An exploratory study on Smith Magenis syndrome: differences in weight and lipid profiles between patients with a 17p11.2 deletion and patients with a RAI1 gene mutation

Abstract

Background: Smith Magenis syndrome (SMS) is a genetic neurodevelopmental disorder caused by an interstitial deletion of 17p11.2 or a mutation in the RAI1 gene, located in the 17p11.2 region. SMS is characterized by intellectual disability, sleep disturbances, behavioural problems and several somatic conditions including obesity and lipid disorders. To date, few studies have addressed genotype-phenotype associations. The aim of this study was to enhance the knowledge on the relationship between body weight, lipid profiles, and the cause of SMS (deletion vs. RAI1 mutation). Methods: A retrospective chart study was conducted of 38 individuals with SMS (27 with a 17p11.2 deletion and 11 with a RAI1 mutation) aged 2-37 years (10 aged ≥18 years at last assessment) There were no betweengroup differences in age (p=0.25) or sex (p=0.47). Data concerning genotype, body mass index (BMI) and lipid profiles were collected during regular visits and extracted by systematic chart reviews. Results: Overweight was present in 30% of patients with a deletion and in 73% of patients with a RAI1 mutation (p=0.03). After correction for age and sex, individuals carrying a RAI1 mutation were more likely to have overweight compared to those carrying a 17p11.2 deletion (OR=5.75, 95% CI=1.17-28.11). The median BMI in adults was 24.6 kg/m2 (IQR=23.7-32.6). Abnormal lipid profiles, available for a subset of the cohort (n=24), were only found in patients with an interstitial deletion. Conclusion: Our results add to the previously reported, and seemingly conflicting, findings suggesting a higher risk on overweight in those with a RAI1 mutation, and a higher risk on lipid profile abnormalities in those with a 17p11.2 deletion. Further research in larger sample sizes is required to explore additional genotype-phenotype associations.