DeSanto-Shinawi syndrome

DeSanto-Shinawi Syndrome (DSS), also known as SHANK3-related intellectual disability syndrome, is a rare genetic disorder characterized by a range of physical, developmental, and neurological abnormalities. First described by DeSanto and Shinawi in a 2010 study, the syndrome is caused by mutations in the SHANK3 gene located on chromosome 22q13.3. This gene plays a crucial role in the development and function of neural synapses, affecting cognitive, social, and motor skills.

Symptoms and Diagnosis

The clinical presentation of DeSanto-Shinawi Syndrome can vary significantly among affected individuals. Common symptoms include mild to moderate intellectual disability, speech delay and other communication challenges, hypotonia (decreased muscle tone), and behavioral issues such as anxiety, ADHD (Attention Deficit Hyperactivity Disorder), and autism spectrum disorder-like behaviors.

Physical features may include distinct facial characteristics such as wide-set eyes, a broad nasal tip, and a thin upper lip. Some individuals may also exhibit feeding difficulties, growth delays, and skeletal anomalies such as scoliosis.

Diagnosis of DSS is primarily based on genetic testing, which can identify mutations in the SHANK3 gene. Clinical evaluations, including developmental assessments and neurological examinations, support the diagnosis and help in the management of the syndrome.

Management and Treatment

There is no cure for DeSanto-Shinawi Syndrome, and treatment is symptomatic and supportive. Management strategies may include:

• Speech therapy and occupational therapy to improve communication and daily living skills.
• Physical therapy to address hypotonia and motor skill delays.
• Behavioral therapies to manage autism spectrum disorder-like symptoms and ADHD.
• Medications may be prescribed to treat anxiety, ADHD, or other co-occurring conditions.

Early intervention and a multidisciplinary approach are crucial for improving the quality of life of individuals with DSS.

Genetics

DeSanto-Shinawi Syndrome is caused by mutations in the SHANK3 gene, which encodes a protein involved in synaptic formation and function in the brain. The syndrome is inherited in an autosomal dominant pattern, meaning a mutation in just one of the two copies of the gene is sufficient to cause the disorder. However, many cases result from de novo mutations, which occur spontaneously and are not inherited from the parents.

Research and Outlook

Ongoing research aims to better understand the pathophysiology of DeSanto-Shinawi Syndrome and to explore potential therapeutic strategies. Advances in genetic therapies and neurodevelopmental research hold promise for future treatments.

As awareness and understanding of DSS increase, early diagnosis and intervention strategies continue to improve, offering hope for affected individuals and their families.