García-Cabezas M A, García-Alix A, Martín Y, Gutiérrez M, Hernández C, Rodríguez J I, Morales C
Departamento de Anatomía Patológica, Hospital Universitario La Paz, Pso. de la Castellana 261, 28046 Madrid, Spain.
Acta Neuropathol. 2004 May;107(5):475-8. doi: 10.1007/s00401-004-0825-3. Epub 2004 Feb 13.
We present the case of a floppy neonate with marked and generalized weakness, respiratory insufficiency and fetal akinesia deformation sequence. The infant showed multiple joint contractures, two bone fractures and needed mechanical ventilation from birth to death at 16 days of age. Electrophysiological assessment showed electrically unexcitable motor and sensory nerves. Muscle biopsy showed diffuse atrophy of type I and type II fibers. Necropsy confirmed the diagnosis of infantile spinal muscular atrophy (SMA) with severe loss of motor neurons in anterior horns and motor nuclei of brainstem. There were also neuronal loss, gliosis, chromatolysis, ballooned cells, empty cell beds and neuronophagia figures in other brainstem and brain nuclei. Genetic analysis of the patient revealed homozygous deletions of survival motor neuron gene 1 (SMN1) and a single copy of SMN2 in region 5q13. This case confirms that the loss of spinal motor neurons underlies the muscular atrophy in severe cases of 5q SMA. This case also shows that the presence of multiple joint contractures, bone fractures and respiratory insufficiency in SMA in the neonatal period does not necessarily exclude the occurrence of classical deletions in the SMA 5q13 region. Rather, these atypical clinical findings show the extreme severity and prenatal onset of the disease in these SMA cases, which may be related with the occurrence of a single copy of SMN2 gene. More reports of clinically, pathologically and genetically well-documented cases are essential to define the different types of this disease.
我们报告了一例松软的新生儿病例，该患儿有明显的全身无力、呼吸功能不全及胎儿运动减少变形序列征。婴儿表现出多处关节挛缩、两处骨折，从出生到16日龄死亡期间均需要机械通气。电生理评估显示运动和感觉神经对电刺激无反应。肌肉活检显示I型和II型纤维弥漫性萎缩。尸检证实为婴儿脊髓性肌萎缩症（SMA），前角和脑干运动核的运动神经元严重丧失。在其他脑干和脑核中也存在神经元丢失、胶质细胞增生、染色质溶解、气球样细胞、空细胞床和噬神经细胞现象。对该患者的基因分析显示，生存运动神经元基因1（SMN1）纯合缺失，5q13区域有一个单拷贝的SMN2。该病例证实，脊髓运动神经元的丧失是5q型SMA严重病例中肌肉萎缩的基础。该病例还表明，新生儿期SMA出现多处关节挛缩、骨折和呼吸功能不全并不一定排除5q13区域经典缺失的发生。相反，这些非典型临床表现表明这些SMA病例病情极其严重且产前发病，这可能与单拷贝SMN2基因的出现有关。更多临床、病理和基因记录完整的病例报告对于明确该疾病的不同类型至关重要。
