Simsek S, Janssens K, Kwee M L, Van Hul W, Veenstra J, Netelenbos J C
Department of Endocrinology/Diabetes Center, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Osteoporos Int. 2005 Sep;16(9):1167-70. doi: 10.1007/s00198-005-1896-2. Epub 2005 Jun 16.
We report on a 46-year-old mother of Moroccan origin, suffering mainly from painful, swollen legs, and her 26-year-old son who had experienced intense pain in his legs, without fever, for approximately 3 years. They did not have dysmorphic features or abnormal gaits. Radiographic studies of the mother revealed diaphyseal sclerosis of the tibia and spondylosis of the thoracal and lumbar vertebrae. The son had sclerosis of the diaphyses of the metacarpalia of the left hand, the femur and the fibula. The other parts of the skeleton were normal. Several osteosclerotic/hyperostotic disorders, such as melorheostosis (present mostly in sporadic cases and affecting lower extremities) and van Buchem's disease (autosomal recessive and commonly affecting the mandible) were considered as a diagnosis in the proposita. However, similar symptoms in the son of the proposita suggested an autosomal dominant inheritance pattern. This brought us to the diagnosis of progressive diaphyseal dysplasia (PDD) or Camurati-Engelmann disease (CED), an autosomal dominant disorder characterized by limb pain, reduced muscle mass, weakness, a waddling gait, progressive periosteal and endosteal sclerosis of the diaphyses of the long bones and sclerosis of the skull base. Mutations in the transforming growth factor (TGF)-beta1 gene on chromosome 19q13.1 have been reported to cause this disorder. The diagnosis of PDD/CED in this family was confirmed at the molecular level by detection of a C-to-T transition at position 466, leading to an arginine-to-cysteine amino acid change (position 156) in exon 2 of the transforming growth factor-beta1 (TGFB1) gene.
我们报告了一位46岁、来自摩洛哥的母亲，她主要患有腿部疼痛和肿胀，以及她26岁的儿子，他腿部剧烈疼痛约3年，无发热症状。他们没有畸形特征或异常步态。对母亲的影像学检查显示胫骨骨干硬化以及胸椎和腰椎脊柱关节病。儿子左手掌骨、股骨和腓骨骨干有硬化。骨骼的其他部位正常。几种骨硬化/骨质增生性疾病，如肢骨纹状肥大（大多为散发病例，主要影响下肢）和范布赫姆病（常染色体隐性遗传，通常影响下颌骨），都被考虑作为先证者的诊断。然而，先证者儿子的类似症状提示常染色体显性遗传模式。这使我们诊断为先证者患有进行性骨干发育异常（PDD）或卡穆拉蒂 - 恩格尔曼病（CED），这是一种常染色体显性疾病，其特征为肢体疼痛、肌肉量减少、无力、蹒跚步态、长骨骨干渐进性骨膜和骨髓硬化以及颅底硬化。据报道，位于19q13.1染色体上的转化生长因子（TGF）-β1基因的突变可导致这种疾病。通过检测转化生长因子-β1（TGFB1）基因外显子2中第466位的C到T转换，导致第156位氨基酸由精氨酸变为半胱氨酸，在分子水平上证实了该家族中PDD/CED的诊断。
