Updated consensus guidelines on the management of Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

Bringing everyone to the table - findings from the 2018 Phelan-McDermid Syndrome Foundation International Conference.

BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare neurodevelopmental disorder characterized by global developmental delay, autism spectrum disorder, and numerous systemic complications including seizures, gastrointestinal dysfunction, and renal anomalies. The Phelan-McDermid Syndrome Foundation (PMSF) was created to improve the quality of life of people affected by PMS worldwide by supporting families, accelerating research, and raising awareness. To further this mission, the PMSF initiated the Phelan-McPosium in 2016 to bring families affected by PMS, clinicians, and researchers together to design patient-centered rigorous clinical and translational research. Here, we present findings from the 2018 Phelan-McPosium. RESULTS: The 2018 Phelan-McPosium was attended by 183 families and 35 researchers and clinicians. Overall, the Early Childhood parents raised the fewest number of concerns, families of Late-Childhood patients raised more concerns around epilepsy and behavioral problems, and Teen and Adult families were primarily concerned about implications of genetic testing, gastrointestinal dysfunction, and regression. All families were concerned with feasibility, safety and importance of clinical trials for PMS. CONCLUSIONS: The concerns raised by families across the sessions varied by age in a manner which may overlap with the emergence of various signs and symptoms through the natural history of PMS. The design of the Phelan-McPosium session has successfully generated thoughtful research questions that led to innovative investigations and clinical trials that are shaping the standard of care for PMS. This is an approach which could be employed by any rare disease group to align translational research efforts with a patient-centered focus.