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
- 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)
-  Morton CC, Nance WE., Newborn hearing screening–a silent revolution. N Engl J Med. 2006 May 18; 354(20):2151-64.
-  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.
-  Cryns K, Van Camp G, Deafness genes and their diagnostic applications. Audiol Neurootol. 2004 Jan-Feb; 9(1):2-22.
-  Toriello HV, Reardon W, Gorlin RJ. Hereditary Hearing Loss and its Syndromes. Oxford University Press, Inc; Oxford: 2004.
What are the common Genetic ENT Disorders?
- 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
- 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 (3-5ml in EDTA tubes)
- 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)
FREE GENETIC COUNSELING
Actia offers all your patients FREE 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
- Latest technologies
- Helpful customer service
- Clear result interpretation
- Counselling sessions with our genetic counsellors