ESPE Abstracts

Background/aims: Prader-Willi syndrome (PWS) is a rare genetic syndrome, caused by the loss of expression of the paternal chromosome 15q11-q13 region. Over the past years, many cases of patients with characteristics similar to PWS, but without the typical genetic aberration of the 15q11-q13 region, have been described. These patients are often labelled as Prader-Willi-like (PWL). PWL is an as-yet poorly defined syndrome, potentially affecting a significant number of children and adults. In the current clinical practice, patients labelled as PWL are mostly left without treatment options. Considering the similarities with PWS, children with PWL might benefit from the same multidisciplinary care and treatment as children with PWS. In order to gain more knowledge on PWL, we performed a literature study with the aim of providing a complete overview of published cases of patients with the PWL phenotype.

Methods: We conducted a Pubmed Search to identify papers published between January 1963 to May 2020 using the keywords overweight/obesity and intellectual disability. This lead to inclusion of 86 papers for review. Data extraction focused on clinical features related to PWS, distinguishing clinical features and the genetic diagnosis.

Results: Overall, 368 individual cases with 35 distinct genetic diagnoses were included. The most common genetic diagnoses were Temple syndrome (formerly known as maternal uniparental disomy 14), Schaaf-Yang syndrome (truncating mutation in the MAGEL2 gene), 1p36 deletion, 2p deletion, 6q deletion, 6q duplication, 15q deletion,15q duplication, 19p deletion, fragile X syndrome and Xq duplication. The most prevalent symptoms in the entire group were developmental delay/intellectual disability (76%), speech problems (64%), overweight/obesity (57%), hypotonia (56%) and psycho-behavioral problems (53%).

Conclusion: We describe mutations and aberrations for consideration when suspicion of PWS remains after negative testing and summarize the characteristics most prevalent in possible PWL conditions. In addition we propose a diagnostic approach to patients with a PWL phenotype for (pediatric) endocrinologists. PWL comprises a complex and diverse group of patients, which calls for multidisciplinary care with an individualized approach.