genetic screening for deafness

Genetic screening for deafness

Richard J.H. Smith, MD, FACS, FAAPa,*,Stephen Hone, MB, FRCSI(ORL)b

aDepartment of Otolaryngology, Molecular Otolaryngology Research Labs, University of Iowa,

200 Hawkins Drive, Iowa City, IA 52242, USAbPediatric Otolaryngology/HNS, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA

Our understanding of the genetics of hearing impairment has advanced rapidly

over the past decade. Several genes that are essential for normal hearing have

been cloned, and numerous others have been localized to specific chromosomal

regions. As this basic science knowledge is translated from the laboratory bench

to the patient’s bedside, it is changing the medical evaluation of hearing im-

pairment. The focus of this article is to define these changes by explaining the

role of genetics and genetic testing in the evaluation of deaf persons.

Epidemiology

Developed countries have seen an increase in the relative incidence of hered-

itary childhood deafness because major causes of acquired prelingual deafness

have been eliminated through improved neonatal care and universal immunization

programs. For example, as a result of the vaccination program for congenital

rubella, this major cause of acquired congenital deafness in the 1960s is now

exceedingly uncommon; more recently, the vaccination program for Haemophilus

influenzae type B has decreased the incidence of deafness from meningitis.

Although current prevalence estimates of prelingual deafness vary, figures

based on universal neonatal screening programs are probably the most accurate.

In the United States, estimates from these programs place the rate of bilateral

hearing loss greater than 35 dB at 1.4 to 3 per 1000 [1–3]; European rates, ob-

tained mainly from retrospective studies, are similar with ranges from 1.4 to 2.1

0031-3955/03/$ – see front matter D 2003, Elsevier Inc. All rights reserved.

doi:10.1016/S0031-3955(03)00026-9

This article was supported, in part, by grants RO1-DC02842 and RO1-DC03544 from the National

Institute for Deafness and Other Communication Disorders.

* Corresponding author.

E-mail address: [email protected] (R.J.H. Smith).

Pediatr Clin N Am 50 (2003) 315–329

per 1000 [4–6]. In more than half of these cases the deafness is inherited as the

only trait (nonsyndromic) in a simple Mendelian recessive fashion (75%–80% of

cases), with fractional autosomal dominant (� 20%), X-linked (2%–5%), and

mitochondrial (� 1%) contributions [5–8].

Although systematic studies to determine the frequency and mode of inheri-

tance in postlingual deafness are not available, many families segregating deafness

have been described, and in nearly all the pattern of inheritance was autosomal

dominant. These observations suggest that the majority of families with hereditary

deafness fall into two categories: those segregating recessive prelingual deafness

and those segregating dominant postlingual progressive deafness.

Recessive prelingual deafness

In 1994, Guilford et al [9] mapped the first autosomal recessive nonsyndromic

deafness (ARNSD) locus, DFNB1 (DFN, deafness; B, recessive; integer, loci in

order of discovery) to chromosome 13q12. Three years later, the DFNB1 gene

was identified as GJB2 [10]. Surprisingly, although 33 loci have now been

localized and alleles variants of more than 15 genes have been related causally to

ARNSD, mutations in GJB2 account for approximately half of hereditary

deafness in most developed countries, including the United States, many

European countries, Israel, and Australia. GJB2-related deafness also has been

repeatedly described in several Asian, Latin American, and African countries, but

it appears to be less frequent in these regions.

Mutations in GJB2 cause deafness by altering the function of the encoded

protein connexin 26 (Cx26) within the inner ear. Cx26 aggregates in groups of six

around a central 2.3-nm pore to form a toruslike structure called a connexon.

Connexons from neighboring cells covalently bond to form intercellular chan-

nels. Aggregations of these connexins are called plaques and are the constituents

of gap junctions. Although the definitive function of Cx26 in the inner ear is not

known, connexon channels allow for transmission of small ions such as

potassium and calcium, and signaling molecules including cAMP and inositol

triphosphate [11]. In the cochlea, Cx26 is expressed in the epithelial cell gap

junction system and the connective tissue cell gap junction system. Presumably,

these systems are involved in potassium circulation, allowing potassium that

enters hair cells during sound mechanosensory transduction to be recycled to the

stria vascularis [12]. Mutations in GJB2 affect the function of Cx26 and are

believed to cause aberrancies in potassium recirculation, subsequently leading to

cell death and deafness [13].

