Rudnik-Schöneborn S, Forkert R, Hahnen E, Wirth B, Zerres K
Institute for Human Genetics, University of Bonn, Germany.
Neuropediatrics. 1996 Feb;27(1):8-15. doi: 10.1055/s-2007-973741.
With the evidence of deletions in the region responsible for autosomal recessive spinal muscular atrophy (SMA) on chromosome 5, it is now possible to further clarify the clinical and diagnostic findings in proximal SMA. Homozygous deletions of the survival motor neuron (SMN) gene can be detected in about 95% of patients with early onset SMA. In a series of more than 200 patients, we tested 31 patients with atypical features of SMA who fulfilled at least one exclusion criterion according to the diagnostic criteria of the International SMA Consortium for the presence of SMN gene deletions. The patients were subdivided into two groups: 1. Seven index patients being not deleted for the SMN gene who belonged to a well-defined SMA plus variant that has already been shown to be unlinked with chromosome 5q markers: diaphragmatic SMA, SMA plus olivopontocerebellar hypoplasia, SMA with congenital arthrogryposis and bone fractures. 2. Twenty-four patients with clinical signs of SMA and neurogenic findings in EMG/muscle biopsy who had unusual features or other organ involvement. In order to structure this heterogeneous group, each patient was assigned to a subgroup according to the leading atypical feature. In 5 out of 8 unrelated patients with a history of preterm birth and/or perinatal asphyxia leading to a picture of severe SMA in combination with respiratory distress and/or cerebral palsy, no deletion of the SMN gene could be detected. There were five unrelated patients with extended central nervous system involvement (cerebral atrophy, EEG abnormalities, pyramidal tract signs, evidence of cerebellar involvement). Most of these patients (4/5) proved to belong to SMA 5q on the basis of SMN gene deletion findings. The same applied to a group of three patients with classical SMA in association with congenital malformations (mainly heart defect). A fourth group of three patients was characterized mainly by an unusual improvement of the condition; in these patients no SMN gene deletions were present. In three index patients a more complex syndrome of the CNS and other organs was suggested, but the detection of SMN gene deletions in two of them made a coincidence of features more likely. In addition, SMN gene deletions were found in two patients with evidence of congenital fibre type dysproportion in one and extremely raised CK activity ( > 10fold) in the other. While the confirmation of SMN gene deletions is very useful in cases with diagnostic doubts, caution is required when offering prenatal prediction with regard to SMA 5q in families with atypical features. There is strong evidence that there are clinical entities resembling SMA which most likely have another pathogenetic background.
鉴于5号染色体上与常染色体隐性脊髓性肌萎缩症（SMA）相关区域存在缺失的证据，现在有可能进一步明确近端SMA的临床和诊断特征。约95%早发型SMA患者可检测到存活运动神经元（SMN）基因的纯合缺失。在一系列200多名患者中，我们对31例具有SMA非典型特征的患者进行了检测，这些患者根据国际SMA协会的诊断标准至少符合一项排除标准，以检测是否存在SMN基因缺失。患者被分为两组：1. 7例索引患者未检测到SMN基因缺失，他们属于一种已被证明与5号染色体q臂标记无关的明确的SMA加综合征变体：膈神经麻痹型SMA、SMA加橄榄脑桥小脑发育不全、伴有先天性关节挛缩和骨折的SMA。2. 24例具有SMA临床体征且肌电图/肌肉活检有神经源性表现的患者，他们具有不寻常特征或其他器官受累情况。为了对这个异质性群体进行分类，根据主要非典型特征将每位患者分配到一个亚组。在8例有早产和/或围产期窒息史、导致严重SMA合并呼吸窘迫和/或脑瘫表现的非相关患者中，有5例未检测到SMN基因缺失。有5例非相关患者有广泛的中枢神经系统受累（脑萎缩、脑电图异常、锥体束征、小脑受累证据）。根据SMN基因缺失结果，这些患者中的大多数（4/5）被证明属于5q型SMA。这同样适用于一组3例伴有先天性畸形（主要是心脏缺陷）的典型SMA患者。第四组3例患者的主要特征是病情有不寻常改善；这些患者不存在SMN基因缺失。在3例索引患者中，提示存在更复杂的中枢神经系统和其他器官综合征，但其中2例检测到SMN基因缺失，使得特征巧合的可能性更大。此外，在1例有先天性纤维类型比例失调证据的患者和另1例肌酸激酶活性极度升高（>10倍）的患者中发现了SMN基因缺失。虽然在诊断存疑的病例中确认SMN基因缺失非常有用，但在为具有非典型特征的家庭提供5q型SMA的产前预测时需要谨慎。有强有力的证据表明，存在一些类似于SMA的临床实体，其发病机制很可能不同。
