Camurati-Engelmann's disease (also known as Engelmann’s Disease,
Engelmann’s Syndrome,
Progressive diaphyseal dysplasia,
Diaphyseal dysplasia,
CED) is a rare autosomal dominant disease which mainly affects the bones of the body.
There is hyperostosis particularly in the long bones of arms and legs,
and in the skull.
This increased bone density causes severe limb pain,
proximal muscle weakness and fatigability,
joint contractures,
and a wide-based,
waddling gait.
Involvement of the skull can lead to headache,
cranial nerve impingement (manifesting for example as facial palsy,
hearing loss,
visual deficit) as well as frontal bossing,
proptosis and prognathism.
Less common features include anaemia,
decreased subcutaneous fat,
marfanoid habitus,
delayed puberty and hypogonadism.
Periosteal and endosteal bony sclerosis of the diaphyses results in uneven cortical thickening,
increased diameter,
and occasionally in narrowing of the meducallary canal.
Hyperostosis is usually symmetrical.
Susceptibility to fractures may be reduced because of increased bone mineral density,
but healing of fractures once they occur may be delayed.
There are approximately 200 reported cases world-wide. Symptoms typically manifest in adolescence with progressive long bone pain and muscle weakness.
Diagnosis is based primarily on physical examination and radiographic findings (hyperostosis of one or more long bones).
Confirmation can be made by molecular genetic testing.
Mutation of the transforming growth factor beta-1 (TGFB-1) gene is found in about 90% of CED patients.
This codes for TGFB-1; a protein found throughout the body but which is particularly abundant in the skeleton.
Here it regulates the extracellular matrix,
thereby helping to control bone growth and resorption.
The CED mutation ‘turns on’ the normally dormant TGFB-1 gene,
leading to the progressive musculoskeletal dysplasia.
Corticosteroids have been shown to provide symptomatic treatment for pain relief and improvement of gait,
weakness and flexion contractures.
For severe acute exacerbations a daily bolus of prednisolone 1-2mg/kg is recommended.
This can then be rapidly tapered to the lowest dose tolerated,
preferably on alternate days (eg 0.5-1mg/kg).
There is some evidence that this may delay skull hyperostosis,
however long-term follow-up studies are lacking.
Losartan is used as adjuvant therapy or as second line therapy for steroid-intolerant patients,
or those with concomitant hypertension (anti-TGFB-1 properties).
Regular analgesics and non-pharmacological treatments such as physiotherapy and massage can provide additional symptomatic relief.