GJB2 and deafness

Mutations causing GJB2-related deafness have been identified in 35% of

sequential individuals referred for hearing loss or cochlear implantation in the

United States [14]. The most common deafness-causing allele variants of GJB2 in

R.J.H. Smith, S. Hone / Pediatr Clin N Am 50 (2003) 315–329316

the Midwest United States are the frameshift deletions 35delG and 167delT, the

missense mutation V37I, and the large deletions del342kB (delGJB6-D13S1830)

and 313del14 (Tables 1, 2). There are marked variations in the frequencies of

these mutations, however, that are ethnic specific. For example, although the

35delG mutation is most common in persons of northern European descent,

167delT is most common among Ashkenazi Jews [15] and 235delC is most

common among Asians [16]. Carrier rates for these mutations in hearing persons

vary accordingly and have been reported to be 2.5% for the 35delG mutation in

the Midwest United States, 4% for the 167delT in the Ashkenazi population, and

1% for the 235delG among Asians.

The DFNB1 phenotype

All individuals with GJB2-related deafness have sensorineural hearing loss.

Usually, the deafness is profound (> 90 dB; 50% of cases) or severe (71–90 dB;

30% of cases), although moderately severe (56–70 dB) or moderate (40–55 dB)

deafness also is common (20% of cases). A small fraction of persons (< 2%) have

only a mild hearing loss (< 40 dB) [14,17–20]. This degree of variability occurs

even among individuals with the same mutations. The amount of residual hearing

Table 1

Relative frequency of allele variants in persons with GJB2-related deafness

Allele variant Percentage

35delG 68.70%

167delT 6.87%

V37I 3.05%

del342kBa 1.91%

313del14 1.53%

V84L 1.15%

R184P 1.15%

R143W 1.15%

50 donor SSb 1.15%

a delGJB6-D13S1830.b splice donor mutation, IVS1 + 1G>A.

Table 2

Common genotypes in persons with GJB2-related deafness

Genotype Percentage

35delG-35delG 52.67%

35delG-167delT 7.63%

35delG-del342kBa 3.05%

167delT-167delT 2.29%

V37I-V37I 2.29%

35delG-269insT 1.53%

35delG-313dell4 1.53%

35delG-50 donor SSb 1.53%

a delGJB6-D13S1830.b splice donor mutation, IVS1 + 1G>A.

R.J.H. Smith, S. Hone / Pediatr Clin N Am 50 (2003) 315–329 317

in GJB2-related deafness is highly heritable, however; individuals from the same

family tend to have similar levels of hearing, but can differ in the degree of

residual hearing. Although it is presumed that the deafness in all individuals with

GJB2-related deafness is congenital, two neonates homozygous for the 35delG

mutation have been identified who passed neonatal screening tests and sub-

sequently developed profound deafness [21]. Whether this type of rapid hearing

loss is a frequent occurrence in the first year of life in individuals with GJB2-

related deafness is not known.

The typical audiogram has a downsloping (two thirds of cases) or flat (one

third of cases) pattern, although Mueller et al [19] found that 4 out of 31 persons

with GJB2-related deafness had ‘‘U-shaped’’ audiograms. Estivill et al [22] also

reported U-shaped audiograms among several profoundly deaf individuals, with

hearing levels at 100 dB for the high and low frequencies in comparison with

120 dB for the midfrequencies. Selective low-frequency hearing loss has not been

identified in Cx26 deafness. The degree of symmetry between ears is usually

high, with differences between ears (< 20 dB) noted in less than one fourth of

individuals [17,18]. A single case of unilateral mild hearing loss has been

reported in one individual with atypical mutations [23].

Neither improvement nor fluctuation in hearing levels has been noted over the

long term in GJB2-related deafness, and progression appears to be slow or

nonexistent. Mueller et al [19] reported a 5-dB to 15-dB decrease in hearing in

the better hearing ear in three individuals over at least 4 years and a less than 5-dB

decrease in three individuals. Five out of ten individuals studied over at least

6 years by Cohn et al [17] had progression, ranging from 15 to 31dB. In contrast,

none of the 12 individuals studied by Wilcox et al [24] showed progression, and

only 2 out of 16 children studied over a 10-year period by Denoyelle et al [18]

showed progression.

The stability of Cx26 deafness is reliable enough to have clinical implications.

