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GRIN1 encodes the obligate subunit (GluN1) of glutamate N-methyl-d-aspartate receptor (NMDAr). Pathogenic variants in GRIN1 are a well-known cause of infantile encephalopathy characterized by profound developmental delay (DD), variable epileptic phenotypes, and distinctive behavioral abnormalities. Recently, GRIN1 has also been implicated in the pathogenesis of polymicrogyria (PMG).

We investigated two patients presenting with severe intellectual disability (ID), epilepsy, stereotyped movements, and abnormal ocular movements. They showed distinctive circadian rhythm alterations and sleep-wake patterns anomalies characterized by recurrent cyclic crying or laughing spells. Genetic analysis led to the identification of two distinct de novo variants in GRIN1 affecting the same amino acid residue of an important functional protein domain.

Recent advances in circadian rhythm and sleep regulation suggest …