Abstract Background Smith Magenis Syndrome is either due to a deletion in 17p11.2 locus or to a pathogenic variant in RAI1 gene and is associated with a higher risk of neurodevelopmental disorder. We performed a systematic review to assess the prevalence of neurodevelopmental disorders (autism spectrum disorder, attention deficit hyperactivity disorder, intellectual developmental disorder, specific learning disabilities) in Smith Magenis Syndrome as a main outcome. We described the methods used to identify a neurodevelopmental disorder in this population and assessed a phenotype-genotype correlation as secondary outcomes. Methods & results Main electronic databases were searched on January 31 st , 2024. We considered original articles published in peer-reviewed journals. We selected studies with data concerning the prevalence of neurodevelopmental disorders in people with Smith-Magenis Syndrome. Quality was assessed based on sample identification, confirmation of syndrome, assessment of neurodevelopmental disorders and data coverage. 1941 articles were identified and 14 were included in this review. Data were synthesized and displayed as descriptive tables. No meta-analysis was performed due to the paucity of studies. In total, 451 patients presenting with Smith Magenis syndrome were assessed for neurodevelopmental disorders. 6 studies ( n =220 patients) assessed autism spectrum disorder characteristics with prevalence ranging from 14% to 95%, and mean prevalence of 43% and 80% for deletion and RAI1 samples respectively. 6 studies assessed attention deficit hyperactivity disorder characteristics ( n = 174 patients). Only one study assessed ADHD using standardized clinical criteria, reporting 100% prevalence. Other studies assessed impulsivity, hyperactivity, attention deficit with mean proportions of 78%, 76% and 96% respectively. 9 studies reported IDD prevalence, ranging from 67% to 100%. For deletion carriers, pooled prevalence was 93%, mostly moderate (43%), while 80% was reported for RAI1 carriers, mostly mild (69%). Specific learning disabilities were described for 9% of deletion 17p11.2 patients. Methods of assessment were very heterogeneous, consisting in the main limit of this study along with the paucity of articles included. Conclusions In addition to IDD, ASD and ADHD phenotypes are often observed in Smith Magenis syndrome, with RAI1 carriers affected even more frequently despite a higher cognitive level. This systematic review highlights the need to systematically screen people with Smith Magenis syndrome for attention deficit hyperactivity disorder and autism spectrum disorder in addition to cognitive functions. Smith Magenis syndrome is a relevant model to further study physiopathology of neurodevelopmental disorder. Trial registration (PROSPERO no.: CRD42024512675).
Boiroux et al. (Mon,) studied this question.