Clinical Characteristics

Individuals with GRIN2D-related neurodevelopmental disorder have been reported less frequently than individuals with other GRIN-related disorders. All affected individuals known so far have moderate-to-severe DD/ID. Epilepsy is seen in nearly all affected individuals showing severe, early-onset, medically refractory epileptic encephalopathy (including spasms with hypsarrhythmia). Additional features are muscular hypotonia, spasticity, feeding difficulties and movement disorders.

Clinical variability
GRIN2D-related neurodevelopmental disorder is mostly severe. Penetrance of GRIN2D-related neurodevelopmental disorder is thought to be 100%.

Differential diagnosis
It can be difficult to differentiate individuals with GRIN2D-related neurodevelopmental disorder from similar disorders caused by pathogenic variants in neurodevelopmental disorder related genes. Genetic testing confirming the identification of a pathogenic variant in GRIN2D is therefore the only reliable test confirming the diagnosis. All genes known to be associated with ID and early-onset epileptic encephalopathy should be included in the differential diagnosis of GRIN2D-related neurodevelopmental disorder.