Except for highly unusual cases, individuals with this type of deafness do not

require more than annual audiologic follow-up to ensure the stability of their

hearing. The lack of fluctuation also may aid in determining candidacy for

cochlear implantation. Among individuals with high levels of residual hearing,

brain stem auditory evoked responses are consistent with the degree of deafness.

In contrast, distortion product otoacoustic emissions are suppressed out of

proportion to the degree of deafness, and may be suppressed among normal-

hearing carriers of GJB2 deafness-causing allele variants [15,25].

Family history of deafness

Because GJB2-related deafness is recessive, in most affected individuals there

is no family history of deafness. Due to the high population carrier rate of GJB2

deafness-causing allele variants, an increased incidence of deafness among

nonsibling relatives and pseudodominant inheritance patterns may be seen. The

latter occurs when a deaf individual marries a carrier and has a deaf child. True

dominant GJB2-related deafness (DFNA3) is rare, but has been identified in

families with three unique mutations: R184Q, W44C, and C202F [26–28].


GJB2-related deafness and temporal bone anatomy

In general, GJB2-related deafness is not associated with bony abnormalities of

the cochlea. Normal CT has been reported in 42 individuals with GJB2-related

deafness examined by Cohn et al [17] and Denoyelle et al [18]. In contrast,

Kenna et al [23] found bony overgrowth at the time of surgery and asymmetry of

the right modiolus, each in one patient.

Vestibular function

All persons with GJB2-related deafness studied have had normal vestibular

function and developmental motor milestones with the exception of two

individuals—one person had vertigo and migraine accompanied by unilateral

weakness and the second, a premature baby, had maturational vestibular weak-

ness [17,18].

Comorbidity

GJB2-related deafness is not associated with known medical abnormalities.

Specific rare mutations in GJB2 are associated with deafness and skin abnor-

malities, including the Vohwinkle’s syndrome type of keratoderma (D66H),

diffuse hyperkeratosis (R75W), and palmoplantar keratoderma (G59A and

delE42) [29]. Tests of vision, intelligence, electrocardiography, and thyroid

function, however, are normal [14,17,30,31].

Cochlear implantation

In children with GJB2-related deafness, cognitive dysfunction is not reported

and neural structures are preserved, two findings that predict excellent cochlear

implantation candidacy. This prediction has been verified—children with GJB2-

related deafness exhibit the type of gains experienced by most children with

congenital deafness after cochlear implantation, and, more importantly, they

predictably demonstrate excellent results [30,31].

GJB2 mutation screening

The genetic diagnosis of GJB2-related deafness is dependent on identifying

mutations within the DNA of affected individuals. DNA may be extracted from

any nucleated tissue, although peripheral whole blood (approximately 10 cm3)

most commonly is used. Mutation screening of the extracted DNA can be

completed using a variety of techniques. The most common mutation (ie, 35delG)

may be identified through an allele-specific polymerase chain reaction assay or

other techniques that identify specific DNA sequence variations. These mutation-

specific techniques are known collectively as mutation identification strategies

and suffer the weakness of failing to identify other allele variants. Additional

general techniques for mutation screening include single-strand conformational

polymorphism analysis, heteroduplex analysis, and denaturing high performance

liquid chromatography (DHPLC) analysis. Bidirectional sequencing of DNA

strands is the gold standard against which these other methods must be measured.


If only a single deafness-causing allele variant of GJB2 is identified, additional

screening must be completed. In some cases, ambiguous data are generated,

making it impossible to establish a definitive genetic diagnosis.

SLC26A4 and deafness

In 1896, Vaughan Pendred [32], a British physician, described an Irish family

in which two out of 10 children were congenitally deaf and had goiters. This

condition, now known as Pendred syndrome (PS), is estimated to account for 1%

to 8% of congenital deafness.

The PS phenotype

The hearing loss in PS is typically bilateral, prelingual, more severe in the high

frequencies, and associated with specific cochlear malformations. Hvidberg-

Hansen et al [33] provided the first description of the temporal bone histopathol-

ogy in their study of a single patient who had dilation of the endolymphatic duct

and sac, enlargement of the vestibular aqueduct, and cochlear dysplasia. In a

premorbid assessment of 17 affected persons using axial pyramidal tomography,

Johnsen et al [34] found Mondini dysplasia (the presence of both an abnormal

cochlea and a dilated vestibular aqueduct) in all cases. This anomaly is not an

invariable finding, however, as documented in a study by Andersen [35], in

which Mondini dysplasia was found in only 8 out of 13 affected persons. With

the improved resolution of CT and MRI, Phelps et al [36] found bilateral dilated

vestibular aqueducts (DVAs) in 31 out of 40 affected persons, and Mondini

dysplasia in 8 persons. Based on these data, a temporal bone assessment should

be included in the diagnostic evaluation of PS.

