Professionals

Prevalence
PRPF8-related neurodevelopmental disorder is rare. The original report described 14 individuals with heterozygous, predominantly de novo, missense or loss-of-function variants. Population prevalence and penetrance are not established.

Clinical characteristics
Reported features of the neurodevelopmental presentation include developmental delay or intellectual disability, autism or behavioural differences, hypotonia and feeding difficulties. Structural cardiac abnormalities, brain imaging abnormalities and dysmorphic features have also been reported.

PRPF8also causes autosomal dominant RP13, a principally ocular disorder characterised by night-vision difficulty, peripheral visual-field loss and progressive retinal degeneration.

Molecular characteristics
Heterozygous missense and predicted loss-of-function variants have been reported in the neurodevelopmental presentation. RP13-associated variants cluster near the C terminus of the protein. A homozygous missense variant has been proposed in one family as a recessive association; this remains unconfirmed.

Genetic Counselling
For an established dominant pathogenic variant, transmission risk is 50% in each pregnancy. When parental blood testing is negative, recurrence is usually low but not zero, because parental germline mosaicism remains possible.

Management
Treatment is symptomatic and multidisciplinary. There is no validated PRPF8-specific surveillance protocol.