RHOBTB2 gene associated epilepsy and paroxysmal movement disorder: two cases report and literature review

Quanzhen Tan,Ying Yang,Jie Zhang,Yan Sun,Miaomiao Cheng,Xueyang Niu,Yuehua Zhang

doi:10.1186/s42494-021-00056-y

Abstract

BackgroundRHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64), which is characterized by epilepsy, developmental delay, microcephaly, unspecific facial dysmorphism, and paroxysmal movement disorders. Most previous studies showed that the phenotypes of RHOBTB2 gene include developmental and epileptic encephalopathy(DEE) and DEE with paroxysmal movement disorders. Only one study showed that patient with RHOBTB2 variant had paroxysmal movement disorders with no epilepsy.Case presentationsTwo cases with RHOBTB2 variants are presented here: Case one was diagnosed as DEE, he had recurrent afebrile focal status epilepticus and paroxysmal extrapyramidal symptoms in infancy. Interictal electroencephalogram (EEG) showed focal discharges. Brain magnetic resonance imaging (MRI) showed cortical dysplasia. Epilepsy of case one was refractory. Nevertheless, case two only showed paroxysmal movement disorders alone in adolescence. Video EEG showed focal discharges during an interictal dystonic episode and he brain MRI was normal.ConclusionThe phenotypes of RHOBTB2 gene include DEE, paroxysmal movement disorders, and DEE with paroxysmal movement disorders. RHOBTB2 can be one of the pathogenic genes of paroxysmal movement disorders.

Highlights

RHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64), which is characterized by epilepsy, developmental delay, microcephaly, unspecific facial dysmorphism, and paroxysmal movement disorders
RHOBTB2 is composed of a GTPase domain, a proline-rich region, a tandem of two BTB domains, and a conserved C-terminal region, and it is highly expressed in neuronal tissues [1]
Eighteen patients with RHOBTB2 variants had characterized of Developmental and epileptic encephalopathy (DEE), among them, 13 patients showed paroxysmal movement disorders, including dystonia, dyskinesia, athetosis and choreatic features

Summary

Background

Rho-related BTB domain-containing protein 2(RHOBTB2; MIM: 607,352) is an atypical Rho GTPase, which is mapped to chromosome 8p21.2 and contains 9 exons. Straub et al [3] identified 5 RHOBTB2 variants in 10 patients with developmental and epileptic encephalopathy-64 (DEE64; MIM: 618,004), all of the variants affected BTB domains They showed varied clinical manifestations, including epilepsy, developmental delay, hemiparesis, paroxysmal movement disorders and microcephaly. Most studies showed that patients with RHOBTB2 variants had DEE and some of them had paroxysmal movement disorders. One patient reported previously had paroxysmal movement disorders without a typical epileptic seizure This patient had complex hyperkinetic movements at 6 months of age, followed by generalized choreodystonia and dystonia at 3 years old. She had developmental milestones delay, microcephaly and facial. One patient with paroxysmal movement disorders had responded to carbamazepine

Discussion

Conclusion