A novel splicing SCN2A mutation in an adolescent with low functioning autism, acute dystonic movement disorder and late-onset generalized epilepsy

Pathogenic variants in SCN2A have been associated to a wide spectrum of neurodevelopmental disorders, including developmental and epileptic encephalopathy (DEE), self-limited familial neonatal-infantile epilepsy (SeLFNIE), autism spectrum disorder (ASD) and intellectual disability (ID) with and without epilepsy ([1]. Movement disorders as dystonia, dyskinesia, choreoathetosis, opisthotonos, and oculogyric crisis are described in about 11% - 84% of patients with SCN2A mutations ([2] Here, we describe a 14-years old African girl with low-functioning ASD who developed an acute dystonic movement disorder and late-onset generalized seizures, carrying a de novo splicing mutation in SCN2A gene. The patient was born by non-consanguineous Nigerian parents at 39 weeks of gestation after uncomplicated pregnancy. At age of 3 years, ASD was diagnosed. Karyotype and molecular test for Rett, Angelman and X-fragile syndromes were negative. Brain MRI and sleep EEG were both negative. To control psychomotor agitation, risperidone was introduced at 10 years of age. At age of 14 years, she started to develop segmental cervical dystonias, causing progressive dysphagia and malnutrition, that required admission to our Department. At the admission neurological examination revealed a continuous segmental axial and brachial dystonias and complex stereotypies (pelvis rocking) (Fig.1A)