Intellectual and Behavioral Phenotypes of Smith-Magenis Syndrome: Comparisons between Individuals with a 17p11.2 Deletion and Pathogenic Variant.

Aim: Smith-Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder caused by a 17p11.2 deletion or pathogenic variant in the gene. SMS is associated with developmental delay, intellectual disability (ID), and major sleep and behavioral disturbances. To explore how genetic variants may affect intellectual functioning and behavior, we compared intellectual and behavioral phenotypes between individuals with a 17p11.2 deletion and pathogenic variant.

Method: We reviewed available clinical records from individuals (aged 0-45 years) with SMS, ascertained through a Dutch multidisciplinary SMS specialty clinic.

Results: We included a total of 66 individuals ( = 47, 71.2% with a 17p11.2 deletion and = 19, 28.8% with a pathogenic variant) for whom data were available on intellectual functioning, severity of ID ( = 53), and behavioral problems assessed with the Child Behavior Checklist (CBCL, = 39). Median full-scale IQ scores were lower (56.0 vs. 73.5, = 0.001) and the proportion of individuals with more severe ID was higher ( = 0.01) in the 17p11.2 deletion group. Median total CBCL 6-18 scores (73.5 vs. 66.0, = 0.02) and scores on the sub-scales somatic complaints (68.0 vs. 57.0, = 0.001), withdrawn/depressed behavior (69.5 vs. 55.0, = 0.02), and internalizing behavior (66.0 vs. 55.0, = 0.002) were higher in the group.

Conclusion: The results of this study suggest that 17p11.2 deletions are associated with a lower level of intellectual functioning and less internalizing of problems compared to pathogenic variants. The findings of this study may contribute to personalized-management strategies in individuals with SMS.