Camurati–Engelmann Disease

Abstract

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 are thought to disrupt the binding between TGFβ1 and its latency associated peptide resulting in an increased signalling 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, 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.

Clinical Characteristics And Identification of Novel TGF-β1 Mutation In Three Unrelated Chinese Families With Progressive Diaphyseal Dysplasia

“…R218C, R218H and C225R of TGF-β1 gene are the most frequently occurred mutations in patients with PDD, among them R218C substitution is the hotspot, accounting for approximately 60% of all the mutations [4]. Previous studies also reported three different mutations of Cys at position 223: C223R, C223S and C223G additionally [3]. In our study, a novel mutation C223W was detected, which broadened the mutation spectrum of pathogenic genes in Chinese.…”

“…Waddling gait, pain in extremities, muscular weakness, and cortical thickening of the diaphysis of the long bones [1,2] are the hallmark clinical manifestations and imaging features. If the lesions involve skull, will lead to cranial nerve damage, such as hearing impairment and vision loss [3,4]. Some cases have systemic manifestations or like some kind of syndromes, accompanied with anemia, leukopenia and hepatosplenomegaly for instance [5].…”

Progressive diaphyseal dysplasia: a rare bone disorder with alarming radiographs

“…1,2 Progressive diaphyseal dysplasia, also known as Camurati-Engelmann disease, is a disease belonging to this entity. [3][4][5] It is an autosomal dominant disorder due to mutation in transforming growth factor-β1. This in turn leads to a disorder of intramembranous ossification, and results in hyperostosis.…”

“…The age at which the diagnosis of progressive diaphyseal dysplasia is reached, the clinical manifestations of disease and the extent of radiological evidence of sclerosis are variable. 4,5 Disease progression is slow and unpredictable. Treatment of the disease aims for symptomatic relief, with losartan reported to be effective in relieving limb pain based on the mechanism of down-regulation of transforming growth factor-β1 receptor expression.…”

Focal and Osteosclerotic Bone Diseases

“…The review of Camurati-Engelman disease by Van Hul and colleagues [11], provides a timely update on the pathogenesis and management of this rare disease caused by mutations of the TGFB1 gene, which prevent the so-called LAP region of the protein binding to the mature TGFβ1 peptide thereby causing activation of TGFβ1 signaling. As the authors explain, corticosteroid therapy seems to be the only effective treatment for this condition at present, but there is some hope that the promising results that have been achieved with TGF receptor antagonists in animal models might eventually be translated into clinical practice.…”