Penetrance

Penetrance is 100%. All individuals with germline pathogenic variants in SYNGAP1 have developmental delay, cognitive dysfunction, intellectual disability, and/or epilepsy.

Source: GeneReviews — "SYNGAP1-Related Intellectual Disability"

Diagnostic Criteria

No formal diagnostic criteria have been published for SYNGAP1-related intellectual disability.

Suggestive Findings

SYNGAP1-related intellectual disability (SYNGAP1-ID) should be considered in individuals with developmental delay or intellectual disability with or without:

• Generalized epilepsy;

and/or

• Autism spectrum disorder (ASD).

Establishing the Diagnosis

The diagnosis of SYNGAP1-ID is established in a proband with developmental delay (DD) or intellectual disability (ID) in whom molecular genetic testing identifies either:

• A heterozygous pathogenic (or likely pathogenic) variant in SYNGAP1 (~89%);

or

• A deletion of 6p21.3 (~11%).

Source: GeneReviews — "SYNGAP1-Related Intellectual Disability"

Differential Diagnosis

The phenotype associated with SYNGAP1-related intellectual disability (ID) overlaps with that of other disorders of ID and epileptic encephalopathy. Most genes known to be associated with ID (see OMIM Autosomal Dominant Intellectual Developmental Disorder Phenotypic Series) and epileptic encephalopathy (see OMIM Epileptic Encephalopathy, Early Infantile Phenotypic Series) if compatible with walking should be included in the differential diagnosis.

Source: GeneReviews — "SYNGAP1-Related Intellectual Disability"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with SYNGAP1-related intellectual disability, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 2. Recommended Evaluations Following Initial Diagnosis in Individuals with SYNGAP1-Related Intellectual Disability

Source: GeneReviews — "SYNGAP1-Related Intellectual Disability"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. Search CURE ID (an FDA website) for information on novel uses of existing drugs for this condition (SYNGAP1 Overview). Note: Any off-label use of drugs should be done at the discretion of the treating physician in conjunction with the affected individual and/or their caregiver and is not endorsed by GeneReviews or the authors of this chapter.

Source: GeneReviews — "SYNGAP1-Related Intellectual Disability"

Surveillance Guidelines

Monitor those with seizures as clinically indicated. Assess as needed for anxiety, attention, and aggressive or self-injurious behavior. Monitor developmental progress and educational needs.

Source: GeneReviews — "SYNGAP1-Related Intellectual Disability"