AP-HP, Service de Neuropédiatrie, Hôpital Trousseau, Paris, France.
J Neurol Neurosurg Psychiatry. 2012 Oct;83(10):956-62. doi: 10.1136/jnnp-2012-302505. Epub 2012 Jul 24.
Benign hereditary chorea (BHC) is a rare autosomal dominant disorder characterised by childhood onset that tends to improve in adulthood. The associated gene, NKX2-1 (previously called TITF1), is essential for organogenesis of the basal ganglia, thyroid and lungs. The aim of the study was to refine the movement disorders phenotype. We also studied disease course and response to therapy in a large series of genetically proven patients.
We analysed clinical, genetic findings and follow-up data in 28 NKX2-1 mutated BHC patients from 13 families.
All patients had private mutations, including seven new mutations, three previously reported mutations and three sporadic deletions encompassing the NKX2-1 gene. Hypotonia and chorea were present in early infancy, with delayed walking ability (25/28); dystonia, myoclonus and tics were often associated. Attention deficit hyperactivity disorder (ADHD) was present in seven. Among the 14 patients followed-up until adulthood, nine had persistent mild chorea, two had near total resolution of chorea but persistent disabling prominent myoclonus and three recovered completely. Learning difficulties were observed in 20/28 patients, and three had mental retardation. Various combinations of BHC, thyroid (67%) and lung (46%) features were noted. We found no genotype-phenotype correlation. A rapid and sustained beneficial effect on chorea was obtained in 5/8 patients treated with tetrabenazine.
Early onset chorea preceded by hypotonia is suggestive of BHC. Associated thyroid or respiratory disorders further support the diagnosis and call for genetic studies. Tetrabenazine may be an interesting option to treat disabling chorea.
良性遗传性舞蹈病（BHC）是一种罕见的常染色体显性遗传病，其特征为儿童期起病，成年后趋于改善。相关基因 NKX2-1（以前称为 TITF1）对于基底节、甲状腺和肺的器官发生至关重要。本研究旨在细化运动障碍表型。我们还研究了大量经基因证实的患者的疾病过程和对治疗的反应。
我们分析了 13 个家族的 28 名 NKX2-1 突变 BHC 患者的临床、遗传发现和随访数据。
所有患者均有私人突变，包括 7 种新突变、3 种以前报道的突变和 3 种包含 NKX2-1 基因的散发性缺失。所有患者均在婴儿早期出现张力减退和舞蹈症，行走能力延迟（28 例中有 25 例）；常伴有肌张力障碍、肌阵挛和抽搐。7 例存在注意缺陷多动障碍（ADHD）。14 名随访至成年的患者中，9 例持续性轻度舞蹈症，2 例舞蹈症基本完全缓解但持续性致残性显著肌阵挛，3 例完全缓解。28 例患者中有 20 例存在学习困难，3 例智力迟钝。注意到 BHC、甲状腺（67%）和肺部（46%）特征的各种组合。我们没有发现基因型-表型相关性。5 例接受四苯嗪治疗的患者中，有 4 例观察到舞蹈症迅速和持续改善。
以张力减退为前驱的早期起病的舞蹈症提示为 BHC。伴发的甲状腺或呼吸系统疾病进一步支持诊断，并呼吁进行基因研究。四苯嗪可能是治疗致残性舞蹈症的一个有趣选择。
