Division of Medical Genetics, Department of Pediatrics, Stanford University, Lucile Packard Children's Hospital, Stanford, California 94305-5208, USA.
Am J Med Genet A. 2012 Sep;158A(9):2353-7. doi: 10.1002/ajmg.a.35533. Epub 2012 Aug 7.
Amyoplasia congenita is a distinct form of arthrogryposis with characteristic features including internally rotated and adducted shoulders, extended elbows, flexion, and ulnar deviation of the wrists, and adducted thumbs. Fetal hypokinesia, secondary to a variety of genetic conditions, neuromuscular disorders, and environmental agents, is associated with contractures. In order to increase our understanding of the phenotypic spectrum associated with SURF 1 deficiency, a common cause of mitochondrial respiratory chain complex IV deficiency and Leigh syndrome, we describe a now 6-year-old boy who presented in the neonatal period with amyoplasia congenita. His development was normal until age 10.5 months, at which time he developed severe hypotonia and choreoathetosis following an episode of viral gastroenteritis. Following the onset of neurological symptoms, he gradually developed severe kyphosis and lower limb contractures. Blood and cerebrospinal fluid lactate levels were elevated and head imaging showed characteristic features of Leigh syndrome. He was found to harbor two pathogenic heterozygous mutations in the SURF 1 gene. In this case, mitochondrial dysfunction and the resultant energy deficiency may have played a role in causing abnormal neuronal development during embryogenesis, causing arthrogryposis. A variety of mitochondrial respiratory chain complex deficiencies have been associated with contractures of varying severity. Therefore, mitochondrial disorders should be considered in the differential diagnosis of neonatal arthrogryposis, especially if other characteristic findings such as lactic acidemia or basal ganglia abnormalities are present.
先天性关节挛缩症是一种独特的关节挛缩症形式，具有特征性表现，包括内旋和内收的肩部、伸展的肘部、弯曲和尺侧偏斜的手腕以及内收的拇指。胎儿运动减少是由多种遗传条件、神经肌肉疾病和环境因素引起的，与挛缩有关。为了增加我们对 SURF1 缺乏相关表型谱的理解，SURF1 缺乏是线粒体呼吸链复合物 IV 缺乏和 Leigh 综合征的常见原因，我们描述了一个现在 6 岁的男孩，他在新生儿期表现为先天性关节挛缩症。他的发育正常，直到 10.5 个月大，当时他在病毒性肠胃炎发作后出现严重的低张力和舞蹈手足徐动症。在神经系统症状出现后，他逐渐出现严重的脊柱后凸和下肢挛缩。血液和脑脊液中的乳酸水平升高，头部成像显示 Leigh 综合征的特征性表现。他被发现携带 SURF1 基因中的两个致病性杂合突变。在这种情况下，线粒体功能障碍和由此产生的能量缺乏可能在胚胎发生过程中导致神经元发育异常，从而导致关节挛缩症。多种线粒体呼吸链复合物缺乏症与不同严重程度的挛缩有关。因此，在新生儿关节挛缩症的鉴别诊断中应考虑线粒体疾病，特别是如果存在其他特征性发现，如乳酸血症或基底节异常。
