What is ENT Genetics?

Congenital deafness, a highly common birth defect, is seen in as many as 3 in 1,000 babies
Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants
It is also likely that genetics plays an important role in hearing loss in the elderly
Hearing loss and deafness can be due to inherited genetic defects, medical problems, environmental exposure, trauma, and medications

Prevalence

Hearing loss is the most common birth defect and the most prevalent sensorineural disorder
One of every 500 newborns has bilateral permanent sensorineural hearing loss
The prevalence increases to 3.5 per 1000 during adolescence¹
The prevalence of deafness in India is fairly significant and is the second most common cause of disability
The estimated prevalence of adult-onset deafness was found to be 7.6% and childhood-onset deafness was found to be 2%²
Approximately 63 million people (6.3%) in India suffer from significant auditory loss (WHO, 2009a)

[1] Morton CC, Nance WE., Newborn hearing screening–a silent revolution. N Engl J Med. 2006 May 18; 354(20):2151-64.
[2] Denise Yan, Abhiraami Kannan-Sundhari, Subramanian Vishwanath, Jie Qing, Rahul Mittal, Mohan Kameswaran, and Xue Zhong Liu., The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations. Genet Test Mol Biomarkers. 2015 Sep 1; 19(9): 512–527.
[3] Cryns K, Van Camp G, Deafness genes and their diagnostic applications. Audiol Neurootol. 2004 Jan-Feb; 9(1):2-22.
[4] Toriello HV, Reardon W, Gorlin RJ. Hereditary Hearing Loss and its Syndromes. Oxford University Press, Inc; Oxford: 2004.

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What are the common Genetic ENT Disorders?

Non-syndromic

Non-syndromic disorders account for approximately 70% of inherited hearing loss
80% of non-syndromic hearing impairment cases have an autosomal recessive mode of inheritance
20% are caused by autosomal-dominant genes
Less than two percent of cases are caused by X-linked and mitochondrial genetic malfunctions

Syndromic

Hearing impairment is associated with other clinical abnormalities
15% to 30% of hereditary hearing impairments are syndromic
Over 400 syndromes are known to include hearing impairment

Syndromic disorders can further be classified into:

Syndromes due to cytogenetic or chromosomal anomalies
Syndromes transmitted in classical monogenic or Mendelian inheritance
Syndromes due to multi-factorial influences
Syndromes due to a combination of genetic and environmental factors

Why genetic testing for deafness?

Most of the deafness that occurs prelingually has a genetic cause and often inherited in an autosomal recessive manner. Over 80% of these non-syndromic deafness cases are as a result of a mutation in a single gene and are called monogenic
The most commonly mutated gene in deafness patients is GJB2 and the carrier rate in the general population for pathological GJB2 mutation is quite high. About 20% of cases and is most often postlingual and less than 1% of cases, the inheritance occurs through the X-chromosome or the mitochondria³
More than 100 genes are known to cause deafness, either in isolation or as part of a syndrome. About 70% of cases are non-syndromic and are monogenic in nature while the other 30% of cases are syndromic and associated with additional physical findings along with hearing loss in one of the clinical components⁴
Very often clinical symptoms are not always the product of the same genetic variation. Hence, confirmation of a clinical diagnosis through genetic testing which allows to a specific investigation can optimize treatment regimens and such findings help in proper genetic counselling leading to immediate medical/family management
In many cases, genetic testing will clarify the cause of an individual’s deafness, provide information on the likelihood of related health issues, and also establish the risk to other family members and future generations

When do you need to get tested?

In most cases, a genetic test can be performed soon after the onset of clinical symptoms and clinical diagnosis
A genetic test can also be performed even before the onset of the symptoms to identify if an individual is carrying any pathological mutation
Deafness as a disease inherits mostly in recessive fashion and carrier rate is quite high in genes like GJB2. At times genetic testing for a healthy individual is also be advised in view of family history of deafness

Who needs to get tested?

Individuals presenting with the most common symptoms of ENT-related disorders such as hearing loss/impairment
Individuals with a standard preliminary test showing the possibility of hearing loss
Individuals with a positive family history of an ENT disease
Individuals without a positive family history but with symptoms resembling a specific disease indication
Prenatal testing is recommended only in families with affected individuals with prior molecular/genetic testing

Why recommend Actia for patients with genetic ENT disorders?

Actia offers a broad range of pre-designed gene mutation panels which have been developed with an in-depth understanding of the genetic disorder, incorporating the latest research in that particular domain. New updated technologies, helpful customer service, and clear result interpretation along with counselling sessions with our expert genetic counsellors equip us to provide you the best available support for your patients or families with genetic ENT disorders. Actia offers the following gene panel tests

Connexin-26 (GJB2) deletion/duplication analysis
Connexin-26 (GJB2) gene analysis
Deafness gene panel
Mondini defect (SLC26A4) gene analysis
Waardenburg syndrome gene panel

What are the test methodologies?

Next-generation Sequencing (NGS)

Using genomic DNA extracted from blood, the coding regions of all the genes are captured and sequenced simultaneously by NGS technology on an Illumina platform. The sequence data that is generated is aligned and analyzed for sequence variants.

Multiplex Ligation-dependent Probe Amplification (MLPA)

Deletion and duplication analysis of genomic DNA is carried out by MLPA. This method allows for the amplification of multiple targets with only a single primer pair.

Fragment Analysis PCR for Repeat Expansion Analysis:

These rely on the detection of changes in the length of a specific DNA sequence to indicate the presence of repeat expansions.

Test sample requirements

blood test sample Blood (3-5ml in EDTA tubes)

Required forms

Relevant clinical information including all the clinical presentations and symptoms
Test request form

Turn around time (TAT)

21 Working Days for NGS
14 Working Days for MLPA
21 Working Days for Sanger Sequencing
7-14 Working Days for Fragment Analysis
8-15 Working Days for Karyotyping

Extracted DNA samples (1µg high-quality DNA)

GET GENETIC COUNSELING

Actia offers all your patients pre and post-test genetic counselling with our expert and certified genetic counsellors. We provide the best available support for your patients and families via