Distinct Neuropsychiatric Profiles Associated With 17p11.2 Deletions and RAI1 Variants in Smith-Magenis Syndrome

Retrospective genotype-stratified analysis of 52 SMS patients — delineation of two distinct neuropsychiatric trajectories by 17p11.2 deletion vs point RAI1 variant

In a series of 52 SMS individuals evaluated at CRMR GénoPsy (Lyon), 17p11.2 deletion (43 cases) is associated with marked intellectual disability (86%), severe externalizing behaviors (self-injury, hetero-aggressiveness), and dystonia, while RAI1 variants (9 cases) show relatively preserved cognition but increased internalizing vulnerability (anxiety 55%, social withdrawal 44%). ADHD and circadian rhythm disturbances are common therapeutic targets across both genotypes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This study from the French national reference center formalizes an actionable clinical distinction in SMS: RAI1 variant patients deserve particular attention to the anxiety and social dimensions, often under-recognized against more visible behavioral disorders. For clinicians, precise genotyping (deletion vs point variant) directly guides management.

Clinical impact: 1/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Journal quality: 1/1 → Total: 6/10