Hearing loss| Types of deafness |causes and treatment.

 Hearing loss or Deafness

Hearing impairment is defined as, “the inability to perceive sound either partially or completely”.  Deafness is common and congenital disease in the US which affect 1 to 3 per 1000 infants at birth while 1 to 6 have milder impairment. However, in Pakistan it is estimated that about 10% of the population is deaf, means from every 1000 individuals 3.5 are effected. Hearing impairment is the world's third chronic disease.  About 250 million peoples suffer from deafness worldwide. Of that more than 4000 new-born children conceived loss of hearing every year and in these children most of them have genetic diseases. Approximately 60% of hearing loss is because of hereditary variables.

       Deafness can be either, congenital deafness which is present at birth due to both environmental and genetic factors, in every 1000 birth 1 is suffering from congenital deafness.  It may be acquired which are not present at birth but appear later due to some sort of abnormalities, disease, infection or injury both in children and adults mostly environmental responsible for acquired deafness. 

Onset Of Deafness

Onset of deafness might be pre-lingual, post-lingual or Presbycusis.

Ø  When hearing loss occur in early infancy or at congenital condition, before the child seek speech and perception skills referred as pre-lingual hearing loss.

Ø   Deafness occur after the acquisition of basic speech, learning and perception skills known as post-lingual deafness.

Ø  Presbycusis is hearing loss associated with age. About 25% individual have 65 year and about 50% have 80 years.

Types OF Deafness

Deafness categorized into five types namely conductive deafness, sensory or neural deafness, mixed deafness, neural deafness and central deafness.

Ø  Conductive deafness, any obstruction or damage when occur to the outer and middle ear causes conductive deafness.

Ø  Sensory deafness or Sensorineural, caused due to deformities in the middle ear like damage or abnormalities to the nerves or cochlea hair.

Ø   Mixed deafness, related to both outer and middle ear deformities.

Ø   Neural deafness related to deformities occur in the vestibule-cochlear nerves (8 cranial nerves) may cause neural deafness.

Ø  Central deafness, when deformities occur in the auditory nerves responsible for conduction in the central nervous system may cause central deafness.

Degree Of Severity

On the basis of degree of severity and gradual decline of hearing capability it is categorized into the four distinct classes ranges from “no impairment to profound” on the basis of threshold frequency measured in decibels.

Degree of severity of hearing loss in decibels

Degree of severity of hearing loss	Hearing threshold in decibels
0 to 25	Normal
26 to 40	Slight or mild
41 to 60	Moderate
61 to 80	Severe
>80	Profound

 Factors

In a particular population two main factors contributes for deafness, Environmental and Genetic.

Environmental Factors

It is estimated that from total 100% about 60% deafness is caused by environmental factors and remaining 40% is due to genetic factors. Many Environmental factors contributes for deafness, for example ototoxic medication, like Aminoglycosides, Aspirin, Nonsteroidal, Bleomycin, and Tetracycline due to their ototoxicity may damage the hair cell and nerves which cause deafness. Due to certain Infectious agent, which may be prenatal, during pregnancy mother acquired certain infection such as CMV Cytomegalovirus and rubella. Which cause congenital hearing defect. Exposure to noise or loud sound to prolong period is another factor for acquired deafness. Ear diseases such as otitis media, birth conditions which i-e low birth weight, severe neonatal jaundice, and presbycusis which is age related hearing impairment all are the environmental factors that may cause deafness in an individual.

Genetic Factors

Genetic factors are also responsible for deafness, about 80% congenital deafness is caused by genetic factors. Over 100 faulty gene have been identified which are associated with deafness. Similarly, genetically determined deafness may be either congenital present at birth, late-onset which is later appear in life, stable that remain same, or it may be progressive that appear worst with the passage of time. On the basis of Genetics   hearing loss categorized into syndromic hearing loss (SHL) and non-syndromic hearing loss (NSHL).

Syndromic Hearing Loss (SH)

It is estimated that about 30% genetic defect is due to syndromic hearing. Many gene identified for SHL like CACNA1D which causes sinoatrial node dysfunction and deafness. 400 syndrome have been identified which are associated with syndromic hearing loss. Several syndromes identified like, Neurofibromatosis 2 (NF2), Jervell and Lange-Nielsen syndrome, Wardenburg syndrome and Branchial-oto-renal syndrome which may have associated with deafness. Their transmission may be autosomal dominant, recessive and X-linked.

Table of genetic syndromes, their related gene and type of deafness.

Genetic syndrome	Gene	Type	Inheritance
Neurofibromatosis 2 (NF2),	NF2	Sensorineural	Autosomal  dominant
Jervell and Lange-Nielsen syndrome	KCNQ1 KCNE1	Sensorineural	Autosomal recessive
Wardenburg syndrome	WS-I/(PAX3)     WS-II/ (MITF) WS-III/(PAX3) WS-IV/ (EDN3orEDNRB)	Sensorineural	Autosomal dominant
Pendred syndrome	SLC246	sensorineural	Autosomal recessive
Alport Syndrome	COL4A5	sensorineural	X-linked

 Non-Syndromic Hearing Loss (NSHL)

It is investigated that about 70% deafness is due to non-syndromic hearing loss. Approximately 120 gene loci have been known associated with NSHL, which are involve in of ear structure and function development. It is further classified into X linked, autosomal dominant, autosomal recessive, and mitochondrial deafness.