The goitrous changes of the thyroid usually do not present until puberty.

Morgans et al [37] have shown that the thyroid abnormality is due to abnormal

iodide processing demonstrable with the perchlorate discharge test. In this test,

individuals are given radiolabeled iodine. Potassium perchlorate, a competitive

inhibitor of iodide transport into the thyroid, also is administered. In normal

individuals, the amount of iodide in the thyroid remains stable, reflecting the

rapid oxidation of iodide to iodine and its incorporation into thyroglobulin. In

persons with PS, however, incorporation is delayed and as iodide leaks back into

the bloodstream, the amount of radiolabeled iodine in the thyroid decreases by

more than 10%. To determine the course of thyroid disease, Friis et al [38]

studied 17 affected persons and found that 8 remained euthyroid. Of the 9 who

became hypothyroid, 4 previously had undergone thyroidectomy. Reardon et al

[39] studied 43 affected persons with goitrous changes and showed that 24 were

euthyroid and 19 were hypothyroid. Thus, in the majority of cases, persons with

PS remain euthyroid.

Phenotypic heterogeneity has made it difficult to reach a consensus on the

best screening strategy to diagnose PS. For example, in a two-sibling family

described by Johnsen et al [34], one sibling demonstrated the classic features of

PS—severe-to-profound sensorineural hearing loss (SNHL), goiter, and a pos-


itive perchlorate discharge test—but the other sibling had only mild sensorineural

deafness and no goiter. Reardon et al [39] found goiter in 83% of people with a

positive perchlorate discharge test, but found that thyroid manifestations and the

degree of hearing loss could vary between individuals in a family. Furthermore,

the perchlorate discharge test is not consistently positive, as illustrated by a study

[40] in which only three out of six individuals with confirmed PS had greater

than 10% iodide washout. In addition, Reardon et al [39] reported a 2.9% false-

negative rate for this test. Therefore, there is no single sign or clinical test that

can unambiguously identify PS.

The genetics of PS

In 1996, PS was mapped to a 9-cm region on the long arm of chromosome 7

(7q21–34) [41]. Other groups [42–45] confirmed this linkage result and, with

fine mapping, the candidate interval was reduced to 0.8 cm. In 1997, 100 years

after the disease was first recognized, Everett et al [46] cloned the causative gene

and named it PDS. To date, 62 mutations have been found in a total of 116 fam-

ilies [47]. Most of these mutations have been reported in single families;

however, 15 mutations have been reported in more than one family and four

(L236P, IVS8 + 1G > A, T416P, and H723R) accounted for approximately 60%

of the total PS genetic load [48]. A form of nonsyndromic deafness, DFNB4

(characterized by sensorineural deafness and DVA) localizes to the same genomic

region and is allelic to PS. As is implied by the nomenclature, persons with

DFNB4 do not have thyroid anomalies. In 1998, Li et al [49] demonstrated two

mutations in PDS in a consanguineous Indian family with DFNB4. Usami et al

[50] also demonstrated seven mutations in six families with DFNB4.

Functional studies by Scott et al [51] suggest that the observed phenotype may

correlate with the degree of residual function of the encoded protein pendrin.

Mutations that result in no residual transport function appear to be associated

with the PS phenotype; minimal transport ability prevents thyroid dysfunction,

but sensorineural deafness and temporal bone anomalies still occur and affected

persons have DFNB4. Based on similarities to other solute carrier proteins, PDS

has been renamed SLC26A4. This gene is now known to be the major genetic

cause of PS and DFNB4.

