SYNGAP1-Related Disorder
What is SYNGAP1-related disorder?
SYNGAP1-related disorder is a rare genetic neurodevelopmental disorder caused by a pathogenic variant in the SYNGAP1 gene. It is also referred to as SYNGAP1-related intellectual disability (SYNGAP1-ID) or SYNGAP1-related developmental and epileptic encephalopathy.
The SYNGAP1 gene provides instructions for making SynGAP, a protein that plays an important role in communication between brain cells and in normal brain development. Changes affecting this gene can disrupt neuronal signaling and development.
The condition commonly affects development, learning, communication, behavior, and seizure control. The severity and combination of symptoms can vary considerably from one individual to another.
Common features
People with SYNGAP1-related disorder may experience:
- Developmental delay and intellectual disability
- Epilepsy or recurrent seizures
- Speech and language delay or absence of speech
- Motor-development difficulties, including delayed walking and hypotonia
- Learning difficulties
- Autism spectrum features or other behavioral differences
- Sleep difficulties
- Feeding and eating difficulties
- Sensory processing differences
- Movement and coordination difficulties
- Gastrointestinal problems such as constipation
- Orthopedic problems, including hip abnormalities, scoliosis or flat feet
- Vision problems such as strabismus
Epilepsy is particularly common. GeneReviews reports generalized epilepsy in approximately 84% of affected individuals, with some individuals experiencing myoclonic-atonic (myoclonic-astatic/Doose syndrome) epilepsy or other generalized seizure types.
How is SYNGAP1-related disorder diagnosed?
Diagnosis is established through genetic testing that identifies a pathogenic or likely pathogenic variant affecting SYNGAP1, or in some cases a deletion involving the relevant chromosomal region.
Children with unexplained developmental delay, intellectual disability and/or epilepsy may undergo genetic investigations such as chromosomal microarray, epilepsy/intellectual-disability gene panels or whole-exome/genome sequencing.
A genetic diagnosis can help families understand the cause of their child’s condition and can also guide appropriate medical, developmental and supportive care.
Why does SYNGAP1 happen?
SYNGAP1-related disorder is generally caused by a de novo genetic variant, meaning that the change occurs in the child and is not inherited from either parent.
It follows an autosomal dominant pattern. Rarely, parental mosaicism or other inheritance circumstances can affect recurrence risk, so genetic counselling is recommended for families.
Treatment and management
There is currently no established disease-modifying treatment that cures SYNGAP1-related disorder. Management focuses on controlling seizures and supporting the individual’s development, communication, learning, behavior, mobility, feeding and overall quality of life.
Depending on the individual’s needs, care may involve:
- Pediatric neurology and epilepsy management
- Developmental pediatrics
- Genetic counselling
- Physiotherapy
- Occupational therapy
- Speech and language therapy
- Feeding and swallowing therapy
- Behavioral and developmental interventions
- Special education and learning support
- Ophthalmology
- Gastroenterology
- Orthopedic care
- Psychological and family support
There is currently no single anti-seizure medication recommended specifically for SYNGAP1. Treatment is individualized according to seizure type and clinical response.
Importance of early diagnosis
Because SYNGAP1-related disorder can present with a combination of developmental delay, epilepsy, speech difficulties and behavioral or autism-related features, diagnosis may sometimes be delayed.
Early genetic diagnosis can help families access:
- Appropriate specialist care
- Developmental and rehabilitative therapies
- Genetic counselling
- Educational support
- Disease-specific information
- Patient and caregiver support networks
- Research and clinical-trial opportunities
SYNGAP1 and research
SYNGAP1 is an active area of rare-disease research. Researchers and biotechnology companies are investigating potential gene-targeted and RNA-based approaches, including strategies intended to increase functional SYNGAP1 protein.
Because SYNGAP1 is a haploinsufficiency disorder, increasing expression from the functional copy of the gene is one of the therapeutic strategies being investigated.
Clinical research and therapeutic development are ongoing, and families should discuss participation in research or clinical trials with their treating physician and research teams.
SYNGAP1 in India
SYNGAP1-related disorder remains under-recognized, and the number of diagnosed individuals in India is likely to represent only a portion of the actual affected population.
Greater awareness among pediatricians, pediatric neurologists, developmental pediatricians, geneticists and rehabilitation professionals may help identify more children who could benefit from genetic testing.
Building a SYNGAP1 patient and caregiver community in India can help families connect with one another, improve awareness, support data collection and patient registries, facilitate access to information and research opportunities, and provide a collective voice for the needs of affected individuals and their families.
There is currently an active community of 7 diagnosed SYNGAP1 patients and their families in India, connected through SYNGAP1 India, which is part of the CureSYNGAP1 Collective, an international SYNGAP1 patient and caregiver community.
The group aims to bring families affected by SYNGAP1 together, improve awareness of the disorder, facilitate access to information and resources, encourage collaboration with healthcare professionals and researchers, and help families connect with others going through similar experiences.
As SYNGAP1 is a rare and underdiagnosed condition, connecting with other families can be particularly valuable for newly diagnosed individuals and their caregivers.
If you or your child has been diagnosed with SYNGAP1-related disorder and would like to connect with other families in India, you can contact: Amit Mandora
Or
ORDI can facilitate the connection with the existing SYNGAP1 India patient and caregiver community.
Families are encouraged to reach out to connect with the SYNGAP1 India community and learn more about available support, resources, research opportunities and ongoing initiatives.
Important: This information is intended for educational and awareness purposes and should not replace individualized medical advice from qualified healthcare professionals.
