ABSTRACT
OBJECTIVE: To study the clinical picture of all patients with GNAO1 encephalopathy detected in the Russian Federation. This publication is a multicenter study combining data from epileptological centers in Moscow, Novosibirsk, St. Petersburg, Nizhny Novgorod, Tyumen. MATERIAL AND METHODS: Nine patients were included, aged 2 to 19 years, with 4 mutations. Male to female sex ratio = 5:4. RESULTS: 8 patients (5 with mutation c.607G>A (p.Gly203Arg), 1 - c.155A>G (Gln52Arg), 1 - c.485G>A (p.Arg162Gln)) had a variant of epileptic encephalopathy, developmental encephalopathy, 1 patient had torsion dystonia without epilepsy (mutation c.713A>G (p.Asp238Gly)). Epileptic seizures in 8 children with epileptic encephalopathy GNAO1 in 100% debuted at 1 month of life, becoming the earliest symptom of the disease. Motor development delayed in 100% of cases. Mental development was not affected only in the case of the dystonic variant. Hyperkinesis (dystonia, choreoathetosis, ballism) followed later, from 2 to 8 months. They were more severe than epilepsy. 4 patients with the c.607G>A (p.Gly203Arg) mutation developed repeated dystonic storms that were resistant to most drugs. CONCLUSION: Epilepsy in GNAO1 is difficult to treat, but temporary or complete remission is possible. Effective drug strategies for the treatment of hyperkinesis have not yet been developed. Expansion of indications for surgical therapy (DBS) of hyperkinesis in this syndrome is desirable.
Subject(s)
Brain Diseases , Dyskinesias , Epilepsy, Generalized , Epilepsy , Child , Female , Humans , Male , Epilepsy/genetics , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , Hyperkinesis , Mutation , Seizures , Child, Preschool , Adolescent , Young AdultABSTRACT
OBJECTIVE: To study the literature data and a series of our cases regarding the epilepsy clinic, electroencephalographic changes and other phenotypic features in X-linked intellectual disability (ID) caused by KIAA2022 mutations. MATERIAL AND METHODS: We analyzed the anamnesis of the disease, using medical records from different Russian medical organizations, as well as the results of the genealogical anamnesis, clinical, genetic, electroencephalographic (EEG) and neuroimaging (brain MRI ) examinations of 7 patients (5 girls and 2 boys aged 5 to 13 years) with a confirmed diagnosis of X-linked ID caused by KIAA2022 mutations, in whom the clinical picture of the underlying disease was combined with epilepsy. RESULTS: The main common phenotypic features of patients with X-linked ID caused by the KIAA2022 mutations are mental retardation, lack of phrasal speech, motor developmental delay, and dysmorphism. The prominent epilepsy characteristics are myoclonic, atonic seizures with nods, flinches, body propulsions, atypical absences, and diffuse discharges «spike-polyspike-slow wave¼ on the EEG. No pathognomonic brain changes were found on MRI. In many cases, the absence of the effect of antiepileptic therapy was noted. CONCLUSION: The described cases of X-linked ID in combination with epilepsy show that this disease can be seen in males as well as in females, epilepsy is rather characterized by generalized seizures, and it is pharmacoresistant in many cases. There is a need for further research on this rare genetic syndrome.