Framework for assessing individuals with rare genetic disorders associated with profound intellectual and multiple disabilities (PIMD): the example of Phelan McDermid Syndrome

Abstract

Background: Specialized strategies are needed to understand the complex neuropsychological impairments reported in individuals with profound intellectual and multiple disabilities (PIMD) associated with rare genetic disorders. Methods: This narrative review focuses on assessment of individuals with Phelan-McDermid Syndrome (PMS) as a condition commonly associated with PIMD. Published case series and prospective studies were reviewed to evaluate approaches to cognitive, language, motor/sensory, and behavioral domains. This review is framed using general principles for neuropsychological evaluation in PIMD. Results: Neuropsychological assessment domains and tools varied across published reports. Adaptive behavior measures, out-of-range developmental assessments, and social-communication measures were commonly used. Available findings were used to shape a recommended framework with potential to improve measurement of clinical outcomes and advance scientific discovery. Conclusions: The recommended framework outlines an inter-disciplinary and multimodal neuropsychological assessment process relying on modified standardized assessments, functional assessments, and caregiver/informant reports when evaluating individuals with PIMD. Arrested development and skill variability/regression are also discussed as additional, important considerations in neuropsychological evaluation of individuals with PIMD and rare genetic disorders.

Keywords:

• Intellectual disability
• Phelan-McDermid Syndrome
• neuropsychological assessment
• cognition

Acknowledgements

We would like to thank Cristan Farmer for her contribution to this manuscript. We would also like to thank the Developmental Synaptopathies Consortium (U54NS092090), part of NCATS Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Disease Research (ORDR). This consortium is funded through collaboration between NCATS, and the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Notes

1. Several terms have been used to describe this population. In addition to PMID, PMLD has also been used, and refers to Profound and Multiple Learning Disabilities.