(MRD8)

Very rare: < 1/106.  De novo mutation of the GRIN1 gene (Glutamate Receptor Ionotropic N-Methyl D Aspartate type 1) (9q) causing NMDA receptor dysfunction. This glutaminergic receptor plays an important role in synaptogenesis, excitotoxicity and synaptic plasticity in the central nervous system. It is composed of 7 subunits coded by different genes: one GluN1 by GRIN1, four GluN2 by GRIN2A-D and two GluN3 coded for by GRIN3A-B. These subunits are grouped into heterogeneous tetrameric complexes composed of 2 GluN1 subunits and two units composed of GluN2 and or GluN3.

Clinical presentation: variable combination of

-        epileptogenic encephalopathy (early onset <3 months of age) (50 %): the type of epilepsy is very variable

-        hyperkinetic movements (50 %)

-        abnormal eye movements (similar to an oculogyria crisis)

-        stereotypic hand movements,

-        severe developmental delay,

-        intellectual deficit

MRI: non-specific images: ventriculomegaly, thin corpus callosum, cerebral atrophy

Anesthetic implications:

severe epilepsy, growth retardation

References :

-        Ohba C, Shiina M, Tohyama J, Haginoya K, Lerman-Sagie T et al.
GRIN1 mutations cause enceephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.
Epilepsia 2015; 56:841-8.

-        Zehavi Y, Mandel H, Zehavi A, Abu Rashid M, Straussberg R, Jabur B, Shaag A, Elpeleg O, Spiegel R.
De novo GRIN1 mutations: an emerging cause of severe infantile encephalopathy.
Eur J Med Genetics 2017; 60:317-20

Updated: June 2022