We found a higher rate of perinatal complications in PWS syndrome compared with the general population. No significant differences in the genetic subtypes were noted except for a higher maternal age and pre-pregnancy weight in the UPD subgroup.

Obesity is a complex multifactorial disorder with genetic and environmental factors. There is an increase in the worldwide prevalence of obesity in both developed and developing countries. The development of genome-wide association studies (GWAS) and next-generation sequencing (NGS) has increased the discovery of genetic associations and awareness of monogenic and polygenic causes of obesity. The genetics of obesity could be classified into syndromic and non-syndromic obesity. Prader–Willi, fragile X, Bardet–Biedl, Cohen, and Albright Hereditary Osteodystrophy (AHO) syndromes are examples of syndromic obesity, which are associated with developmental delay and early onset obesity. Non-syndromic obesity could be monogenic, polygenic, or chromosomal in origin. Monogenic obesity is caused by variants of single genes while polygenic obesity includes several genes with the involvement of members of gene families. New advances in genetic testing have led to the identification of obesity-related genes. Leptin (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), the melanocortin 4 receptor (MC4R), single-minded homolog 1 (SIM1), brain-derived neurotrophic factor (BDNF), and the neurotrophic tyrosine kinase receptor type 2 gene (NTRK2) have been reported as causative genes for obesity. NGS is now in use and emerging as a useful tool to search for candidate genes for obesity in clinical settings.

Prader-Willi syndrome (PWS) is caused by a deficiency of imprinted genes in the 15q11-q13 region and is characterized by prenatal onset of hypotonia, poor feeding, childhood-onset obesity, hyperphagia, short stature, facial dysmorphism, intellectual disability, and behavioral problems. We studied perinatal factors in a cohort of 64 people with PWS resulting from paternal deletion of 15q11-q13 and maternal uniparental disomy (UPD) for chromosome 15. We recruited 34 individuals with deletion and 30 with UPD. We compared the frequency of multiple prenatal and neonatal factors with the general population as well as between the two genetic subtypes. Of the 64 individuals with PWS, fetal movements were decreased in 82.8%, 31.7% were born prematurely, 42.1% by Cesarean section, and 35.9% required oxytocin induction. Apgar scores were low in 34.6%, 96.8% had feeding difficulty, 50% needed tube feeding, and 6.2% subsequently had gastrostomy tube placement. On comparing findings in the deletion versus the UPD groups, we did not find many significant differences. We, however, found a higher maternal age, and also later age at diagnosis in the UPD versus the deletion group. PWS subjects have higher rates of perinatal complications, especially Cesarean section rate, hypotonia, and low Apgar scores compared to the general population. We did not find many differences between the genetic subtypes, except for later age of diagnosis of the UPD 15 group suggesting a milder phenotype. We also found that the mothers in the UPD were older, supporting the hypothesis that UPD results from nondisjunction associated trisomy rescue.