Towards understanding the range of SYNGAP1-associated phenotypes: A case series of 5 adults with SYNGAP1 mutations

Mutations in the SYNGAP1 gene are associated with developmental disabilities and epilepsy. The phenotype described to date has been one of mainly moderate to severe intellectual disability, epilepsy, aggressive behaviour and sleep problems. However, mutations in this gene have also been reported in individuals with schizophrenia although limited phenotypic data has been published in these cases. Here we describe 5 cases of individuals with mild intellectual disability and major mental illness where we have found missense mutations in SYNGAP1 predicted to be deleterious.

The 5 individuals were part of the MUIR cohort who were included in the UK10K study and were reported to have missense mutations in the SYNGAP1 gene. These mutations were confirmed by subsequent Sanger sequencing.

The five adults (aged 52 -77) described all have a mild intellectual disability (IQ 50-70); three of the five have epilepsy and four of the five are obese. In addition, two individuals have schizophrenia, 2 have unipolar major depression, and one has bipolar affective disorder.

This study suggests that mutations in the gene contribute to an even wider range of associated phenotypes than previously described. In particular, we describe phenotypes present in older adults with mutations in SYNGAP1.