PCDH15-related disorders are a group of conditions linked to hearing loss, with or without vision loss. These disorders don’t affect intelligence or cause other major health issues.
Usher syndrome type 1F (USH1F) is a disease that leads to hearing loss, balance problems, and trouble with gaze stabilization (because of issues with the inner ear). Babies with USH1F having hearing loss, usually from birth. They also have significant balance problems, which can affect their development—like sitting and walking happening later and having trouble sensing changes in speed or direction. By childhood or early adolescence, people with USH1F will develop retinitis pigmentosa, an eye disease causing night blindness and a gradual loss of side vision. Eventually, only central vision remains, creating a “tunnel vision” effect. In some cases, central vision can be affected, leading to blindness, partly because of cataracts. Some changes in USH1F have been found in nonsyndromic hearing loss (isolated hearing loss), known as DFNB23. Individuals with DFNB23 usually have severe to profound hearing loss at birth. Unlike other hearing loss forms, DFNB23 doesn’t impact movement or balance. There’s no cure for PCDH15-related disorders, but early treatment is crucial to give affected children the best chance to develop communication skills. For those with vision loss, visual aids and specialized instruction (like in tactile signing) can help kids adapt.
This group of conditions is caused by pathogenic (disease-causing) variants in the PCDH15 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 78 chance to be a carrier.