acquired conditions and/or environmental causes. Clearly, genetic etiologies
play a major role in congenital hearing loss.
al., 2007). How-
9. Hereditary and Congenital Hearing Loss 423
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Genetic hearing losses (as well as
hearing losses in general) are often classified by type and onset of the hearing loss.
These classifications (described in detail
in Chapter 3) include the following types
of hearing loss: conductive, sensorineural,
mixed, and central auditory dysfunction.
In addition, the onset of hearing loss is
taken into consideration with respect to
if the hearing loss develops before the
acquisition of speech (prelingual) or after
the development of speech and language
(postlingual). All congenital hearing losses
are prelingual, but not all prelingual hearing losses are congenital. Perhaps the
most common and useful classification of
hereditary hearing loss is nonsyndromic
versus syndromic hearing loss. These
types of genetically based hearing losses
are discussed in the next section.
Syndromic and Nonsyndromic
Hearing Loss
Hearing loss is one of the most common
of the sensory disorders, which affects
individuals of all ages. As will become
evident in the discussion that follows,
genetic factors account for the vast majority of congenital hearing losses. Interestingly, even in hearing loss related to aging
in the elderly population (i.e., age-related
hearing loss), genetics (along with environmental causes in some cases) may
play a role in the development of the
hearing loss (Alford et al., 2014). In fact,
approximately 30 gene mutations have
already been associated with age-related
hearing loss (Griffith & Friedman, 2017).
Genetic hearing losses can be segmented
into two main categories: syndromic and
nonsyndromic. Syndromic hearing loss
involves not only the auditory system but
also other systems, making it a multifac-
eted disorder. Nonsyndromic hearing loss
involves primarily the auditory system;
however, in some situations, more than
the auditory system can be involved but
not nearly to the degree as is observed in
syndromic hearing loss.
Nonsyndromic Hearing Loss
According to Shearer and colleagues
(2017), nonsyndromic hearing losses are
much more common in prelingual children than are syndromic hearing losses.
They estimate that approximately 80% of
the genetic hearing losses in this population is nonsyndromic, with syndromic
hearing loss (which will be discussed
later) accounting for about 20% of the
genetically based hearing losses in prelingual children in developed countries
around the world. Nonsyndromic hearing loss can be autosomal dominant or
autosomal recessive, with the recessive
form accounting for around 80% and the
autosomal dominant form accounting for
approximately 19% of all nonsyndromic
hearing losses. Less than 1% of nonsyndromic hearing losses are reported to have
X-linked, mitochondrial, or microRNA
(miRNA) forms of inheritance (see
Shearer et al., 2017). The miRNA pattern
of inheritance, which was not discussed
earlier, refers to a small noncoding RNA
molecule that functions in RNA degradation or translation repression (Whaid,
Shehzad, Khan, & Kim, 2010), and as can
be seen in the statistics presented previously, it is an uncommon etiologic basis
for genetic hearing loss.
Tables 9–1 and 9–2 provide examples of genes associated with autosomal
recessive nonsyndromic hearing loss and
autosomal dominant nonsyndromic hearing loss, respectively. Included in each of
these tables are the functions associated
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Table 9–1. Examples of Genes Associated With Autosomal Recessive Nonsyndromic
Hearing Loss
Locus Name Gene Name Onset of Hearing Loss Function
DFNB1 GJB2 (Connexin 26)
GJB6 (Connexin 30)
GJB3 (Connexin 31)
DFNB2
DFNB3
DFNB21
DFNB36
Table 9–2 .
