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SYNGAP1-related intellectual disability
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

SYNGAP1-related intellectual disability

SYNGAP1-related intellectual disability is a neurological disorder marked by moderate to severe intellectual disability, early speech and motor delays, and frequent epilepsy. It results from mutations in the SYNGAP1 gene that disrupt synaptic development.

Overview

SYNGAP1-related intellectual disability is a neurological disorder characterized by moderate to severe intellectual disability that is evident in early childhood. The earliest features are typically delayed development of speech and motor skills, such as sitting, standing, and walking. Many people with this condition have weak muscle tone (hypotonia), which contributes to the difficulty with motor skills. Some affected individuals lose skills they had already acquired (developmental regression). Other features of SYNGAP1-related intellectual disability include recurrent seizures (epilepsy), hyperactivity, and autism spectrum disorder, which is characterized by impaired communication and social interaction; almost everyone with SYNGAP1-related intellectual disability develops epilepsy, and about half have autism spectrum disorder.

Frequency

SYNGAP1-related intellectual disability is a relatively common form of cognitive impairment. It is estimated to account for 1 to 2 percent of intellectual disability cases.

Causes

SYNGAP1-related intellectual disability is caused by mutations in the SYNGAP1 gene. The protein produced from this gene, called SynGAP, plays an important role in nerve cells in the brain. It is found at the junctions between nerve cells () and helps regulate changes in synapses that are critical for learning and memory. Mutations involved in this condition prevent the production of functional SynGAP protein from one copy of the gene, reducing the protein's activity in cells. Studies show that a reduction of SynGAP activity can have multiple effects in nerve cells, including pushing synapses to develop too early. The resulting abnormalities disrupt the synaptic changes in the brain that underlie learning and memory, leading to cognitive impairment and other neurological problems characteristic of SYNGAP1-related intellectual disability.

Learn more about the gene associated with SYNGAP1-related intellectual disability

  • SYNGAP1

Inheritance

SYNGAP1-related intellectual disability is classified as an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all cases result from and occur in people with no history of the disorder in their family. In at least one case, an affected person inherited the mutation from .

Other Names for This Condition

  • Mental retardation, autosomal dominant 5
  • MRD5

Additional Information & Resources

Genetic Testing Information

  • Genetic Testing Registry: Intellectual disability, autosomal dominant 5

Genetic and Rare Diseases Information Center

  • Intellectual developmental disorder, autosomal dominant 5

Patient Support and Advocacy Resources

  • National Organization for Rare Disorders (NORD)

Clinical Trials

  • ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

  • INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5; MRD5

Scientific Articles on PubMed

  • PubMed

References

  • Aceti M, Creson TK, Vaissiere T, Rojas C, Huang WC, Wang YX, Petralia RS, Page DT, Miller CA, Rumbaugh G. Syngap1 haploinsufficiency damages a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly. Biol Psychiatry. 2015 May 1;77(9):805-15. doi: 10.1016/j.biopsych.2014.08.001. Epub 2014 Aug 13. Citation on PubMed or Free article on PubMed Central
  • Clement JP, Aceti M, Creson TK, Ozkan ED, Shi Y, Reish NJ, Almonte AG, Miller BH, Wiltgen BJ, Miller CA, Xu X, Rumbaugh G. Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses. Cell. 2012 Nov 9;151(4):709-723. doi: 10.1016/j.cell.2012.08.045. Citation on PubMed or Free article on PubMed Central
  • Clement JP, Ozkan ED, Aceti M, Miller CA, Rumbaugh G. SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity. J Neurosci. 2013 Jun 19;33(25):10447-52. doi: 10.1523/JNEUROSCI.0765-13.2013. Citation on PubMed or Free article on PubMed Central
  • Mignot C, von Stulpnagel C, Nava C, Ville D, Sanlaville D, Lesca G, Rastetter A, Gachet B, Marie Y, Korenke GC, Borggraefe I, Hoffmann-Zacharska D, Szcz

Frequently Asked Questions

Behavioral interventions such as applied behavior analysis (ABA), visual schedules, and social skills groups are first‑line and can reduce anxiety and improve routine adherence. If hyperactivity or aggression is severe, a pediatric psychiatrist may consider low‑dose stimulants (e.g., methylphenidate) or atypical antipsychotics (e.g., risperidone) after a careful risk‑benefit discussion, as some children with SYNGAP1 respond well to these medications.
Early intensive speech‑language therapy combined with augmentative and alternative communication (AAC) systems (e.g., picture exchange or speech‑generating devices) can boost expressive language. For motor delays, a structured physical therapy program focusing on strength, balance, and gait training—often delivered several times per week—has shown benefit, especially when started before age three.
Seizures often begin in the first two years of life and may start as brief staring spells, subtle facial twitching, or sudden stiffening of the arms and legs. Parents should keep a seizure diary noting the duration, triggers, and any post‑ictal confusion, and contact the pediatric neurologist promptly for EEG evaluation and possible antiepileptic medication adjustments.
Because SYNGAP1 mutations are typically de novo (new in the child), the recurrence risk for siblings is low (<1 %). However, targeted genetic testing (sequencing of the known variant) can be offered to siblings to rule out mosaicism. For future pregnancies, prenatal testing or pre‑implantation genetic diagnosis is possible if the specific mutation is known, but counseling with a medical geneticist is recommended to discuss the low recurrence risk and testing options.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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