Camurati-Engelmann disease

Camurati-Engelmann disease (CED) is an inherited bone dysplasia in which the shafts of the long bones, skull, spine, and pelvis become abnormally thick and dense. Variants in the TGFB1 gene disrupt a signaling pathway that normally regulates bone growth, leading to excessive bone formation and inflammation in the surrounding tissues. Symptoms usually begin in childhood or adolescence and affect males and females equally. The condition is considered very rare, affecting fewer than one in a million people worldwide. Because severity and symptoms vary widely between individuals, age at diagnosis and daily impact can differ even within the same family.

Persistent limb pain, especially in the lower legs, is the most common early sign and is often severe enough to limit daily activity. Many children develop a wide-based waddling gait as thickened bones alter the shape of the hips and legs. Over time, progressive cortical thickening of the long bones, skull, and spine can lead to joint stiffness, muscle weakness, and easy fatigability. Some individuals experience additional features such as proptosis due to skull changes, hearing impairment from narrowing of the ear canals, or curvature of the spine (scoliosis). A small number develop anemia, likely related to reduced bone marrow space. Not all individuals experience all features, and severity can range from mild discomfort to significant disability.

CED is caused by pathogenic variants in the TGFB1 gene. TGFB1 encodes transforming growth factor-beta 1, a protein that controls how bone is formed and remodeled. When this signaling pathway is overactive, bone tissue accumulates in places it normally would not, causing the characteristic thickening and associated pain. The condition is inherited in an autosomal dominant pattern, meaning one altered copy of TGFB1 is sufficient to cause disease. Each child of an affected individual has a 50 percent chance of inheriting the variant. Even within the same family, the severity and specific symptoms can vary considerably, a phenomenon known as variable expressivity. Genetic counseling is recommended for families to understand inheritance and reproductive options.

Currently, management focuses on supportive care and symptom relief. Pain is typically addressed with anti-inflammatory medications, physical therapy to maintain mobility, and in some cases assistive devices to reduce joint stress. Because CED can affect several body systems, care is best provided by a multidisciplinary team that may include orthopedic specialists, physiotherapists, pain management experts, and audiologists. Long-term management includes regular surveillance to monitor bone changes, evaluate hearing, and assess spine alignment so that complications can be addressed promptly. Patients should discuss specific treatment plans and monitoring schedules with their healthcare team to determine what is appropriate for their situation, and genetic counseling can guide family members who may be at risk.

The long-term outlook for individuals with Camurati-Engelmann disease varies widely. Some people maintain an active lifestyle with modest limitations, while others experience persistent pain and mobility challenges that require ongoing support. Outcomes described in medical literature continue to evolve as standards of care improve. Regular follow-up with knowledgeable specialists and early intervention for complications can help many individuals preserve function and quality of life. Families often find it helpful to connect with genetic counselors and multidisciplinary clinics experienced in managing complex bone disorders.

Several clinical trials are currently investigating new treatments aimed at modulating the TGFB1 pathway or reducing bone pain and inflammation. Individuals interested in participating in research can search ClinicalTrials.gov or consult their care team about eligibility.