Salih M A, Al Rayess M, Cutshall S, Urtizberea J A, Al-Turaiki M H, Ozo C O, Straub V, Akbar M, Abid M, Andeejani A, Campbell K P
Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Neuropediatrics. 1998 Dec;29(6):289-93. doi: 10.1055/s-2007-973579.
We report on two brothers (the product of first-degree consanguineous marriage; aged 15 and 12 years) who presented with severe hypotonia at birth, proximal muscle weakness associated with delayed motor milestones but normal cognitive function. Investigations (at 4 years of age) revealed mildly elevated serum creatine kinase (CK) levels (300 and 824 IU/l; N < or = 210). Muscle biopsies showed minimal change myopathy, no neurogenic atrophy but remarkable type-1 fibre predominance (up to 85.5%) without fibre-type disproportion. Clinical examination at 12 and 9 years, respectively, showed mild facial weakness and high-arched palate in both patients. The younger sibling also had ptosis but otherwise normal external ocular muscles. They showed symmetric proximal muscle weakness and wasting associated with calf-muscle hypertrophy. They could walk independently. A repeat muscle biopsy showed advanced dystrophic changes in the younger patient at the age of 10 years. Virtually all the remaining fibres were type 1. Immunohistochemistry revealed normal expression of the dystrophin-glycoprotein complex (DGC), including dystrophin, beta-dystroglycan, alpha-(adhalin), beta-, gamma-, and delta-sarcoglycan, laminin-alpha2 chain (merosin) and syntrophin. Mild dystrophic features and type-1 fibre predominance (92.5%) were seen in the biopsy of the older patient, whereas immunohistochemistry showed normal expression of the DGC. Both cases also showed clear expression of integrin alpha7 at the muscle fibre surface and in the blood vessels. Three years later, they could still walk, but with difficulty, and the older brother showed enlargement of the tongue and echocardiographic features of left ventricular dilated cardiomyopathy.
我们报告了一对兄弟（一级近亲结婚所生；年龄分别为15岁和12岁），他们出生时即表现出严重的肌张力减退，近端肌肉无力，伴有运动发育迟缓，但认知功能正常。检查（4岁时）发现血清肌酸激酶（CK）水平轻度升高（分别为300和824 IU/l；正常范围N≤210）。肌肉活检显示为轻度改变性肌病，无神经源性萎缩，但1型纤维显著占优势（高达85.5%），无纤维类型比例失调。分别在12岁和9岁时进行的临床检查显示，两名患者均有轻度面部无力和高拱腭。弟弟还有上睑下垂，但外眼肌其他方面正常。他们表现出对称性近端肌肉无力和萎缩，并伴有小腿肌肉肥大。他们能够独立行走。10岁时对弟弟进行的重复肌肉活检显示有晚期营养不良性改变。几乎所有剩余纤维均为1型。免疫组织化学显示肌营养不良蛋白-糖蛋白复合物（DGC）表达正常，包括肌营养不良蛋白、β-肌营养不良聚糖、α-（衔接蛋白）、β-、γ-和δ-肌聚糖、层粘连蛋白-α2链（merosin）和肌营养不良蛋白相关蛋白。在哥哥的活检中可见轻度营养不良特征和1型纤维占优势（92.5%），而免疫组织化学显示DGC表达正常。两例患者在肌纤维表面和血管中均清晰表达整合素α7。三年后，他们仍能行走，但困难重重哥哥出现舌头肿大，超声心动图显示左心室扩张型心肌病的特征。
