Two cases of Camurati-Engelmann disease presenting as a neuromuscular disorder in early childhood

Abstract

  Camurati-Engelmann disease (MIM : 131300) is a rare autosomal dominant skeletal dysplasia characterized by cortical thickening and fusiform enlargement of the diaphysis of the long bones caused by gain-of-function variants in the transforming growth factor-β1 (TGFB1) gene. Most patients present with muscle weakness, waddling gait and easy fatigability in early childhood, followed by bone symptoms, such as limb pain, after adolescence. We report two boys who were initially suspected of having neuromuscular disease but were later diagnosed with Camurati-Engelmann disease in early childhood. Their perinatal courses and early gross motor development were normal. Both patients developed a waddling gait shortly after they achieved walking at the age of 12 and 14 months, respectively. They were referred to our hospital because they exhibited Gowers sign at the 3-year-old medical examination. Although serum CK values and electromyography were normal, routine skeletal muscle imaging studies (CT, MRI) revealed bone lesions. Plain X-ray of the lower limb demonstrated bone involvement characteristic of Camurati-Engelman disease. The diagnosis was confirmed by identification of a missense variant (NM_000660.7 : c.652C＞T [p.Arg218Cys], rs104894721) in the TGFB1 gene in both patients. In one patient, treatment with losartan was initiated at the age of 3 years, which improved exercise capacity. Camurati-Engelmann disease should be considered in children with proximal muscle weakness. When no specific neuromuscular disease can be identified in children with muscle weakness, physicians should perform skeletal muscle CT or MRI examination of lower limbs to evaluate the bone involvement.