Observations on the Natural History of Camurati-Engelmann Disease

Abstract

Camurati‐Engelmann disease (OMIM 31300) is a rare cranio‐tubular bone dysplasia characterized by osteosclerosis of the long bones and skull caused by dominantly‐inherited mutations in the transforming growth factor beta 1 (TGFB1) gene. A wide variation in phenotype has been recognized, even within families carrying the same mutation. In addition, aspects of the natural history of the disorder, in particular whether it is always progressive or can remit spontaneously, remain uncertain. In a large kindred carrying a TGFB1 gene mutation (c.653G > A; p.R218H) we have attempted to clarify the extent of phenotypic variability and the natural history of the disease through detailed individual histories of symptoms, and skeletal imaging by both radiography and scintigraphy. Only one subject had the classical childhood onset with bone pain in the legs and gait disturbance. Eight subjects reported the onset of leg pain in their teenage years that, by their early 20s, had either resolved or persisted at a low level. Two of these eight later developed cranial nerve palsies. There was a wide variation in the radiographic appearance in adults, but disease extent and activity in long bones, as assessed by scintigraphy, was inversely correlated with age (p < 0.025). In younger subjects the radiographic and scintigraphic appearances were concordant, but in older subjects the scintigram could be quiescent despite florid radiographic changes. Sequential scintigrams in two subjects showed reduced activity in the later scan. One subject had suffered meningoencephalitis in early childhood that resulted in paresis of one arm. The affected arm showed markedly less disease involvement, implicating mechanical or growth factors in its etiology. Our data suggest that the natural history of Camurati‐Engelmann disease can be benign, and that disease activity commonly attenuates in adulthood. Severe cases of childhood onset and/or with cranial nerve involvement, may occur only in a minority of mutation carriers. © 2019 American Society for Bone and Mineral Research.

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

“…In addition, II8 in Family 1showed typical PDD symptoms in childhood, whereas she recovered from bone pain at the age of 30 without any treatment. This spontaneous remission was in accordance with the previous studies [9,21]. Our study indicated that the decreased concentration of TGF-β1 with aging may contribute to this condition [22,23].…”

“…The above variant clinical manifestations may be closely related to post-translational modi cation and other regulatory factors, and mechanical stimulation may also play a partial role [9,20]. Previous study in large pedigrees had described a tendency of PDD to occur earlier and more severe in the younger generations [7,11,12], which was genetically named "anticipation".…”

“…Some cases have systemic manifestations or like some kind of syndromes, accompanied with anemia, leukopenia and hepatosplenomegaly for instance [5]. Since PDD is a kind of rare disease, to date, there are altogether 300 cases with PDD have been reported over the world [4,[6][7][8][9][10][11][12]. Therefore, the diagnosis of PDD is a great challenge for clinicians owing to its rarity and extensive phenotypic variations.…”

Whole‐Body Magnetic Resonance Imaging in Camurati–Engelmann Disease

“…We commend Hughes and colleagues (1) for their study entitled "Observations on the Natural History of Camurati-Engelmann Disease", published in the Journal of Bone and Mineral Research. In this study, 10 members of a family carrying a common TGFB1 gene mutation had their symptoms evaluated and both skeletal radiographs and scintigraphies performed.…”

Enfermedad de Camurati-Engelmann

“…analizaron 10 casos de una familia de Nueva Zelanda (la mitad eran asintomáticos), encontrando la mutación R218H en el gen TGFB1. 8 En Colombia, Vega-Caicedo y su equipo reportaron un paciente de 11 años con hallazgos radiológicos y clínicos sugestivos de la enfermedad, con una fractura patológica subtrocantérica como complicación. 9 También, Restrepo y cols.…”