**1. Introduction**

Hearing loss (HL) is the most common sensory defect in human beings, affecting 1.86 in 1000 newborns around the *world* which half of it is due to genetic causes (Morton & Nance, 2006). HL can be syndromic or nonsyndromic. Individuals affected with syndromic form have additional clinical signs whereas nonsyndromic HL is not associated with other clinical signs and symptoms. All Mendelian pattern of inheritance have been observed in nonsyndromic HL (NSHL) including autosomal dominant (AD), autosomal recessive (AR), X-linked inheritance (XL) and mitochondrial inheritance (MT); autosomal recessive is the main form of NSHL, i.e. 75-85 % of NSHL show AR pattern in affected pedigrees.

As known, ear is the organ of hearing and balance. Hearing is dependent on a series of complex events. The ear has three anatomical parts including outer, middle and inner ear. The external ear which is composed of the auricle, ear canal and eardrum membrane collects sound waves and transmits them to the eardrum. Three tiny bones of middle ear (the ossicles) act as levers and conduct the sounds to the oval window, and finally through the cochlea (a snail-shaped organ) which has the auditory receptors (the organ of Corti) in the inner ear [Raphael & Altschuler 2003]. A collagen-based extracellular matrix, called tectorial membrane on top of the hair cells is vibrated by sound waves [Richardson et al., 2008]. Within the organ of Corti, physical vibrations produce a mechanoelectrical transduction which is detected by hair cells and these cells respond by producing electrical impulses. Nerves transmit these impulses to the brain where they are interpreted. Different sound frequencies stimulate the hair cells in different parts of the organ of Corti and lead to perception of different sound frequencies. Sounds are processed in both sides of the brain but the interpretation of the sounds takes place at the left side of brain. Sounds are heard at normal hearing thresholds between 0-20 dB across the 125-8000 Hz range while loss of more than 20 dB, is said to have hearing loss which is confirmed by measuring pure tone average (PTA) (average hearing sensitivity at 500, 1000 and 2000 Hz).

Nearly one hundred and twenty million people suffer from hearing impairment around the world. History of some important events about human hereditary HL is shown in table 1 [Nance & Sweeney, 1975; Wallis et al., 1988; Kimberling et al., 1990; Leon et al., 1992;

Genetics of Hearing Loss 213

and ear duct [Willems, 2004; Shin et al., 2011].

and increased blood bilirubin [Willems, 2004].

a. factors before birth including congenital infections (e.g. toxoplasmosis, measles, syphilis, smallpox, cytomegalovirus, herpes virus), congenital deformities of aurical

b. factors during birth including prematurity and low birth weight (less than 1500gr)

c. factors affecting after birth including infections and bacterial meningitis, mumps, otitis media, blood infection and autotxic drugs such as aminoglycosides, head

2. Genetic HL: the genetic basis of HL is known for more than 100 years. In the early decade of 1800s, the Irish physician William Wild explained the inheritance of HL. His theory differentiated between dominant and recessive inheritance. He also observed

Intensity of the sound is calculated in units of decibel (dB), which is logarithm intensity of the sound wave to a reference sound intensity divided by ten [Willems, 2004]. The normal

a. Conductive HL: Factors affecting sound transmission including aurical, ear canal, eardrum, outer and middle ear bones to the cochlea cause conductive HL. The most common causes of conductive HL are the external and middle ear congenital abnormalities such as atrophy and dysplasia, duct obstruction, impacted cerumen,

b. Sensorineural HL (SNHL): The disorder occurs in the auditory nerve or the cochlea. In other words, the abnormalities occur some place between the hair cells and auditory

b1. congenital causes such as rubella, syphilis, Usher syndrome, Alport Syndrome, Waardenburg syndrome and autosomal dominant and recessive sensorineural

b2. acquired factors: Infections such as measles, cytomegalovirus, bacterial meningitis, autotoxicity of drug consumption, noise pollution including long-term exposure,

c. Mixed HL: in this type of hearing loss, conductive and sensorineural problems are observed simultaneously. Infections such as tuberculosis, some syndromes and skull

a. Prelingual: Loss of hearing occurs before speech is acquired. If a child has a congenital

c. Presbycusis or age-related HL (ARHL): Epidemiologic studies show that nearly 25 % of 60 year olds and more than 50 % of 80 year ages undergo ARHL [Dror & Avraham,

injury or skull fracture which lead to anesthesia [Willems, 2004].

hearing threshold is 15 dB. A regular conversation occurs at level of 45 to 60 dB.

that men showed more X-linked transmission [Willems, 2004].

otitis, middle ear and Tympanic membrane problems.

brain regions. The most common causes of SNHL are:

presbycusis and sudden idiopathic HL [Willems, 2004].

On the basis of the age of onset, HL is divided into the following types:

hearing impairment, he would not be able to speak normally. b. Postlingual: Loss of hearing occurs after speech is developed.

deafness [Friedman et al., 2003].

fractures may also cause mixed HL.

2009; Huang & Tang, 2010].

**2.4 Age of onset** 

**2.2 Severity** 

**2.3 Position of damage** 

Guilford et al., 1994; Kelsell et al., 1997; Lynch et al., 1997; Eudy et al., 1998; Gorlin, 2004; Dror & Avraham 2009].


\*Autosomal domiant non syndromic hearing loss, ■Autosomal recessive nonsyndromic hearing loss

Table 1. Chronological events regarding hereditary HL.

One of the main programs of the World Health Organization (WHO) is to encourage countries for the prevention of deafness [Emery, 2003]. Understanding the molecular and genetic mechanisms of HL may lead to development of new therapy and treatment approaches. Here, we review major causes leading to either syndromic or nonsyndromic HL.
