Camurati-Engelmann Disease

Clinical characteristics: Camurati-Engelmann disease (CED) is characterized by hyperostosis of the long bones and the skull, proximal muscle weakness, limb pain, a wide-based, waddling gait, and joint contractures. Facial features such as macrocephaly, frontal bossing, enlargement of the mandible, proptosis, and cranial nerve impingement resulting in facial palsy are seen in severely affected individuals later in life.

Diagnosis/testing: The diagnosis of CED is established in a proband with the characteristic radiographic findings or (if radiographic findings are inconclusive) a heterozygous pathogenic variant in TGFB1 identified by molecular genetic testing.

Management: Targeted therapy: Corticosteroid therapy as needed to control symptoms; losartan may be a helpful adjuvant therapy to minimize the need for steroids to control pain.

Supportive care: Management of muscle weakness and gait issues per physical medicine and rehabilitation specialists and physical therapist. Treatment of joint contractures and other musculoskeletal manifestations per orthopedist with experience in skeletal dysplasias; pain is also managed with analgesics, non-pharmacologic methods, and on occasion surgical treatment. Management of hearing loss per otolaryngologist; bilateral myringotomy can improve conductive hearing loss resulting from serous otitis. Treatment of ocular manifestations per ophthalmic subspecialist with low vision services as needed; craniectomy may be needed to reduce intracranial pressure and relieve symptoms in individuals with several cranial sclerosis. Adjustment of corticosteroids or losartan as needed for hyper- or hypotension; treatment with antihypertensives as needed; mobility assessment with adaptive devices and fall precautions.

Surveillance: Assess development of gross motor skills throughout childhood; assess for mobility issues, weakness, contractures, bone pain, and other musculoskeletal manifestations at each visit; serum ESR and bone scan as needed in those with acute bone pain to assess disease activity; evaluation of bone mineral density annually in those treated with corticosteroids; annual neurologic examination to assess for cranial nerve deficits and headaches; monitor for signs and symptoms of increased intracranial pressure at each visit; head and neck CT as needed in those with sclerosis of the skull base and neurologic symptoms to determine extent of disease and allow consideration of surgical treatment options; annual audiology evaluation with BAER and inner ear CT as needed; monitor linear growth and pubertal development at each visit throughout childhood; assess blood pressure at each visit; annual CBC.

Agents/circumstances to avoid: Excess phosphate.

Evaluation of relatives at risk: It is appropriate to evaluate relatives at risk in order to identify the diagnosis as early as possible, avoid potential misdiagnosis, and provide appropriate treatment for extremity pain.

Genetic counseling: CED is inherited in an autosomal dominant manner. Many individuals diagnosed with CED have an affected parent; some individuals diagnosed with CED may have the disorder as the result of a de novo TGFB1 pathogenic variant. Each child of an individual with CED has a 50% chance of inheriting the TGFB1 pathogenic variant. Once the TGFB1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for CED are possible.