Interventions targeting challenges experienced by individuals with Pitt Hopkins syndrome: a scoping review

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder with pronounced impacts on physical health and everyday functioning, including severe intellectual disability, impaired communication, epilepsy, and breathing dysregulation. Despite significant clinical challenges, there is limited evidence to guide interventions for individuals with PTHS. This scoping review aimed to examine the available literature on interventions targeting challenges experienced by individuals with PTHS and to identify gaps in the current knowledge base.

Sixteen peer-reviewed publications, published between 2012 and 2024, met the inclusion criteria. The majority of studies focused on medical management, predominantly addressing epilepsy and breathing abnormalities, and were pharmacological in nature. Most studies employed case report or small case series designs, and systematic outcome measurement approaches were rare. Epilepsy interventions largely reflected clinical practices in broader epilepsy populations, with common use of conventional antiseizure medications and evidence of potential benefit from newer agents in treatment-resistant cases. Non-pharmacological treatments, including vagus nerve stimulation, corpus callosotomy, ketogenic diet, and a walking-based mobility intervention, were described in only a few studies, with heterogeneous outcomes. Interventions for respiratory dysfunction, gastrointestinal symptoms, pain management, immune dysfunction, psychiatric or behavioral difficulties were limited and typically reported in individual cases. Research addressing psychosocial, behavioral, and participation-focused interventions was notably scarce, despite the broad functional impairments associated with PTHS.

This scoping review shows that intervention research in PTHS remains at an early stage, with an evidence base dominated by descriptive case studies and few systematic evaluations. This limits the ability to formulate robust, evidence-based treatment recommendations. There is a need for more rigorous research designs in future research, that enable causal inference and systematic outcome measurement. Moreover, future studies should broaden the scope of intervention research to include communication, behavior, participation, physical activity and quality of life, alongside medical management, to better support the complex needs of individuals with PTHS. Increased focus on family impact and long-term outcomes may further enhance understanding and care strategies for this population.