PDF(Pubmed)
Abstract：
UNASSIGNED: Rho-related BTB domain-containing protein 2 (RHOBTB2) is a protein that interacts with cullin-3, a crucial E3 ubiquitin ligase for mitotic cell division. RHOBTB2 has been linked to early infantile epileptic encephalopathy, autosomal dominant type 64 (OMIM618004), in 34 reported patients.
UNASSIGNED: We present a case series of seven patients with RHOBTB2-related disorders (RHOBTB2-RD), including a description of a novel heterozygous variant. We also reviewed previously published cases of RHOBTB2-RD.
UNASSIGNED: The seven patients had ages ranging from 2 years and 8 months to 26 years, and all had experienced seizures before the age of one (onset, 4-12 months, median, 4 months), including various types of seizures. All patients in this cohort also had a movement disorder (onset, 0.3-14 years, median, 1.5 years). Six of seven had a baseline movement disorder, and one of seven only had paroxysmal dystonia. Stereotypies were noted in four of six, choreodystonia in three of six, and ataxia in one case with multiple movement phenotypes at baseline. Paroxysmal movement disorders were observed in six of seven patients for whom carbamazepine or oxcarbazepine treatment was effective in controlling acute or paroxysmal movement disorders. Four patients had acute encephalopathic episodes at ages 4 (one patient) and 6 (three patients), which improved following treatment with methylprednisolone. Magnetic resonance imaging scans revealed transient fluid-attenuated inversion recovery abnormalities during these episodes, as well as myelination delay, thin corpus callosum, and brain atrophy. One patient had a novel RHOBTB2 variant (c.359G>A/p.Gly120Glu).
UNASSIGNED: RHOBTB2-RD is characterized by developmental delay or intellectual disability, early-onset seizures, baseline movement disorders, acute or paroxysmal motor phenomena, acquired microcephaly, and episodes of acute encephalopathy. Early onsets of focal dystonia, acute encephalopathic episodes, episodes of tongue protrusion, or peripheral vasomotor disturbances are important diagnostic clues. Treatment with carbamazepine or oxcarbazepine was found to be effective in controlling acute or paroxysmal movement disorders. Our study highlights the clinical features and treatment response of RHOBTB2-RD.
UNASSIGNED: We present a case series of seven patients with RHOBTB2-related disorders (RHOBTB2-RD), including a description of a novel heterozygous variant. We also reviewed previously published cases of RHOBTB2-RD.
UNASSIGNED: The seven patients had ages ranging from 2 years and 8 months to 26 years, and all had experienced seizures before the age of one (onset, 4-12 months, median, 4 months), including various types of seizures. All patients in this cohort also had a movement disorder (onset, 0.3-14 years, median, 1.5 years). Six of seven had a baseline movement disorder, and one of seven only had paroxysmal dystonia. Stereotypies were noted in four of six, choreodystonia in three of six, and ataxia in one case with multiple movement phenotypes at baseline. Paroxysmal movement disorders were observed in six of seven patients for whom carbamazepine or oxcarbazepine treatment was effective in controlling acute or paroxysmal movement disorders. Four patients had acute encephalopathic episodes at ages 4 (one patient) and 6 (three patients), which improved following treatment with methylprednisolone. Magnetic resonance imaging scans revealed transient fluid-attenuated inversion recovery abnormalities during these episodes, as well as myelination delay, thin corpus callosum, and brain atrophy. One patient had a novel RHOBTB2 variant (c.359G>A/p.Gly120Glu).
UNASSIGNED: RHOBTB2-RD is characterized by developmental delay or intellectual disability, early-onset seizures, baseline movement disorders, acute or paroxysmal motor phenomena, acquired microcephaly, and episodes of acute encephalopathy. Early onsets of focal dystonia, acute encephalopathic episodes, episodes of tongue protrusion, or peripheral vasomotor disturbances are important diagnostic clues. Treatment with carbamazepine or oxcarbazepine was found to be effective in controlling acute or paroxysmal movement disorders. Our study highlights the clinical features and treatment response of RHOBTB2-RD.
