Genetic hearing loss refers to hearing impairment that arises from mutations in an individual’s genes. These genetic changes disrupt the auditory system, leading to varying degrees of hearing loss. Genetic factors account for approximately 50-60% of hearing loss cases in children.
How Genetic Hearing Loss is Inherited
Genetic hearing loss can be passed down through families in several distinct patterns, each determined by how the altered gene is located and expressed.
Autosomal Dominant Inheritance
One common pattern is autosomal dominant inheritance, where only one copy of an altered gene from one parent is sufficient for the condition to manifest. There is a 50% chance for each child to inherit the condition from an affected parent. Males and females are equally likely to be affected.
Autosomal Recessive Inheritance
Autosomal recessive inheritance requires two copies of the altered gene—one from each parent—for hearing loss to appear. Parents who carry one copy of the altered gene have normal hearing, but each of their children has a 25% chance of inheriting both copies and developing hearing loss. This pattern accounts for 75-80% of non-syndromic genetic hearing loss cases.
X-linked Inheritance
X-linked inheritance involves genes on the X chromosome. Males, with only one X chromosome, are more likely to exhibit the condition if they inherit an altered gene. Females, with two X chromosomes, may be carriers without symptoms or experience milder forms of hearing loss. Each son of a female carrier has a 50% chance of inheriting the altered gene and the condition.
Mitochondrial Inheritance
Mitochondrial inheritance is a unique pattern where genetic material is passed down exclusively from the mother. Mitochondria contain their own DNA, and mutations in this DNA can lead to hearing loss. All offspring of a mother with a mitochondrial DNA variant are at risk of inheriting it, while offspring of affected males are not.
Syndromic Versus Non-Syndromic Genetic Hearing Loss
Genetic hearing loss is broadly categorized into two main types: non-syndromic and syndromic, based on the presence or absence of other associated medical symptoms.
Non-Syndromic Hearing Loss
Non-syndromic hearing loss refers to hearing impairment that occurs in isolation, without other associated medical problems or physical characteristics. This form accounts for 70-80% of inherited hearing impairment. Its characteristics can vary, affecting one or both ears, ranging from mild to profound, and may be stable or progressive.
Syndromic Hearing Loss
Syndromic hearing loss occurs as part of a broader set of symptoms affecting other bodily systems. These can include issues with vision, kidney function, heart problems, or other physical abnormalities. Approximately 15-30% of hereditary hearing impairments are syndromic. Over 400 syndromes are known to include hearing impairment as a feature, and these can present with varying severity.
Inheritance Patterns in Both Forms
Both non-syndromic and syndromic forms of genetic hearing loss can follow any inheritance pattern, including autosomal dominant, autosomal recessive, X-linked, or mitochondrial. While non-syndromic hearing loss is predominantly autosomal recessive, syndromic forms can also be transmitted via autosomal dominant or X-linked patterns. This distinction is helpful for diagnosis and management, as other symptoms often guide further medical evaluation.
Common Genetic Forms of Hearing Loss
Specific genetic conditions illustrate the diverse ways hearing loss can manifest.
GJB2-Related Hearing Loss
GJB2-related hearing loss is the most common cause of non-syndromic genetic hearing loss. Mutations in the GJB2 gene affect intercellular communication in the inner ear. This leads to severe-to-profound prelingual hearing loss, and the specific gene change can predict severity or progression.
Usher Syndrome
Usher syndrome is a common syndromic form, characterized by both hearing loss and progressive vision loss due to retinitis pigmentosa. This condition is inherited in an autosomal recessive manner and is the most frequent syndrome affecting both hearing and vision. There are three main subtypes: USH1 involves profound bilateral deafness and severe vestibular dysfunction at birth, while USH2 presents with moderate to severe hearing loss at birth and later onset retinitis pigmentosa.
Pendred and Waardenburg Syndromes
Pendred syndrome is another syndromic form, inherited in an autosomal recessive fashion through mutations in the SLC26A4 gene. Individuals with Pendred syndrome experience hearing loss, accompanied by inner ear abnormalities like an enlarged vestibular aqueduct, and thyroid gland issues. Waardenburg syndrome is a syndromic condition inherited in an autosomal dominant pattern. It is characterized by varying degrees of hearing loss, changes in pigmentation such as a white forelock or different colored eyes, and distinct facial features.
Mitochondrial Hearing Loss
Mitochondrial hearing loss, such as that associated with the A1555G mutation in the MT-RNR1 gene, is linked to increased sensitivity to aminoglycoside antibiotics. This mutation can lead to severe to profound bilateral hearing loss within days or weeks of exposure to these medications, even with a single dose. This form of hearing loss is inherited maternally. Identifying these specific genetic forms through testing can provide a more targeted understanding of the condition and guide appropriate management strategies.