Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder

详细信息    查看全文

• 作者：Amitha L. Ananth ; MD^a ; ¹ ; ^{Amitha@stanford.edu" class="auth_mail" title="E-mail the corresponding author} ; Amy Robichaux-Viehoever ; MD ; PhD^b ; ^c ; ¹ ; ^{amy.viehoever@UCSF.edu" class="auth_mail" title="E-mail the corresponding author} ; Young-Min Kim ; ​MD^d ; Andrea Hanson-Kahn ; MS ; CGC^a ; ^e ; Rachel Cox ; MS ; CGC^a ; Gregory M. Enns ; MB ; ChB^a ; Jonathan Strober ; MD^b ; ^c ; Marcia Willing ; MD^f ; Bradley L. Schlaggar ; MD ; PhD^d ; ^f ; ^g ; ^h ; ⁱ ; Yvonne W. Wu ; MD ; MPH^b ; ^c ; ² ; Jonathan A. Bernstein ; MD ; PhD^a ; ²
• 关键词：GNAO1 ; chorea ; ballismus ; whole exome sequencing ; movement disorder
• 刊名：Pediatric Neurology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：59
• 期：Complete
• 页码：81-84
• 全文大小：184 K

文摘

Mutations in GNAO1 have been described in 11 patients to date. Although most of these individuals had epileptic encephalopathy, four patients had a severe movement disorder as the prominent feature. We describe the largest series of patients with de novoGNAO1 mutations who have severe chorea, developmental delay, and hypotonia in the absence of epilepsy.

Methods

Six patients with recurrent missense mutations in GNAO1 as detected by whole exome sequencing were identified at three institutions. We describe the presentation, clinical course, and response to treatment of these patients.

Results

All six patients exhibited global developmental delay and hypotonia from infancy. Chorea developed by age four years in all but one patient, who developed chorea at 14 years. Treatments with neuroleptics and tetrabenazine were most effective in the baseline management of chorea. The chorea became gradually progressive and marked by episodes of severe, refractory ballismus requiring intensive care unit admissions in four of six patients. Exacerbations indirectly led to the death of two patients.

Conclusions

Patients with GNAO1 mutations can present with a severe, progressive movement disorder in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life-threatening secondary complications. Early and aggressive treatment of these exacerbations with direct admission to intensive care units for treatment with anesthetic drips may prevent some secondary complications. However the chorea and ballismus can be refractory to maximum medical therapy.