2025 DESSH Symposium Presentations

Dr. Marwan Shinawi, pediatric geneticist, provides an overview of DeSanto-Shinawi (DESSH) syndrome, including its clinical features and genetic causes. Dr. Shinawi highlights data on cognitive and physical characteristics, diagnostic approaches, and the importance of large-scale natural history studies to advance understanding of the disorder.

Dr. Weisenberg, pediatric neurologist, presents an overview of neurologic features in DESSH syndrome, including hypotonia, developmental delays, apraxia, and MRI findings, emphasizing the value of interdisciplinary management and realistic expectations for developmental progress. She cites the importance of sleep-cycle EEGs for accurate assessment.

Dr. Glazer presented strategies for managing behavioral and psychiatric challenges in children with DESSH syndrome, including OCD, ADHD, anxiety, and aggression. He emphasized that behaviors can serve as a form of communication and recommended a combination of behavioral therapies, parent training, and, in some cases, medication. The presentation also highlights the importance of early language and social skill development, structured environments, and consistent routines to support independence and long-term outcomes.

Dr. Amarikian's presentation focuses on constipation, gastroesophageal reflux, and feeding difficulties. She discusses medical and surgical treatment options, and emphasizes a multidisciplinary approach involving speech therapy, occupational therapy, and dietitian support. The session also addressed practical management questions, such as handling constipation related to ADHD medications.

Erin McRoy, a genetic counselor, presented on genetic reporting for DESSH. She explained the basics of genetics, different types of genetic tests, and components of genetic reports, including variant classification (benign, likely benign, variant of unknown significance, likely pathogenic, or pathogenic). Erin discussed inheritance patterns, particularly autosomal dominant transmission, and addressed questions about de novo mutations and germline mosaicism.

Dr. Gabel presented a roadmap for developing therapies for DESSH Syndrome, highlighting how basic research informs understanding of the underlying biology and guides potential treatments. He discussed two main approaches: repurposing existing drugs for symptom management and designing therapies that target the root cause, including gene-based strategies. The session emphasized the importance of patient data collection through registries like RARE-X to establish outcome measures for clinical trials and addressed opportunities and challenges in developing treatments for rare disorders.

Drs. Thompson and Lambert highlighted the Baby Force program, an innovative approach using AI-driven drug repurposing to treat ultra-rare genetic conditions in neonates. The doctors presented the case of Jorie, a patient with DESSH Syndrome, detailing how a potential therapeutic was identified, tested in fibroblasts, and led to clinical improvements in development and airway function.