Hearing Loss
Locus Name Gene Name Onset of Hearing Loss Function
DFNA1
DFNA3
DFNA10
DFNA17
Examples of Genes Associated With Autosomal Dominant Nonsyndromic
MY07A
MY015
TECTA
ESPN
DIAPH1
GJB2
GJB6
EYA4
MYH9
Prelingual Homeostasis
Pre- or Postlingual Cytoskeletal System
Prelingual Cytoskeletal System
Prelingual Extracellular Matrix
Prelingual Cytoskeletal System
Postlingual Cytoskeletal System
Prelingual Homeostasis
Postlingual Transcription Factors
Postlingual Cytoskeletal System
DFNA36
DFNA48
TMC1
MY01A
with each of the genes mentioned. In
addition, the typical onset of the hearing
loss (i.e., either prelingual or postlingual)
associated with these gene mutations
is provided for each of the genes listed
in both of these tables. These tables provide “examples” of gene mutations that
have been associated with a hearing loss,
but they are not intended to be exhaustive listings of all genetic mutations that
can result in hearing loss. The reader is
Postlingual Cytoskeletal System
Postlingual Unknown
referred to Shearer et al. (2017) and Van
Camp and Smith (2019) for additional
information regarding nonsyndromic
and syndromic gene mutations related to
hearing loss.
Genes create proteins that play a
critical role in the development, function,
and dysfunction of structures throughout
the various systems in the body. There
are a variety of genes associated with the
auditory system (Hood & Keats, 2011).
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According to Van Camp and Smith (2019),
75 autosomal recessive genes associated
with nonsyndromic hearing loss have
been identified. Identifying genes is a
challenging process that includes defining
the phenotype, finding families that have
the genotype of interest, and then pursuing detailed family histories. A few of
the better known genes (especially to the
audiology and otology communities) are
MYO7A, MYO15, and MYH9, which are
motor molecules that encode the myosin
protein. Also notable are the GJB2, GJB6,
and GJB3 genes, which are all categorized
as gap junction proteins that encode the
proteins connexin 26, 30, and 31, respectively. The myosin genes are associated
with movement of actin filaments and the
maintenance of the tip-links of hair cells.
These “movement” proteins make one
think of the motile properties of the outer
hair cells and the critical role they play
in hearing. The GJB2 gene was one of the
first genes identified that was associated
with a high percentage of nonsyndromic
hearing loss (autosomal recessive). Since
the time of this discovery, there have been
more than 100 mutations of the GJB2 gene
categorized, with these mutations yielding varying degrees of hearing loss (Wingard & Zhao, 2015). Mutations in the connexin 26 gene are one of the major sources
of hereditary hearing loss. It was once
believed that a disruption in K
+
recycling
was the primary mechanism responsible
for hearing loss associated with mutations
of this gene; however, this has proven to
in fact not be the case (see Wingard &
Zhao, 2015). More recently, mouse models
have demonstrated that hearing loss associated with connexin deficiencies is not
directly related to hair cell degeneration
but rather to cochlear developmental disorders (Chen, Chen, Zhu, Liang, & Zhao,
2014). This differs from late-onset hearing loss that is believed to result from a
reduction of active cochlear amplification
(Zhu et al., 2015). While advances have
been made with respect to our knowledge of the genetic mechanisms underlying congenital and late-onset hearing loss,
significantly more research in this area
is needed.
Mutations of genes such as the ones
that have been mentioned previously
and/or referred to in the tables can result
in hearing loss. Although in some cases
certain mutations can result in severe to
profound hearing loss, a similar mutation may also result in minimal hearing
loss. This kind of variability seems common (Hood & Keats, 2011). Having said
this, some trends in regard to hearing
loss have been reported. First, a very high
percentage of nonsyndromic hearing loss
is sensorineural in nature, as the various
gene mutations discussed previously
affect proteins that influence the structures and functions of the cochlea. There
is also some evidence that gene mutations often yield a certain configuration of
hearing loss, although the degree of loss
may vary. For example, mutations of the
GJB2 gene are known to result in a sensorineural hearing loss. Although the degree of the sensorineural loss can vary from
mild to profound, there is a trend toward
the high frequencies being more involved
than the low and middle frequencies in
individuals with mutations of this particular gene (Shearer et al., 2017). The earlier
discussion has focused on a few of the
more common nonsyndromic genes associated with hereditary hearing loss; however, the reader should be aware that
there are many other genes that also can
result in nonsyndromic hearing loss when
genetic mutations of these genes occur.
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For a more comprehensive listing of these
genes, the reader is encouraged to access
Shearer et
al. (2017).