PS patient care

In 2001, Campbell et al [48] studied genotype–phenotype correlations in

relation to temporal bone abnormalities. The group found mutations in SLC26A4

in 82% of multiplex families with DVA or Mondini dysplasia, but in only 30% of

simplex families—results suggesting that mutations in SLC26A4 are the major

genetic cause of DVA or Mondini dysplasia. Reardon et al [39] have advocated

for genetic testing to establish a diagnosis of PS, because variability in onset and

severity of goiter is an unreliable clinical indicator of disease. The perchlorate test

also is unreliable, as illustrated in two consanguineous Tunisian families with a

genetic diagnosis of PS in which 11 out of 23 affected individuals with goiter and

mutations in SLC26A4 had negative perchlorate washouts [52]. These results,


coupled with the data reported by Campbell et al [48] in which patients were

ascertained based on temporal bone findings, make mutation screening of

SLC26A4 the most reasonable diagnostic test in individuals with sensorineural

deafness and cochlear malformations (DVA or Mondini). Although a positive

result currently does not impact habilitation, it does permit a definitive diagnosis

and makes accurate genetic counseling possible.

Dominant progressive deafness

At this time, genetic testing of small families segregating autosomal dominant

nonsyndromic deafness (ADNSD) is difficult for two reasons. First, there are

more than 40 loci currently known to be associated with ADNSD with no single

locus making a substantial relative contribution to the total ADNSD genetic load.

This fact means that genetic testing requires mutation screening of numerous

genes, a labor-intensive process. Any identified nucleotide changes then must be

studied to determine whether they affect protein function—in most cases, a

definitive diagnosis will be impossible to make. The second limitation reflects the

general inability to correlate genotype with audiologic phenotype. This limitation

means that it is not possible to identify a particular gene for mutation screening

based on the audiogram. There is, however, one notable exception.

DFNA6/14

DFNA6 and DFNA14 were originally mapped to nonoverlapping, adjacent

regions on chromosome 4p16; however, a subsequent study indicated that these

loci are allelic. The DFNA6/14 hearing loss is caused by allele variants of WFS1,

a gene predicted to encode an 890 amino acid transmembrane protein with nine

helical transmembrane segments.

The DFNA6/14 phenotype

Persons with DFNA6/14 have a moderate, bilateral, symmetrical hearing loss

below 4000 Hz. In the high frequencies, their hearing is often normal [53,54].

This type of low-frequency hearing loss also is a characteristic of DFNA1; with

DFNA1, however, there is rapid progression and ultimately a profound loss

across all frequencies. DFNA6/14, in contrast, shows no or only mild progres-

sion, although in some families, age-related hearing loss in the high frequencies

eventually results in a flat audiogram with a moderate hearing loss [55].

In evaluating families segregating presumed ADNSD it is very useful to

construct a pedigree and an audioprofile. The latter is a composite audiogram that

shows on a single graph the audiograms of several family members averaged

decade by decade. If the audioprofile shows preservation of low-frequency

hearing in a family segregating ADNSD, mutation screening of WFS is war-

ranted. In approximately 85% of families meeting these criteria, WFS1 mutations

will be found (Fig. 1) [56].


Hearing loss and WFS1

Mutations in WFS1 are associated with Wolfram syndrome (WS) and

DFNA6/14. WS shows an autosomal-recessive inheritance pattern and also is

known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and

deafness). The minimal diagnostic criteria are diabetes mellitus and optic atrophy

[57], although additional symptoms include sensorineural deafness, ataxia,

peripheral neuropathy, urinary tract atony, and psychiatric illness [58,59].

Remarkably, the hearing impairment in WS patients affects the high frequencies

[60,61]. According to the Human Gene Mutation Database, 65% of WS

mutations are inactivating, suggesting that loss of function of WFS1 is the cause

of the DIDMOAD phenotype [62]. In contrast, no inactivating mutations have

been found in DFNA6/14, indicating that specific mutations that do not disrupt

the complete protein are responsible for the low-frequency hearing loss pheno-

type [56].

The majority of frameshift and nonsense mutations that have been identified in

WS patients are localized to predicted transmembrane domains [63]. With the

exception of the K193Q mutation, which is located in the first extracellular

domain, all mutations identified in families segregating DFNA6/14 are located in

the fifth intracellular domain [56]. This finding suggests that mutations in this

domain affect a limited number of functions and that this domain plays an

important role in the function of the inner ear.

Fig. 1. Audioprofile of DFNA6/14 deafness. This composite audiogram shows the decade-by-decade

change in average auditory function that is typical for DFNA6/14 deafness. Hearing in the low

frequencies is preserved. In families showing this type of profile, mutation screening of WFS

is warranted. (Courtesy of Patrick L.M. Huygen, PhD.)


