Usher syndrome (US) is a genetic disorder combining two major sensory impairments: hearing loss and progressive vision loss. The hearing loss is typically sensorineural, caused by abnormalities within the inner ear’s nerve cells. Vision impairment is due to retinitis pigmentosa (RP), an eye disease. This progressive vision loss first presents as difficulty seeing at night, gradually leading to the loss of peripheral vision. Understanding the inheritance pattern is central to grasping how this condition is passed down through families.
Defining Autosomal Recessive Inheritance
Usher syndrome is inherited in an autosomal recessive pattern. “Autosomal” means the responsible gene is located on one of the 22 non-sex chromosomes, affecting males and females equally. In this pattern, an individual must inherit two copies of the altered gene to exhibit the condition. Humans receive two copies of every gene, one from each parent. For Usher syndrome to manifest, both copies of the specific gene must contain a mutation.
If a person inherits only one altered gene and one normal copy, the normal gene is usually sufficient to ensure proper function, preventing the disease from developing. This mechanism means the presence of a single normal gene effectively masks the effect of the mutated gene. The child only develops the syndrome when the altered gene from one parent is matched by the altered gene from the other parent. This contrasts with dominant inheritance, where only one copy of a mutated gene is required to cause the condition.
The Role of Carrier Parents
The inheritance of Usher syndrome most commonly involves two parents who are genetic carriers. A carrier possesses one normal and one mutated copy of the gene but shows no symptoms themselves. Because the carrier parents are unaffected, the condition can appear in a family with no prior history of the syndrome.
When two carrier parents reproduce, specific statistical probabilities apply to each pregnancy. The child has a 25% chance of inheriting the altered gene from both parents, resulting in Usher syndrome. There is a 50% chance the child will inherit only one altered gene, making them an asymptomatic carrier like their parents. The child also has a 25% chance of inheriting two normal copies of the gene, meaning they will be neither affected nor a carrier. These probabilities apply to each individual pregnancy, regardless of previous outcomes.
Gene Locations and Usher Syndrome Types
While the inheritance pattern is the same, the specific mutated gene determines the clinical type of Usher syndrome. Researchers have identified at least 11 different genes associated with the syndrome. A mutation in any one of these genes can lead to the condition by affecting proteins involved in the function of the inner ear’s hair cells and the retina’s light-sensing cells.
The syndrome is broadly categorized into three types based on the severity of hearing loss, balance issues, and age of onset. Type 1 is associated with severe hearing loss from birth and balance problems. Type 2 generally presents with moderate to severe hearing loss and no balance issues. The most common gene mutations are found in MYO7A for Type 1 and USH2A for Type 2, with USH2A being the most frequently mutated gene overall.
The specific gene affected influences the timing of vision loss and the degree of severity. For example, the MYO7A gene is located on chromosome 11, while the USH2A gene is found on chromosome 1. Type 1 vision loss typically appears in childhood, whereas Type 2 vision loss begins in the late teens or adulthood.