[MIM 603 384]

It could be the cause of about 1 to 2 % of cases of intellectual disability from genetic origin. De novo mutation of the SYNGAP1 gene (6p21.32) codingfor the synaptic Ras GTPase Activating Protein 1 (SYNGAP1). This protein acts as a regulator in excitatory neuronal synapses at the GluN2B sub-unit of the NMDA-like glutamatergic receptors. It is mainly localized in the dendrites of neurons in the pyramidal pathways of the neocortex where it suppresses signals related to NMDA (synaptic plasticity) and AMPA receptors. Mutations lead to a decrease or absence of protein production, and an increase in synaptic excitability.

The clinical presentation is very variable:

1.        intellectual disability (mild to severe): in particular, autosomal dominant non-syndromic intellectual disability type 5

2.        hypotonia

3        global development delays

4.        epilepsy including epileptic and developmental encephalopathy associated with SYNGAP1  and Doose syndrome (myoclo-astatic epilepsy)

5.        sensory disorders

6.        delays in gross and fine motor skills

7.        dyspraxia (coordination disorder)

8.        speech delays (moderate to severe: many children are non-verbal)

9.        autism

10.        sleep and behavioral disorders

Anesthetic implications:

epilepsy, developmental delay, behavioral disorders

References :

-        Okazaki T, Saito Y, Hiraiwa R, Saitoh S, Kai M, Adachi K, Nishimura Y et al.
Pharmacoresistant epileptic eyelid twitching in a child with a mutation in SYNGAP1.
Epileptic Disorders. 2017;19 :339-44.

Update: November 2021