Syndromic Hearing Loss
More than 400 syndromes with associated
hearing losses have been identified (see
Toriello & Smith, 2013), most of which are
rare. These syndromes can be the result
of chromosomal anomalies, a single gene
mutation, multiple gene mutations, or
a combination of genetic and environmental factors. Most of these syndromes
are inherited in the autosomal dominant
fashion, but some are inherited in autosomal recessive and X-linked transmission patterns (Tables 9–3 and 9–4 provide
information on some common syndromes
along with their modes of transmission,
gene symbols, and clinical findings).
As mentioned previously, 20% of the
genetically based hearing losses in prelingual children from developed countries
around the world are syndromic in nature
(see Shearer et al., 2017), and as such, they
constitute a much smaller proportion of
genetically based hearing losses when
compared to nonsyndromic etiologies in
this population of children.
Pendred Syndrome. Pendred syndrome
is an autosomal recessive disorder with an
unknown incidence. In addition to hearing loss, it is typically associated with a
thyroid condition called a goiter. Exact
prevalence data for Pendred syndrome
are unknown; however, it is estimated
that it accounts for 7% to 8% of all congenital hearing loss (U.S. National Library of
Medicine, 2019e). The hearing loss is sensorineural in nature, and the high frequencies tend to be more involved than the low
frequencies. The hearing loss is progressive, bilateral, and often ranging from
moderate to profound in severity (Smith,
2017). A characteristic of patients with
Pendred syndrome is enlarged vestibular
aqueducts, which cause an enlargement of
the endolymphatic duct and sac (see the
following discussion on vestibular aqueducts). This genetic condition results in a
defect in the ion transportation in endolymphatic fluid resorption, and patients
also have euthyroid goiter. Pendred syndrome often results from a mutation of
the SLC26A4 gene. In addition, the FOXI1
and KCNJ10 genes have also been linked
to this syndrome (Smith, 2017).
Usher Syndrome. Individuals with
Usher syndrome typically present with
sensorineural hearing loss and retinitis
pigmentosa. Usher syndrome has been
reported to have a prevalence rate of 3 to
6 per 100,000 individuals (Saihan, Webster, Luxon, & Bitner-Glindzicz, 2009). It
is believed to account for 50% of the individuals diagnosed with deaf-blindness
(Lentz & Keats, 2016a). Several genes have
been identified for this syndrome (see
Table 9–3). These genes have a role in the
structure and function of the cytoskeleton
of stereocilia of the hair cells. Mutations
in these genes are associated with retinitis
pigmentosa (progressive visual loss and
blindness), vestibular dysfunction, and
ataxia in some cases. Usher syndrome is
classified into 3 types, all of which are
autosomal recessive.
➤ Type I: Onset of retinitis pigmen-
tosa by 10 years of age. Profound
congenital hearing loss and absent
vestibular responses are key characteristics. Pathogenic variants in one of
six genes (MYO7A, USH1C, CDH23,
PCDH15, USH1G, and CIB2) have
been associated with this syndrome
(Lentz & Keats, 2016a).