Mitochondrial hearing loss

Mitochondria, contribute 0.5% to 1% in ratio from total hearing impairment. Mitochondrial deafness is maternally inherited and effect both gender equally, it may cause sever to profound hearing loss. Gene like MT-TS and MT-RNR1 causes deafness. Several mutation have been identified which are, A7445G, 7472insC, T7510Cand T7511C which may cause deafness.

Table of Mitochondrial deafness, related gene and their mutation.

Gene	Mutation	Type
MT-RNR1	1494C>T 1555A>G	Sensorineural/severity variable
MT-TS1	7445A>G 7472insC  7510T>C 7511T	Sensorineural/ severity variable
MT-CO1	7444G>A	Sensorineural

 X-linked deafness

X-link deafness prefix as (DFNX) nearly 1 % deafness cases are caused by X-linked deafness. Almost 6 gene loci are presently identified, only 3 gene associated with deafness and present on X-chromosome, more over it is much rear. PRPS1 gene located on locus DFNX1 at Xq22 arm, POU3F4 which located on DFN3 at Xq21.1, and DMD located on Xp21.2 at locus DFNX4.

 Table of X-linked loci related gene and deafness.

Locus	Gene	Type
DNFX1   (DNF2)	PRPS1	Sensorineural
DNFX2 (DFN3)	POU3F4	Mixed
DFNX4 (DFN6)	DMD	Sensorineural

Autosomal dominant hearing loss

Autosomal dominant prefix as (DFNA), It causes 20% of non-syndromic hearing defect. About 54 gene loci have been identified, which are located on different chromosome, from which 19 genes responsible for autosomal dominant deafness. Most common genes are GJB3, GJB2, GJB6, POU4F3 and MYO7A.  It is extremely heterogeneous, and can be transfer either when one copy of alter gene is present.  NSADHL mainly non-congenital, or post-lingual, progressive and severe to profound but with some exception like DFNA3, DFNA8 and DFNA12 which may cause pre-lingual hearing loss.

Table of NSADHL, related locus their gene and type deafness.

Locus	Gene	Type
DFNA1	DIAPH1	Post-lingual/sensorineural/progressive
DFNA2	KCNQ4GJB3	Post-lingual/Progressive/sensorineural  Post-lingual/ progressive/sensorineural
DFNA3	GJB2 GJB6	Per-lingual/mild-to-profound/ progressive/ sensorineural
DFNA4	MYH14	Post-lingual/sever to profound /sensorineural  /progressive
DFNA5	DFNA5	Post-lingual/monogenic /sensorineural / progressive/ age related
DFNA6/14/38	WFS1	Per-lingual/ sensorineural
DFNA8/12	TECTA	Pre-lingual/ moderate to severe/  stable or non-progressive/ sensorineural
DFNA9	COCH	Post-lingual/sensorineural/progressive /profound

Autosomal recessive hearing loss

Autosomal recessive prefix as (DFNB), It accomplish major portion of non-syndromic hearing loss up to 80%. Currently 67 gene loci have been identified for it, Up to 700 mutation identified on 42 gene loci present on various chromosome which causes deafness the well-known genes are MYO7A, GJB2 and GJB6. As many of the world population 50% ARHL occur due to mutation in Gjb2 and remaining are the contribution of other mutated gene. Most of the ARNSHL may cause pre-lingual severe-to-profound hearing loss with exceptional cases like DNFB8.

Table of autosomal recessive loci and their related gene.

Locus	Gene	Type
DFNB1	Gjb2 Gjb6	Sensorineural/pre-lingual/ congenital/sever to profound
DFNB2	MYO7A	Pre-post lingual /sensorineural / severe-to-profound
DFNB3	MYO15A	Sensorineural/sever to profound
DFNB4	SLC26A4	Sensorineural or mixed /progressive/ pre-lingual/ post lingual
DFNB6	TMIE	Pre-lingual/sensorineural
DFNB7/11	TMC1	Sensorineural/profound/ congenital
DFNB8\10	TMPRSS3	Pre-lingual/post-lingual/Sensorineural
DFNB9	OTOF	Neural/profound/pre-lingual/

 

Figure represent the Genetic and Environmental, Syndromic and Non-syndromic, ADNSHL, ARNSHL, X-Linked and Mitochondrial contribution on the basis of percentage

Treatment of Hearing Loss

Hearing loss after examination can be cured by the following treatment based in the cause and severity of once hearing loss.

Surgical procedure:  this procedure medical intervention after examination the specialist perform surgery, when the abnormalities occur in middle and inner ear due to some infection or abnormalities in eardrum or ossicles (ear bones).

Cochlear implantation:  it is also a surgical implantation of cochlea due to some defect in it.

Medication:  if the hearing loss is due to any infection, it will treated by medication.