Clinical diagnosis and mutation analysis of a Chinese family with Camurati-Engelmann disease

Abstract

Camurati-Engelmann disease (CED) is a rare autosomal dominant bone disorder caused by a mutation in transforming growth factor β1 (TGFβ1). The present study aimed to identify a Chinese family with suspected CED based on the clinical symptoms, including pain in extremities, waddling gait, muscle weakness, cortical thickening of the diaphysis of the long bones, and sclerosis of the skull, facial bone, and pelvis. Molecular analysis revealed the presence of the p.Glu169Lys (E169K) mutation in exon 2 of TGFβ1 in patients when compared with the controls. Therefore, the Chinese family was diagnosed with CED due to the presence of the E169K mutation. The present study emphasized the importance of clinical and genetic evidence for the diagnosis of CED. The data presented in the present study are of significance to clinicians, as well as genetic counselors, in the prenatal screening of CED.

Clinical characteristics and treatment outcomes in Camurati–Engelmann disease

“…Sequence analysis of TGFB1 identified p.Arg218His, p.Arg218Cys, and p.Glu169Lys mutations, all of which were previously reported as pathogenic. [ 14 , 15 ]…”

Observations on the Natural History of Camurati-Engelmann Disease

“…Since then, genetic studies have led to an appreciation of a wide, but as yet unexplained, variability in the phenotype even within families with the same TGFB1 gene mutation. In terms of symptoms, the disease spectrum can vary from young children who are severely affected, to young adults with cranial nerve palsies (resulting from hyperostosis of the skull), through to adults who are minimally symptomatic . Sequential skeletal radiographs over periods of 1 to 32 years demonstrated worsening disease in less than one‐half the members of a large Israeli kindred, raising the question as to whether the disease is indeed always progressive.…”

“…This is best assessed by skeletal scintigraphy, which is a test that primarily reflects physiological or pathological increases in bone turnover . Information on skeletal scintigraphy is absent or patchy in the great majority of reports of large CED kindreds with proven TGFB1 gene mutations …”

“…In terms of symptoms, the disease spectrum can vary from young children who are severely affected, to young adults with cranial nerve palsies (resulting from hyperostosis of the skull), through to adults who are minimally symptomatic. (5,(7)(8)(9)(10)(11)(12) Sequential skeletal radiographs over periods of 1 to 32 years demonstrated worsening disease in less than one-half the members of a large Israeli kindred, (13) raising the question as to whether the disease is indeed always progressive. To add to this complexity, there are descriptions of patients whose symptoms seem to resolve with age, (6)(7)(8) and one case of a mutation carrier with no clinical or radiographic evidence of disease.…”

“…(6) Information on skeletal scintigraphy is absent or patchy in the great majority of reports of large CED kindreds with proven TGFB1 gene mutations. (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) In an extended kindred affected with CED 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.…”