Genetic testing

Its perceived value

Although genetic testing can be offered to deaf and hard-of-hearing persons

and their families, it is useful to ask whether this service is perceived as valuable.

This question is not trivial, because deafness differs from most conditions for

which genetic testing is available. Testing for genetically determined cancer, for

example, may permit an at-risk individual to make lifestyle changes or pursue

screening protocols to prevent disease or limit its impact. Many persons,

however, consider deafness neither a disease nor a handicap. For example,

members of the deaf community embrace their deafness as an integral part of

their identity, shared history, and social customs [64]. They historically have

espoused a negative attitude toward the medical community, which they perceive

as a threat to their culture [65]. This negative attitude extends to genetics and

genetic research on deafness, as documented by a recent survey of members of

the deaf community who showed a predominantly negative attitude toward the

use of genetic testing for deafness [66]. Most deaf individuals believe that genetic

testing does more harm than good and remain concerned about the implications

and ramifications of future discoveries in genetics.

Although these data are helpful in understanding the perspectives of this

community, they cannot be generalized to individuals who do not consider

themselves ‘‘culturally’’ deaf. Most hearing parents who unexpectedly have a

deaf child perceive deafness as a disability and turn to medical specialists for

assistance. These parents do not know how to relate to their child, and do not

know how their child will be able to relate to the ‘‘hearing’’ world. Their initial

reaction to a diagnosis of deafness is similar to the reaction expressed by parents

who have a child with multiple congenital malformations. There is a sense of

shock, denial, disbelief, grief, pain, helplessness, guilt, and depression—feelings

that reflect the sense of loss associated with the hopes and dreams that parents

may have had for their child’s future. Often, parents blame themselves for their

child’s perceived ‘‘handicap’’ and desperately search for an explanation for the

condition. Not infrequently, parents conclude that the cause was due to their own

ignorance, neglect, or misfortune during or after the pregnancy. By providing

these parents with a specific etiology of deafness, more accurate information can

be provided, which can alleviate incorrect or inaccurate beliefs [67].

Genetic counseling

Because 90% to 95% of deaf children are born to normal hearing parents,

understanding the attitudes of this group (ie, normal-hearing parents of deaf

children) is necessary for optimal counseling strategies [68]. In a study that

addressed these issues, Brunger et al [69] surveyed 96 normal-hearing parents of

deaf children and found that the vast majority (96%) approve of genetic testing

for deafness and believe that it should be offered prenatally (87%). Although


answers to several questions, however, clearly verified that normal-hearing

parents of deaf children have an overall positive attitude toward genetic testing

for deafness, their understanding of genetics is poor.

Most normal-hearing parents of deaf children (>90%) have inaccurate beliefs

about their own and their child’s recurrence chances. Remarkably, there was no

difference between parents who had had genetic testing for their children and

those who had not had such testing. In fact, some parents (32%, or 6 out of 19)

who received negative GJB2 test results believed that their child did not have

‘‘the gene’’ that causes deafness. These individuals did not understand that

deafness is heterogeneous and mistakenly thought that their recurrence chance for

having another deaf child was 0%. Clearly the majority of parents either did not

receive genetic counseling or received counseling that was inadequate.

Such inaccuracies provide a clear example of why formal pretest and posttest

genetic counseling is important. If normal-hearing parents of deaf children are

provided appropriate and accurate information, they can make informed decisions

about genetic testing for deafness. Formal counseling also ensures that those who

receive genetic test results have a clear understanding of their meaning, including

how recurrence chances are changed. These benefits have been verified in

families who received counseling for other genetic conditions [70].

Summary

Genetic testing for deafness has become a reality. It has changed the paradigm

for evaluating deaf and hard-of-hearing persons and will be used by physicians

for diagnostic purposes and as a basis for treatment and management options.

Although mutation screening is currently available for only a limited number of

genes, in these specific instances, diagnosis, carrier detection, and reproductive

risk counseling can be provided. In the coming years there will be an expansion

of the role of genetic testing and counseling will not be limited to reproductive

issues. Treatment and management decisions will be made based on specific

genetic diagnoses.

Although genetic testing may be a confusing service for the practicing

otolaryngologist, it is an important part of medical care. New discoveries and

technologies will expand and increase the complexity of genetic testing options

and it will become the responsibility of otolaryngologists to familiarize them-

selves with current discoveries and accepted protocols for genetic testing.

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