Retinitis pigmentosa, congenital sensorineural
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hearing loss
Goiter, enlarged vestibular aqueduct,
labyrinthine deformity (i.e., Mondidi dysplasia),
congenital sensorineural hearing loss
Syncopal episodes, prolonged QT interval
on EKG, sudden death, congenital profound
sensorineural hearing loss
Seizures, hypertonia, developmental delays,
ataxia, visual impairment, sensorineural hearing
loss (if biotin not administered)
Retinitis pigmentosa, severe progressive
sensorineural hearing loss
Progressive glomerulonephritis leading to renal
failure, ocular abnormalities (anterior lenticonus
and retinal flecks), progressive sensorineural
hearing loss
Eye disorders (pseudotumor, retinal hyperplasia
or necrosis, and cataracts), mental retardation,
progressive sensorineural hearing loss
Table 9–3. Syndromic Hearing Loss: Examples of Autosomal Recessive and X-linked Genetic Syndromes
Type I: MYO7A, USH1C,
CDH23, PCDH15, USH1G
Type II: ADGRV1, WHRN,
USH2A
(most common)
Syndrome Mode of Transmission Gene Name Clinical Findings
Usher Syndrome Autosomal Recessive
FOXI1, SLC26A4, KCNJ10
Type III: CLRN1, HARS
(second most common)
Pendred Syndrome Autosomal Recessive
KCNE1, KNCQ1
Autosomal Recessive
(third most common)
Jervell and Lange-Nielson
Syndrome
427
BTD
Biotinidase Deficiency Autosomal Recessive
PEX7, PHYH
Refsum Disease Autosomal Recessive
COL4A3, COL4A4, COL4A5
Alport Syndrome X-linked
NDP
Norrie Disease X-linked
Dystopia canthorum, pigmentary abnormalities
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of skin and hair (white forelock), heterochromia
irises, sensorineural hearing loss
Type I: PAX3
Type II: MITF, SNAI2,
SOX10
(most common)
Type IV: EDNRB, EDN3,
Type III: PAX3
Branchial fistulas, cysts or clefts, preauricular
pits, renal malformations, conductive,
sensorineural, or mixed hearing loss
SOX10
EYA1, SIX1, SIX5
Autosomal Dominant
(second most common)
Cleft palate, spondyloepiphyseal dysplasia
leading to osteoarthritis, eye abnormaltiies
(severe myopia and cataracts), progressive
sensorineural hearing loss
Bilateral acoustic tumors (leading to
sensorineural hearing loss), meningiomas,
astrocytomas, ependymomas, juvenile cataracts
Craniofacial deformity (mandibulofacial
dysostosis), malformations in middle and
inner ear structures causing conductive,
sensorineural, or mixed hearing loss
Premature fusion of skull bones and of fingers
and toes, conductive hearing loss
COL2A1, COL11A1,
COL11A2, COL9A1,
COL9A2, COL9A3
NF2
POLR1D, POLR1C, TCOF1
FGFR2
Cranial nerve involvement, sensorineural or
mixed hearing loss
CHD7
Syndrome Mode of Transmission Gene Name Clinical Findings
Table 9–4. Syndromic Hearing Loss: Examples of Autosomal Dominant Genetic Syndromes
Waardenburg Syndrome Autosomal Dominant
Branchiootorenal
Syndrome
Stickler Syndrome Autosomal Dominant
428
Neurfibromatosis Type II Autosomal Dominant
Treacher Collins Syndrome Autosomal Dominant
Apert Syndrome Autosomal Dominant
CHARGE Syndrome Autosomal Dominant
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➤ Type II: Onset of retinitis pigmentosa
in the early 20s. Normal or decreased
vestibular function and mild to
moderate progressive hearing loss.
The hearing loss is characterized by
a mild to moderate low-frequency
hearing loss and a severe to
profound high-frequency hearing
loss. Pathogenic variants are found
in one of the following three genes:
ADGRV1, WHRN (DFNB31), and
USH2A (Lentz & Keats, 2016b).
➤ Type III: Onset of retinitis pigmentosa
at puberty. Progressive hearing loss
and variable vestibular function. This
is typically a result of a pathogenic
variant of CLRN1 gene (Smith &
Jones, 2016).
This syndrome is associated with bilateral cochlear hearing loss that usually
manifests after the presentation of visual
symptoms (visual field cuts and night
blindness). Cataracts can also develop in
individuals with Usher syndrome. Types
I and II account for the majority of Usher
syndrome cases, whereas Type III is much
less common and estimated to account for
only 2% of Usher cases (see U.S. National
Library of Medicine, 2019j).
Apert Syndrome. This syndrome has
an autosomal dominant transmission pattern and has an incidence rate of about 1
in 100,000 cases that is linked to mutations in the FGFR2 gene (Robin, Falk, &
Haldeman-Englert, 2011). Skull and skeletal malformations may include syndactyly (fusion of fingers and toes). A flat
conductive loss is often noted bilaterally,
although sensorineural loss may be present in some cases. A conductive hearing
loss is estimated to occur in 80% of individuals with Apert syndrome. This is typically a result of external auditory canal
stenosis or atresia, middle ear disease,
and/or ossicular abnormalities. There
is also a high rate of semicircular canal
abnormalities (70%) found in affected
individuals (Agochukwu, Solomon, &
Muenke, 2014).
