GRIN2A-related disorder causes profound developmental delay and a disorder affecting movement

Although GRIN2A-related disorders are associated with childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, continuous spike and wave during slow wave sleep, atypical rolandic epilepsy, and speech impairment, the clinical spectrum of these disorders is broad. We report a patient with GRIN2A-related disorder with profound developmental delay and predominantly involuntary movement. The patient had been vomiting frequently because of gastric volvulus. He exhibited daily paroxysmal involuntary movements and abnormal eye movements from 2 months of age. The abnormal eye movements were often asymmetrical and resembled oculogyric crisis. To rule out inherited monoamine neurotransmitter disorders, neurotransmitter levels in the cerebrospinal fluid were measured, which showed approximately normal results. Currently, the patient suffers from profound psychomotor developmental delay, is nonverbal and non-ambulatory, lacks independent head control, and is bedridden. Whole exome sequencing revealed a de novo heterozygous missense variant (NM_001134407.3:c.1904C > T, p.(Ala635Val)) in the GRIN2A gene. A missense variant of GRIN2A caused profound developmental delay and a disorder predominantly affecting movement. The patient's phenotype was very severe and was similar to that of an inherited monoamine neurotransmitter disorder. GRIN2A-related disorders should be considered in patients with suspected inherited monoamine neurotransmitter disorders.