Schinzel-Giedion syndrome: communication, feeding and motor skills in 16 individuals.

Schinzel-Giedion Syndrome (SGS) is a rare neurodevelopmental disorder caused by pathogenic SETBP1 gain-of-function variants. SGS medical features have been well described. Associated skills critical to quality of life have such as communication, feeding, and motor skills are yet to be characterised. Here we used standardised caregiver report tools to characterise these skills as well as the medical features, in 16 children with SGS (median = 5 years, 7 months, range 6 months to 12.5 years). Vineland-3 scores reflected severe impairment in communication, daily living, socialisation and motor skills. Average receptive and expressive language skills were equivalent to a 0-to-1-month-old. Average motor skills were slightly stronger with age equivalents of 2-months-old for gross motor skills and 4-months for fine motor skills. 13/16 (81%) children could attend to someone's voice, and 15/16 (94%) could make happy vocalisations. One individual (6%) could follow basic instructions. Despite a relatively homogenous phenotype, some children presented with relative strengths when compared to the rest of the cohort. Our expanded phenotype of SGS allows better targeted therapies and supports, highlighting the importance of early feeding intervention and augmentative and alternative communication (e.g., assistive technology for communication). Given the severity of the SGS profile, our data highlight the need for sensitive measurement tools for detecting subtle skill changes in SGS in response to precision medicine interventions.