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

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.