Individuals with SMS present with a distinct pattern of mild to moderate intellectual disability, delayed speech and language skills, distinctive craniofacial and skeletal abnormalities, behavioral disturbances, and, almost uniformly, significant sleep disturbances1. Genetic alterations in RAI1 have also been linked to a number of neurodevelopmental disorders including Autism2,3. In fact, 90% of SMS patients meet diagnostic criteria for Autism at one point in their lives4,5.
The enrichment of RAl1 variants is suggestive of prevalence of sleep disturbances in Autism similar to that observed in SMS which could be driven via the same molecular pathways.
Further studies will help discern the role of RAl1 variants in Autism and particularly in patients with sleep disturbances.
If you know someone with a neurodevelopmental disorder who has experienced sleep-wake disturbances we can help in coordinating for an RAI1 genetic test.
(1) Polymeropoulos, C.M., Brooks, J., Czeisler, E.L. et al. Tasimelteon safely and effectively improves sleep in Smith-Magenis syndrome: a double-blind randomized trial followed by an open-label extension. Genet Med 23, 2426-2432 (2021). https://doi.org/10.1038/s41436-021-01282-y (2) https://www.sfari.org/funded-project/neurobiology-of-rai1-a-critical-gene-for-syndromic-autism-spectrum-disorders/ (3) Slager RE, Newton TL, Vlangos CN, Finucane B, Elsea SH. Mutations in RAI1 associated with Smith–Magenis syndrome. Nat Genet. 2003;33:466–8. (4) Huang W-H, Wang DC, Allen WE, et al. Early adolescent RAI1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith-Magenis Syndrome. Proceedings of the National Academy of Sciences. 2018;115(42): 10744-10749. Doi:10.1073/pnas.1806796115. (5) G Laje, et al., Autism spectrum features in Smith-Magenis syndrome. Am J Med Genet C Semin Med Genet 154C, 456–462 (2010).