Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Department of Medical Genetics, University of Antwerp, Prins Boudewijnlaan 43, 2650, Edegem, Belgium.
Calcif Tissue Int. 2019 May;104(5):554-560. doi: 10.1007/s00223-019-00532-1. Epub 2019 Feb 5.
Camurati-Engelmann disease or progressive diaphyseal dysplasia is a rare autosomal dominant sclerosing bone dysplasia. Mainly the skull and the diaphyses of the long tubular bones are affected. Clinically, the patients suffer from bone pain, easy fatigability, and decreased muscle mass and weakness in the proximal parts of the lower limbs resulting in gait disturbances. The disease-causing mutations are located within the TGFβ-1 gene and expected to or thought to disrupt the binding between TGFβ1 and its latency-associated peptide resulting in an increased signaling of the pathway and subsequently accelerated bone turnover. In preclinical studies, it was shown that targeting the type I receptor ameliorates the high bone turnover. In patients, treatment options are currently mostly limited to corticosteroids that may relieve the pain, and improve the muscle weakness and fatigue. In this review, the clinical and radiological characteristics as well as the molecular genetics of this condition are discussed.
卡穆拉特-恩格尔曼病或进行性骨干发育不良是一种罕见的常染色体显性硬化性骨发育不良。主要受影响的是颅骨和长管状骨的骨干。临床上,患者会出现骨痛、易疲劳、四肢近端肌肉量减少和无力,导致步态障碍。致病突变位于 TGFβ-1 基因内,预计或认为会破坏 TGFβ1 与其潜伏相关肽之间的结合,从而导致该途径的信号转导增加,并随后加速骨转换。在临床前研究中,已经表明靶向 I 型受体可以改善高骨转换。在患者中,目前的治疗选择主要限于皮质类固醇,皮质类固醇可能缓解疼痛,并改善肌肉无力和疲劳。在这篇综述中,讨论了这种疾病的临床和放射学特征以及分子遗传学。