DeSanto-Shinawi syndrome due to WAC point mutation

DeSanto-Shinawi syndrome due to WAC point mutation is a neurodevelopmental disorder that primarily affects early childhood development. The condition is caused by pathogenic variants in the WAC gene, which plays an important role in cellular processes that influence brain development. Children with this syndrome typically present with global developmental delay and atypical behavior, among other challenges, and the impact on cognitive and neurological functions is a major concern for families. This condition is very rare, affecting fewer than 1 in 1 million people, and its rarity adds to the diagnostic challenges and the need for individualized care.

The clinical features of DeSanto-Shinawi syndrome reflect its impact on neurodevelopment as well as other body systems. Almost all affected individuals exhibit global developmental delay, which can affect cognitive, intellectual, and social skills from an early age. Atypical behavior is also commonly observed, with many families reporting challenges related to learning and adaptive functioning. In addition, a majority of individuals experience constipation, and a significant proportion may have seizures, feeding difficulties, and sleep disturbances. More variable findings include sensorineural hearing impairment and hypoplasia of the corpus callosum, which may influence communication and overall neurological function. That not all individuals experience every feature and that severity varies considerably between persons.

DeSanto-Shinawi syndrome is caused by a point mutation in the WAC gene, a gene integral to several cellular pathways that influence brain development and function. The condition is inherited in an autosomal dominant manner, meaning that a single altered copy of the gene is sufficient to affect development. In many cases, the mutation arises as a new (de novo) event, which means that there is typically no family history of the condition. However, when a pathogenic variant is present in a parent, there is a potential risk of transmission to future offspring. Given the complexities of genetic inheritance and the fact that the presentation can vary widely among affected individuals, genetic counseling is highly recommended for families considering future pregnancies or seeking a deeper understanding of the genetic implications.

Currently, management of DeSanto-Shinawi syndrome focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. Care is tailored to the individual and typically involves a multidisciplinary approach that includes developmental pediatrics, neurology, behavioral therapy, and educational support. Regular surveillance is an essential part of long-term management, helping to monitor developmental progress, address feeding or sleep difficulties, and manage gastrointestinal issues such as constipation. Although no foundational therapies have been established, individualized interventions such as speech therapy, occupational therapy, and physical therapy may provide significant benefits and improve overall quality of life. In all cases, patients are encouraged to discuss treatment options with their healthcare team to determine the most appropriate strategies for their unique needs, and genetic counseling is recommended to further guide families.

The long-term outlook for individuals with DeSanto-Shinawi syndrome is highly variable, with significant differences observed in the severity and combination of symptoms among affected persons. As a lifelong neurodevelopmental condition, children with the syndrome may face ongoing challenges related to cognitive and behavioral development, although many individuals benefit from interventions designed to support learning and communication. Outcomes described in medical literature continue to evolve as standards of care improve and as more is learned about the condition through clinical experiences and research. Families are encouraged to seek support from specialist care providers and genetic counselors, and to connect with patient advocacy groups, as these resources can be invaluable in navigating the complexities of living with the condition.

There is ongoing research into potential treatment options for DeSanto-Shinawi syndrome, with clinical trials currently underway exploring new approaches for management. Although there is only one clinical trial active at this time, research into the underlying mechanisms of the condition and strategies to improve developmental outcomes is an active area of investigation. Individuals interested in learning more about or participating in clinical trials should consult ClinicalTrials.gov or speak with their care team about eligibility and current research opportunities.