Families

What is PVRL1-related syndrome?
PVRL1-related syndrome (also called CLPED1) is a rare genetic condition caused by changes (pathogenic variants) in the PVRL1gene, which makes nectin-1, a protein that helps cells stick together during early development. Typical features can include cleft lip and/or cleft palate, webbing of the fingers and/or toes, sparse, fragile hair (including thin eyebrows/eyelashes), dental differences (late tooth eruption, small or missing teeth), and thick, dry skin on the palms and soles. Fingernails are often normal but can be thin or irregular in some people. Learning and development are usually normal, but in a few families mild developmental delay has been reported. Most individuals have a normal life span. The condition is autosomal recessive (usually both parents of an affected individual are healthy carriers).

People who carry one copy of the PVRL1p.W185X change may have a slightly higher chance of having a baby with an isolated cleft lip (with or without cleft palate), but most carriers have healthy, unaffected children.

How many people are affected?
The condition is exceptionally rare worldwide. A higher frequency has been reported in the indigenous population of Margarita Island (Venezuela) due to a historical “founder” variant in the community. Once the family’s genetic variant is known, carrier testing for relatives and prenatal or pre-implantation genetic testing can be offered.