Phenotypic Variability in Camurati–Engelmann Disease: A Case Report of a Family with the c.653G>A Pathogenic Variant in the TGFB1 Gene

Abstract

Camurati–Engelmann Disease (CED), or Progressive Diaphyseal Dysplasia, is a rare autosomal dominant disorder caused by heterozygous mutations in the TGFB1 Gene, essential for bone regeneration. This study examines the genotype–phenotype relationship in a family diagnosed with CED, specifically focusing on a missense variant (c.653G>A, p.Arg218Cys). The family comprised a mother and her two children, all of whom were found to carry the same disease-causing variant. The second child exhibited severe symptoms by age six, including progressive weakness and joint pain, leading to wheelchair dependency. The mother displayed milder symptoms with preserved independence. The firstborn son, initially asymptomatic, developed gait abnormalities and pain during adolescence. Clinical evaluations revealed characteristic hyperostosis of long bones, with significant variability in symptom onset and severity among family members, potentially indicative of genetic anticipation. This case underscores the importance of genetic testing and interdisciplinary management in CED, as traditional treatments, including corticosteroids and NSAIDs, often yield limited efficacy and notable side effects. Our findings contribute to the understanding of CED’s pathophysiology and highlight the necessity for tailored therapeutic approaches. The identification of the common TGFB1 variant in this family reinforces the critical role of TGFB1 in bone metabolism and suggests avenues for further research into targeted therapies. Such reports enhance awareness and provide valuable insights for healthcare professionals managing rare genetic disorders.