The neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities due to germline mutations in the GNAI1 gene represents a rare, early-onset disease with a non-specific clinical manifestation.
Prevalence
The GNAI1-related neurodevelopmental disorder is a rare condition. Its worldwide, or population-specific prevalence is unknown. Only several tens of affected individuals carrying recurrent or unique germline GNAI1 mutations have been described in the literature so far
Inheritance
Almost all reported cases have virtually a de novo origin. To date, only one case of inherited causative mutation has been reported due to the low-level parental (maternal) mosaicism (< 10%; her phenotype is unknown)1. In general, parental mosaicism (a presence of mutations in a certain proportion of cells of tested tissues) should not be excluded, as it may represent a recurrence risk in any subsequent pregnancies2. The estimation of the recurrent transmission for de novo mutations is commonly reported as < 1%. This estimation may vary due to the parental origin, degree of mosaicism and the nature of affected tissue(s).
1. Muir AM et al. Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia. Genet Med. 2021;23(5):881-887.
2. Campbell IM et al. Parent of origin, mosaicism, and recurrence risk: probabilistic modelling explains the broken symmetry of transmission genetics. Am J Hum Genet. 2014;95(4):345-359.
GNAI1