早发性骨关节炎、夏科-马里-图思病样神经病变、自身免疫特征、多发性动脉动脉瘤和夹层：一种未被认识且危及生命的病症。
Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.
作者信息
Aubart Mélodie, Gobert Delphine, Aubart-Cohen Fleur, Detaint Delphine, Hanna Nadine, d'Indya Hyacintha, Lequintrec Janine-Sophie, Renard Philippe, Vigneron Anne-Marie, Dieudé Philippe, Laissy Jean-Pierre, Koch Pierre, Muti Christine, Roume Joelle, Cusin Veronica, Grandchamp Bernard, Gouya Laurent, LeGuern Eric, Papo Thomas, Boileau Catherine, Jondeau Guillaume
机构信息
INSERM U698, Hôpital Bichat, Paris, France.
AP-HP, Hôpital Bichat, Service de Médecine Interne, Hôpital Bichat, Paris, France.
出版信息
PLoS One. 2014 May 7;9(5):e96387. doi: 10.1371/journal.pone.0096387. eCollection 2014.
BACKGROUND
Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined.
METHODS
All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases.
RESULTS
Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients.
INTERPRETATION
SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.
背景
严重骨关节炎和胸主动脉瘤最近被发现与SMAD3基因突变有关，但完整的临床谱尚未完全明确。
方法
对所有前来我们中心的SMAD3基因突变携带者及其家属进行前瞻性研究，采用结构化方案，包括标准化临床检查、血液检查、全身计算机断层扫描、关节X线检查。对部分病例进行了神经电生理检查。
结果
在我们中心共识别出34名SMAD3基因突变携带者，另有16名亲属因主动脉手术或猝死被认为患病（共50名受试者）。72%的患者存在主动脉疾病，其中56%在平均年龄45岁时并发主动脉夹层、接受手术或猝死。78%的患者存在颈动脉瘤或迂曲，44%的患者其他动脉受累，包括冠状动脉夹层。总体而言，95%的突变携带者表现出主动脉或主动脉外动脉疾病。大多数患者还存在手足发绀。所有患者均有骨关节炎表现。关节受累可能很严重，年轻患者需要手术治疗，受累关节部位不寻常，如跗骨或肩部，或表现为类似晶体性关节炎伴纤维软骨钙化。68%的患者有神经症状，9例患有周围神经病变。神经电生理检查在3个不同家族中发现轴索性运动和感觉神经病变，很像II型遗传性运动感觉神经病（CMT2），尽管这些家族中已知的CMT2基因均无突变。36%的患者有自身免疫特征，包括干燥综合征、类风湿关节炎、桥本甲状腺炎或孤立性自身抗体。
解读
SMAD3基因突变与主动脉扩张、骨关节炎有关，还与自身免疫和类似II型遗传性运动感觉神经病的周围神经病变有关。
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