SNP Shot: Genomic Insights

Nonsyndromic hearing loss refers to hearing impairment, either partial or complete, that occurs without any other related medical issues or symptoms. This is different from syndromic hearing loss, which is characterized by hearing loss alongside other signs and symptoms affecting different parts of the body.

Nonsyndromic hearing loss can be categorized in various ways, commonly by its mode of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-linked (DFNX), or mitochondrial. Mitochondrial inheritance in this case does not have a specific designation. Each of these categories includes several subtypes. The subtypes within DFNA, DFNB, and DFNX are numbered based on the order of their discovery. For example, DFNA1 was the first identified type of autosomal dominant nonsyndromic hearing loss.

The characteristics of nonsyndromic hearing loss differ depending on the specific type. The hearing loss may affect one ear (unilateral) or both ears (bilateral). The severity can range from mild, where individuals have difficulty understanding soft speech, to profound, where even loud noises cannot be heard. Severe-to-profound hearing loss is often referred to as "deafness." The hearing loss can be stable, remaining consistent over time, or progressive, worsening with age. Certain types of nonsyndromic hearing loss exhibit distinct patterns, such as being more pronounced at high, middle, or low frequencies.

Most types of nonsyndromic hearing loss are sensorineural, meaning they are caused by permanent damage to the structures within the inner ear. The inner ear processes sound and transmits this information to the brain via electrical signals. Less frequently, nonsyndromic hearing loss is conductive, resulting from problems in the middle ear. The middle ear contains three small bones that transmit sound vibrations from the eardrum to the inner ear. Some forms of nonsyndromic hearing loss, particularly DFNX2, involve changes in both the inner and middle ear, resulting in a mixed hearing loss.

The onset of nonsyndromic hearing loss can occur at any point in life, from infancy to old age, depending on the specific type. Hearing loss present before a child learns to speak is classified as prelingual or congenital. Hearing loss that develops after speech acquisition is considered postlingual.

Inheritance:

As mentioned, nonsyndromic hearing loss can be inherited through different patterns. Autosomal recessive inheritance accounts for 75 to 80 percent of cases, requiring both copies of the relevant gene in each cell to have mutations. Individuals with autosomal recessive hearing loss typically have parents who each carry one copy of the mutated gene but do not experience hearing loss themselves. Another 20 to 25 percent of cases are inherited in an autosomal dominant manner, where only one copy of the altered gene in each cell is enough to cause the condition. Individuals with autosomal dominant hearing loss usually inherit the altered gene from a parent who also has hearing loss. X-linked inheritance is responsible for 1 to 2 percent of cases. In X-linked conditions, the mutated gene is located on the X chromosome, one of the sex chromosomes. Males with X-linked nonsyndromic hearing loss tend to experience more severe hearing loss earlier in life compared to females who inherit the same gene mutation. Notably, fathers cannot pass X-linked traits to their sons. Mitochondrial inheritance, resulting from changes in mtDNA, accounts for less than 1 percent of nonsyndromic hearing loss cases in the United States. Mitochondrial inheritance, also called maternal inheritance, affects genes contained in mtDNA. Because only egg cells contribute mitochondria to the developing embryo, children can only inherit mtDNA mutations from their mother. These conditions can appear in every generation and affect both males and females, but fathers cannot pass mtDNA-related traits to their children. In some instances, hearing loss occurs in individuals with no family history of the condition. These cases are considered sporadic, and the cause is often unknown. Hearing loss resulting from environmental factors is not inherited.