Intellectual and Behavioral Phenotypes of Smith–Magenis Syndrome: Comparisons between Individuals with a 17p11.2 Deletion and Pathogenic RAI1 Variant

Smith-Magenis syndroom: verschillende oorzaken, uitingen en aanpak

Wetenschappelijk artikel in Genes. Als je iemand met het Smith-Magenis syndroom (SMs) wilt begeleiden en behandelen, dan is het goed om te weten wat de precieze oorzaak is namelijk of diegene een RAI1-mutatie of een 17p11.2-deletie heeft. Het onderzoek laat zien dat het belangrijk is om de oorzaak van SMs te kennen. Want die oorzaak kan invloed hebben op het IQ, de mate van verstandelijke beperking en het soort gedragsproblematiek. Dit kan om een verschillende aanpak vragen. 

Abstract: Aim: Smith–Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder caused by a 17p11.2 deletion or pathogenic variant in the RAI1 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 RAI1 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 (n = 47, 71.2% with a 17p11.2 deletion and n = 19, 28.8% with a pathogenic RAI1 variant) for whom data were available on intellectual functioning, severity of ID (n = 53), and behavioral problems assessed with the Child Behavior Checklist (CBCL, n = 39). Median full-scale IQ scores were lower (56.0 vs. 73.5, p = 0.001) and the proportion of individuals with more severe ID was higher (p = 0.01) in the 17p11.2 deletion group. Median total CBCL 6–18 scores (73.5 vs. 66.0, p = 0.02) and scores on the sub-scales somatic complaints (68.0 vs. 57.0, p = 0.001), withdrawn/depressed behavior (69.5 vs. 55.0, p = 0.02), and internalizing behavior (66.0 vs. 55.0, p = 0.002) were higher in the RAI1 group.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 RAI1 variants. The findings of this study may contribute to personalized-management strategies in individuals with SMS.

Auteurs: Linders, van Eeghen, Zinkstok, van den Boogaard & Boot

Jaar: 2023

https://www.mdpi.com/2073-4425/14/8/1514

Een Nederlandse samenvatting over het onderzoek bij ’s Heeren Loo