Waardenburg Syndrome. This syndrome
is primarily an autosomal dominant inheritance with four subtypes reported in
the literature. However, in some cases,
an autosomal recessive pattern has been
noted in Types III and IV (National Organization for Rare Disorders, 2015). It is
estimated that Waardenburg syndrome
occurs in about 1 in 40,000 individuals
and accounts for 2% to 5% of congenital
hearing loss (U.S. Library of Medicine,
2019k). Types I and II are the most common forms of Waardenburg syndrome,
while types III and IV are rare. The following summarizes the key features commonly noted in each of the subtypes along
with their associated gene mutations:
➤ Type I: Sensorineural hearing loss;
pigmentary abnormalities of the skin,
hair, and eyes; as well as dystopia
canthorum (lateral displacement of
the inner canthi). Mutations in the
PAX3 gene.
➤ Type II: Similar features to Type I
(sensorineural hearing loss and
pigmentary abnormalities of the skin,
hair, and eyes) with the absence of
dystopia canthorum. Mutations in the
MITF or SNAI2 genes.
➤ Type III: Sensorineural hearing loss;
pigmentary abnormalities of the skin,
hair, and eyes; and upper limb abnormalities. Mutations in the PAX3 gene.
➤ Type IV: Sensorineural hearing loss;
pigmentary abnormalities of the
skin, hair, and eyes; and Hirschprung
disease (an intestinal disorder).
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Mutations in the EDNRB, EDN3, or
SOX10 genes.
While some individuals with Waardenburg syndrome may have normal hearing,
hearing loss can often occur. A hearing loss
exists in 47% to 80% of individuals with
Type I Waardenburg syndrome (Milunsky,
2017). In addition, vestibular dysfunction
has been reported in 75% of individuals
with this particular classification (Hageman, 1977). Type II has a high penetrance
of hearing loss, perhaps as great as 77% to
80% (Milunsky, 2017). Although we were
not able to ascertain the penetrance rates/
percentages of hearing loss in Types III
and IV, it is anticipated that these would
also be quite high as these two types of
Waardenburg syndromes are reported
to represent more severe cases of Types
I and II, respectively. The hearing loss in
Waardenburg syndrome is often congenital, sensorineural, nonprogressive, and
of a moderate to profound degree, and
it presents with a variety of audiometric configurations. Asymmetric hearing
loss as well as normal hearing can occur,
and unilateral or bilateral involvement
is possible. Histopathic findings include
severely defective or even absent organs
of Corti and reduced populations of auditory nerve fibers. Patients typically have
different colored irises and a white forelock. Cleft lip and palate exist in 10% of
the affected individuals, and the severity
of hearing loss may be related to the number of skin and hair pigmentation differences (Reynolds et al., 1995).
Alport Syndrome. Alport syndrome has
an incidence of about 1 per 50,000 live
births (Kashtan, 2019). This syndrome has
an autosomal dominant (5%), an autosomal recessive (15%), and also an X-linked
inheritance pattern (80%) (Hood & Keats,
2011). It is caused by mutations in the
COL4A3, COL4A4, and COL4A5 genes.
There is progressive nephritis with hematuria and proteinuria in the first or second
decade of life. Males are more severely
affected than females in regard to the disease effects. Craniofacial dysostosis, brachiocephaly, bilateral proptosis, saddle
nose, ankylosis, and spina bifida have all
been observed in Alport syndrome. Progressive sensorineural hearing loss and
vestibular hypofunction can exist, and
the hearing loss when present typically
begins as a high-frequency, bilateral sensorineural hearing loss (Kashtan, 2019).
Due to the progressive nature of the hearing loss, it will often extend into other frequencies. The severity of the hearing loss
tends to be greater in men than women.
