16p11.2 deletion and duplication syndromes

16p11.2 deletion and duplication syndromes are typically characterized by developmental delay, intellectual disability, behavioral and psychiatric concerns, weight issues, congenital anomalies, and epilepsy. The 16p11.2 region of the chromosome contains many low-copy repeats where atypical recombination events occur, and lead to copy number variations (CNVs). Vos et al. report on 100 cases with pathogenic 16p11.2 CNVs that were seen by the genetics clinic at Amsterdam University Medical Centers between 2017 and 2022. There is variable presentation reported based on the type of and region location of the pathogenic mutation. 62% of the cases in the study were caused by a 600 kb deletion in the 29.6-30.2 Mb region of chromosome 16, which is defined as the typical B4-B5 presentation of 16p11.2 deletion syndrome. The majority of these deletions arose de novo and presented with developmental delay, speech delay, autistic features, high BMI, and hyperphagia. The most common type of 16p11.2 duplication in this cohort (10% of all cases) was duplication in the same area of chromosome 16 (29.6-30.2 Mb). These cases tended to occur de novo, and 30% of them presented with neonatal feeding issues. Some of the more notable symptoms recorded in these cases were developmental and intellectual delay, sleeping problems, and issues with their vision. The second common variant of 16p11.2 deletion in this cohort was a 220 kb deletion in the 28.8-29 Mb (BP2-BP3). This group of patients presented with delayed motor and speech development, obesity, sleeping problems, and hyperphagia. This review of 100 cases proves that 16p11.2 deletion syndrome demonstrates significant clinical variability depending on the type and specific location of the pathogenic mutation. Possible genetic obesity was a common presentation of 16p11.2 deletion syndrome and can be used as an indication for genetic testing to be ordered. Patients presenting with 16p11.2 duplication syndrome tended to be underweight. Patients with the 16p11.2 BP2-BP3 deletions are eligible for setmelanotide clinical trials to possibly help treat the obesity. Other than medication, lifestyle changes such as exercise and a healthy diet are recommended for patients with 16p11.2 deletion and duplication syndromes. Early diagnosis is vital for the treatment options and clinical course of 16p11.2 deletion and duplication syndromes in each patient.

Vos et al. “Evaluation of 100 Dutch cases with ; from clinical manifestations towards personalized treatment options” . “Europ. J. Human Genetics” 2024, v. 32 (11), 1387-1401.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact info@chromodisorder.org