Hearing loss (HL) is a common sensory disorder affecting millions globally. While many causes are environmental, such as noise exposure, injury, or infections, a substantial portion is rooted in a person’s genetic makeup. Genetic factors account for approximately 50% to 60% of childhood hearing loss cases in developed countries. Confirmation of a hereditary cause provides families with crucial information for medical management, prognosis, and family planning decisions.
Scope of Hereditary Hearing Loss
Hereditary causes represent a large portion of congenital (present-at-birth) hearing loss, making it one of the most frequent sensory disorders with a genetic origin. For children born with hearing loss, a genetic cause is identified in over half of the cases. Acquired hearing loss is often due to external events like certain medications, prenatal infections such as Cytomegalovirus (cCMV), or trauma.
Genetic hearing loss is categorized as non-syndromic or syndromic. Non-syndromic hearing loss is the most common form (about 70% of genetic cases), occurring as an isolated condition without other related medical symptoms. Syndromic hearing loss (the remaining 30%) is part of a syndrome that affects other organ systems, such as the eyes, kidneys, or heart.
Understanding Genetic Inheritance Patterns
The mechanisms by which hearing loss is passed down involve four primary patterns of genetic inheritance.
Autosomal Recessive Inheritance
The most common pattern for hereditary hearing loss is autosomal recessive inheritance, accounting for up to 80% of non-syndromic cases. An individual must inherit a copy of the altered gene from both parents to be affected. The parents usually have normal hearing and are known as unaffected carriers. When two carriers have a child, there is a 25% chance of the child inheriting both altered copies and developing hearing loss.
Autosomal Dominant Inheritance
The second most frequent pattern is autosomal dominant inheritance, where only one copy of the altered gene, inherited from a single parent, is sufficient to cause the condition. If one parent has this form of hearing loss, there is a 50% chance the condition will be passed to their child. This pattern often results in hearing loss that starts later in life, may progress over time, and often runs through multiple generations.
X-Linked and Mitochondrial Patterns
Less frequently, hearing loss can be inherited through X-linked or mitochondrial patterns. X-linked inheritance involves genes located on the X chromosome, meaning the condition often affects males more severely and earlier in life than females. Mitochondrial inheritance involves genes located in the mitochondria, the cell’s energy-producing structures, and is passed down exclusively from the mother to all of her children.
Key Genes and Associated Syndromes
Over 120 genes are currently identified as causes of non-syndromic hearing loss alone. The GJB2 gene is the most common cause of non-syndromic hearing loss, particularly the autosomal recessive form. This gene provides instructions for making the connexin 26 protein, which forms gap junctions allowing communication between inner ear cells. Mutations disrupt this communication, leading to sensorineural hearing loss.
In the syndromic category, two examples illustrate how genetic changes affect multiple systems. Usher Syndrome combines hearing loss with progressive vision loss due to retinitis pigmentosa. This is the most common cause of deafblindness and can also involve balance difficulties, as affected genes influence structures in both the inner ear and the retina.
Waardenburg Syndrome is often inherited in an autosomal dominant pattern and is characterized by hearing loss along with changes in pigmentation. These changes can manifest as a white forelock of hair, two different colored eyes (heterochromia), or patchy depigmentation of the skin.
Genetic Testing and Counseling
Genetic testing helps individuals and families understand the cause of hearing loss and its implications. The process involves analyzing a person’s DNA from a small sample of blood or a cheek swab to identify specific changes in associated genes. Modern technology can simultaneously screen for variants in a large panel of genes, sometimes covering over 124 known hearing loss genes.
Testing is frequently recommended for infants and children with confirmed hearing loss, as well as for prospective parents with a family history. Genetic counseling is provided to interpret the complex results and explain the inheritance pattern. A genetic counselor assesses the risk of recurrence in future children and helps families make informed decisions about medical management and family planning based on the specific genetic findings.