For autosomal recessive and dominant
forms of Alport syndrome, the age of
onset of the hearing loss is usually in late
childhood or early adolescence with equal
incidence between males and females. In
cases of X-linked inherited mutations, the
hearing loss develops in the majority of
affected males by the age of 40 years (Jais
et al., 2000).
Branchiootorenal Spectrum Disorder.
Branchiootorenal spectrum disorder
(BORSD) syndrome affects about 1 in
40,000 people (Fraser, Sproule, Halel, &
Optiz, 1980; National Organization for
Rare Disorders, 2018). The term “branchio” in the name of this syndrome is
related to the fact that there is maldevelopment of the second branchial arch in
patients with this syndrome. The second
branchial arch contributes to tissue on the
lateral and front of the neck. In order to be
classified as having BORSD, an individual
must present with one of the following
profiles: three major criteria, two major
and two minor criteria, or one major criterion and a first degree relative who has
been diagnosed with BORSD (Chang et
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al., 2004). Major criteria include second
branchial arch anomalies, deafness, preauricular pits, auricular malformations,
and renal anomalies, while minor criteria include anomalies of the external
auditory canals, middle ear, and inner
ear; preauricular tags; and other features
(facial asymmetry, palate abnormalities).
In approximately 90% of the cases, the
syndrome is passed on from one affected
parent to the offspring in an autosomal
dominant inheritance pattern. According
to Stickens and colleagues (2001), more
than 90% of patients with BORSD present with hearing impairment, including
mixed, conductive, and sensorineural
losses. Hearing loss in affected individuals can range from mild to profound and
can be nonprogressive or progressive in
nature (Kemperman et al., 2004). Specific
abnormalities of the external ear include
preauricular pits and tags, lop ear malformations, atresia, or stenosis. There can
be middle ear abnormalities that include
malformation, dislocations, or fixation
of the ossicles, and malformation of the
middle ear space. Inner ear anomalies
can include cochlear hypoplasia and
enlarged cochlear and vestibular aqueducts (Smith, 2018). There are three gene
mutations associated with individuals
with BORSD including EYA1, SIX1, and
SIX5. EYA1 is believed to be the primary
gene mutation and is reported to occur in
approximately 40% of individuals with
BORSD. While both SIX5 and SIX1 have
been found to occur in BORSD, they are
far less common. In some individuals, a
co-existing EYA1 gene mutation has been
identified, and it has been hypothesized
to be the actual underlying cause of the
condition. The proteins produced by these
genes play a critical role in embryologic
development and mutations that occur
are believed to result in abnormal formation of organs and tissues. It should be
noted, however, that there are individuals with BORSD who have none of these
three gene mutations, which suggests
that there is another unidentified gene
(or genes) that can result in this particular
syndrome (U.S. National Library of Medicine, 2019b).
Jervell and Lange-Nielsen Syndrome.
Approximately 1% of infants with profound sensorineural hearing loss may
have Jervell and Lange-Nielsen syndrome
(JLNS), which is an autosomal recessive
disorder (Hood & Keats, 2011; Tranebjærg,
Samson, & Green, 2017). This is primarily a cardiovascular disorder caused by
mutations in one of two genes (KVLQT1
and KCNE1) that are potassium channel genes, which lead to disturbances in
endolymph homeostasis. This syndrome
is characterized by hearing loss and cardiac involvement. The hearing loss typically presents as a profound, congenital
sensorineural hearing loss that is bilateral
in nature. There is elongation of QT intervals on EKGs. These abnormal QT intervals can result in syncopal attacks and
raise the risk of sudden death related to
functional heart disease. Carriers of this
mutation (parents) may have no hearing difficulties but should be screened
for long QT intervals. A family history of
sudden death should encourage consideration of this syndrome. Life expectancy
is severely shortened if the cardiac condition remains untreated.
Treacher Collins Syndrome. Treacher
Collins syndrome has an incidence of
about 1 in 50,000 births (Trainor, Dixon,
& Dixon, 2009). The mode of inheritance
can be either autosomal dominant or
recessive. It is caused by a heterozygous
mutation in the POLR1D or TCOF1 genes
(autosomal dominant) or a biallelic mutation in the POLR1C or POLR1D genes
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