It is now possible to identify a specific genetic disorder in around 50% of individuals with intellectual disability. However, we are at a very early stage of understanding the links between each genetic disorder, brain development, cognition and everyday difficulties.

De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. To address this, researchers from the MRC CBU travelled across the UK to visit families of 14 young people with ID caused by STXBP1 mutations. They collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics, using standardised questionnaires supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes.

The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. To account for the potential impact of global cognitive impairment, secondary comparison was made to an ability-matched subset of the ID group. In comparison to the ability-matched ID group, severity of receptive language and social impairments discriminated the STXBP1 group.

A particularly striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. Participants in the STXBP1 group consistently showed great enjoyment of social interactions with family members, and demonstrated reciprocal behaviours such as sharing and turn-taking. Members of the research team also observed that, participants wanted to engage with the researchers (a novel stranger within the participants’ home) particularly in social activities such as drawing, dancing, singing, and playing games.

To take these observations forward, our group is now planning to explore the   mechanisms linking motor, speech, and social development in STXBP1 and other disorders caused by genes in the synaptic vesicle cycling pathway. Understanding the developmental emergence of behavioural characteristics in these groups could help to focus clinical assessment and management, with the long-term aim of     improving outcomes for patients and families.

The full article can be read here:  https://link.springer.com/content/pdf/10.1186%2Fs11689-019-9278-9.pdf