De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability

Original research article by M.J. Parker et al. (2015).

Read the article here.

A previous study done by Hamdan et al. (2009) identified three de novo SYNGAP1 mutations, linking them to intellectual disability (ID) and describing them as nonsyndromic, or unrelated to any specific syndrome or condition. Through exome sequencing of ten affected individuals and their parents, the more recent study done by Parker et al. was able to identify eight SYNGAP1 mutations and one SYNGAP1 deletion in individuals with undiagnosed developmental disorders. Ranging from age 3 to age 14, the affected individuals all exhibited a range of developmental delays and distinct facial features. A majority of the affected individuals exhibited behavior problems, such as aggression and excitability, and seven of the ten individuals were also reported as having seizures. While the features exhibited in the individuals with a SYNGAP1 mutation or deletion varied, Parker et al. suggest that the clinical features seen in affected individuals (see table below) are consistent enough to point to the potential diagnosis of a syndrome caused by SYNGAP1 mutations.  However, more clinical research with a larger group of SYNGAP1 patients will be needed to determine the degree to which this genetic change affects medical, behavioral, and developmental aspects of the individual.