摘要：
■含有Rho相关BTB结构域的蛋白2（RHOBTB2）是一种与cullin-3相互作用的蛋白，cullin-3是有丝分裂细胞分裂的关键E3泛素连接酶。RHOBTB2与早期婴儿癫痫性脑病有关，常染色体显性64型（OMIM618004），在34例报告患者中。
■我们介绍了7例RHOBTB2相关疾病（RHOBTB2-RD）患者的病例系列，包括新的杂合变体的描述。我们还回顾了以前发表的RHOBTB2-RD病例。
■7名患者的年龄从2岁8个月到26岁不等,并且所有人在一岁之前都经历过癫痫发作（发作，4-12个月,中位数，4个月),包括各种类型的癫痫发作。该队列中的所有患者还患有运动障碍（发作，0.3-14年，中位数，1.5年）。七个人中有六个有基线运动障碍，七个人中只有一个有阵发性肌张力障碍.六个人中有四个出现了刻板印象，六分之三的舞蹈性张力障碍，和共济失调在基线有多个运动表型的一个案例。在7例患者中，有6例观察到阵发性运动障碍，卡马西平或奥卡西平治疗可有效控制急性或阵发性运动障碍。四名患者在4岁（一名患者）和6岁（三名患者）出现急性脑病发作，甲基强的松龙治疗后有所改善。磁共振成像扫描显示，在这些发作期间，短暂的液体衰减的反转恢复异常，以及髓鞘形成延迟，薄的call体，和脑萎缩.一名患者有一个新的RHOBTB2变体（c.359G>A/p。Gly120Glu）。
■RHOBTB2-RD的特征是发育迟缓或智力障碍，早发性癫痫发作,基线运动障碍，急性或阵发性运动现象，获得性小头畸形,和急性脑病的发作。局灶性肌张力障碍的早期发作，急性脑病发作，舌头突出的发作，或周围血管舒缩障碍是重要的诊断线索。发现卡马西平或奥卡西平治疗可有效控制急性或阵发性运动障碍。我们的研究强调了RHOBTB2-RD的临床特征和治疗反应。
■我们介绍了7例RHOBTB2相关疾病（RHOBTB2-RD）患者的病例系列，包括新的杂合变体的描述。我们还回顾了以前发表的RHOBTB2-RD病例。
■7名患者的年龄从2岁8个月到26岁不等,并且所有人在一岁之前都经历过癫痫发作（发作，4-12个月,中位数，4个月),包括各种类型的癫痫发作。该队列中的所有患者还患有运动障碍（发作，0.3-14年，中位数，1.5年）。七个人中有六个有基线运动障碍，七个人中只有一个有阵发性肌张力障碍.六个人中有四个出现了刻板印象，六分之三的舞蹈性张力障碍，和共济失调在基线有多个运动表型的一个案例。在7例患者中，有6例观察到阵发性运动障碍，卡马西平或奥卡西平治疗可有效控制急性或阵发性运动障碍。四名患者在4岁（一名患者）和6岁（三名患者）出现急性脑病发作，甲基强的松龙治疗后有所改善。磁共振成像扫描显示，在这些发作期间，短暂的液体衰减的反转恢复异常，以及髓鞘形成延迟，薄的call体，和脑萎缩.一名患者有一个新的RHOBTB2变体（c.359G>A/p。Gly120Glu）。
■RHOBTB2-RD的特征是发育迟缓或智力障碍，早发性癫痫发作,基线运动障碍，急性或阵发性运动现象，获得性小头畸形,和急性脑病的发作。局灶性肌张力障碍的早期发作，急性脑病发作，舌头突出的发作，或周围血管舒缩障碍是重要的诊断线索。发现卡马西平或奥卡西平治疗可有效控制急性或阵发性运动障碍。我们的研究强调了RHOBTB2-RD的临床特征和治疗反应。
