ESPE Abstracts

Background: 16p11.2 microdeletion is most common chromosomal anomaly associated with syndromic obesity. The presence of a large number of flanking segmental duplications/low-copy repeat sequences with a high degree of sequence identity in the short arm of chromosome 16 (16p) leads to recurrent deletions and duplications as a consequence of non-allelic homologous recombination. A recurrent 600kb microdeletion is one of the most frequent genomic imbalances in 16p11.2 (~600kb) associated with abnormal phenotypes including neurodevelopmental disorders, autism spectrum disorder (ASD) and obesity. The 16p11.2 microdeletion (OMIM ID:611913; ORPHA:261211) is one of the major causes of syndromic obesity.

Material and Methods: it was performed a retrospective analysis of patient medical records of 45 patients with 16p11.2 deletions obtained by Agilent 180K oligonucleotide array-comparative genomic hybridization (array-CGC) and/or multiplex ligation-dependent probe amplification (MLPA). The study was performed at Pediatrics Hospital of Coimbra during the period of 2010-2022.

Results: From a total of 45 patients, 37 (82%) were under 18 years old, and 33 (91.6%) showed a deletion in the classical region of 16p11.2 (29,562-30,192bp). Thirty one (84.6%) were referred to our consultation from intellectual disability/learning difficulties and in those, only 6 (18%) was also reported to have obesity. Although the phenotype of individuals with the deletion can be variable, all patients showed at least one clinical finding typical of 16p11.2 deletion: cognitive impairment, language delay, autism or obesity. Seven from 28 (25%) individuals between 5 and 19 years old (WHO reference 2007) have body mass index (BMI) >2 standard deviation (SD) and 7 (25%) were overweight with BMI>1 SD. One (11,1%) from 9 individuals under 5 years old was obese (BMI>3SD).

Conclusion: Although the phenotype of 16p11.2 microdeletion syndrome shows a high variability, it represents the second most frequent genetic cause of obesity. In our cohort 21.6% were obese and 25% were overweight. The obesity observed in this population may be explained by the haploinsufficiency of one or more of the 30 genes present in this region. On the other hand, it is known that individuals with intellectual disability or autism have a higher predisposition for obesity, possibly due to the involvement of one or more pathways.