Clinical features
Individuals with PVRL1mutations typically present cleft lip and/or palate, hidrotic ectodermal dysplasia (hair/nail/sweat gland involvement), and developmental defects of the hands (syndactyly); mild cognitive delay has been reported in some cases.
Reported pathogenic variants include recurrent loss-of-function changes (e.g., founder p.W185X and frameshift variants), consistent with impaired nectin-1 function.
Beyond the syndromic phenotype, heterozygosity for the founder p.W185X allele has been strongly associated with sporadic, nonsyndromic cleft lip with or without cleft palate; carriers are otherwise clinically unaffected and the absolute risk for any given pregnancy remains low.
Prevalence
The condition is very rare globally. A notable founder effect has been described in the indigenous population of Margarita Island, where the frequency has been estimated at ~1 in 2,000. Other affected families have been reported in different populations.
Genetic Counselling
Mutations in PVRL1 are inherited in an autosomal recessive manner. Affected individuals are typically born to unaffected carrier parents; consanguinity may be present in some families. The condition is exceptionally rare. Carrier testing for at-risk relatives and prenatal or preimplantation genetic testing are technically feasible once the familial variants are identified.
PVRL1