Infantile choreatic movements, early onset severe epileptic encephalopathy, and primary developmental impairment as a result of a de novo missense mutation in the SCN2A gene

Introduction: We report a 4-year-old patient with a severe early onset intractable epileptic encephalopathy, primary global developmental impairment, secondary microcephaly, and distinct choreatic movements in infancy.

Case: The 5-month-old patient was referred to our clinic for investigation of abnormal eye movements suspicious for seizures. Early development was delayed and parents reported excessive sleeping time over the day. The girl presented with hypotonia, apathy, peculiar choreoathetotic movements predominantly of the upper extremities, and lack of visual contact. Head growth decreased during the first 6 months. Infantile spasms and myoclonic seizures were observed and the EEG revealed hypsarrhythmia. Seizures were refractory to several anticonvulsive drugs, only during treatment with corticosteroids, the patient became seizure free. The choreatic movements subsided at the age of 12 months. However, impressive hypersomnia and severe motor and cognitive impairment persisted. Cranial MRI at the age 5 months showed a cortical and subcortical atrophy, MR spectroscopy was normal. The metabolic workup, chromosome analysis, and microarray CGH showed no abnormal findings. Clinical and genetic reevaluation at the age of 4 years revealed a heterozygous missense mutation in the SCN2A gene.

Conclusions: The SCN2A gene encodes one of four subunits of voltage-gated sodium channels, which are the major mediators of normal cerebral neuronal firing. Mutations in the SCN2A gene have been reported in patients with benign familial neonatal infantile seizures (BFNIS), generalized epilepsy with febrile seizures plus (GEFS+), and severe myoclonic epilepsy in infancy (SMEI). In the past 10 years, the phenotypical spectrum of SCN2A mutations has expanded. To our best knowledge, our patient is the first reported child with severe early onset epileptic encephalopathy, distinct choreatic movements, and severe developmental impairment as a result of a de novo missense mutation in the SCN2A gene. Our case illustrates a more diversified phenotypical spectrum of SCN2A mutations than previously assumed.