PCDH15-related disorders

What are PCDH15-related Disorders?

PCDH15-related disorders represent a group of disorders associated with hearing loss with/without vision loss. This group of disorders does not affect intelligence or cause any other primary health problems.

Usher Syndrome Type 1F (USH1F)

Usher syndrome type 1F is an inherited disease that causes hearing loss, balance problems and difficulty with gaze stabilization (secondary to vestibulopathy), and progressive vision loss. Infants with USH1F are profoundly deaf in both ears typically at birth. They have severe balance problems that can lead to delayed development (children sit and walk at later ages and have difficulties sensing changes in speed or direction). In childhood or by early adolescence, individuals with USH1F will develop retinitis pigmentosa, an eye disease which causes night blindness and a gradual loss of peripheral vision. Eventually only the central vision remains, creating a “tunnel vision” effect. Central vision can be impaired too and can lead to blindness in a small number of people with the disease, in part due to the occasional development of cataracts.

DFNB23

Some mutations in USH1F have been reported in recessive nonsyndromic hearing loss and deafness (isolated hearing loss), referred to as DFNB23. Individuals with DFNB23 typically have severe-profound hearing loss at birth. Unlike other forms of hearing loss, DFNB23 does not affect movement or balance.

How common are PCDH15-related Disorders?

The global incidence is unknown for both conditions. The incidence/prevalence of Usher syndrome type I overall has been estimated in a few countries. In most countries, the frequency ranges from ~1 in 45,000 to ~1 in 65,000, with the exception of Germany where the frequency is ~1 in 90,000. Approximately 7-12% of people with Usher syndrome type I have USH1F. There are regions where founder effects (high frequency of disease because the group arose from a small, possibly isolated population) occur. Individuals of Ashkenazi Jewish descent have been noted to have one common mutation with an estimated carrier frequency of ~1 in 134 individuals. In the Hutterite population, ~1 in 40 individuals is a carrier of a different common mutation.

DFNB23 is a rare disorder. It has only been reported in 5 families, and the global incidence is unknown. Other presentations of or variability in this disorder may not be recognized as of yet.

How are PCDH15-related Disorders treated?

There is no cure for PCDH15-related disorders, however early treatment is important to give an affected child the best opportunity to develop communication skills. While a child is young, his or her brain is most receptive to learning language, either spoken or signed. It is also important to take advantage of the time when the child’s vision is normal.

People with Usher syndrome type 1F generally do not respond to hearing aids, however cochlear implants may help regain some form of hearing. Sign language is a good option for communication. Specialists can introduce other tools and methods of instruction available to people with hearing loss. It is often helpful if the whole family undergoes such instruction and, as a family unit, helps the child adapt.

For those individuals that develop vision loss, visual aids and specialized instruction (for example in tactile signing) help children adapt to their limited vision. Individuals can be prone to accidental injury due to their vision loss and balance problems. Well-supervised participation in sports may help an individual with Usher syndrome type 1 compensate for balance issues, but swimming may be particularly difficult and strategies to ensure safety are needed. Use of UV-A and UV-B blocking sunglasses is recommended, and other optical aids may increase eye comfort. Therapy with vitamin A palmitate may slow retinal degeneration for some.

What is the prognosis for a person with a PCDH15-related Disorder?

Usher syndrome type IF results in severe hearing and vision impairment and DFNB23 results in hearing impairment only. However, neither condition affects one’s lifespan or intelligence.