Camurati-Engelmann disease

Bone is constantly remodelled, with old bone broken down and new bone laid down. In Camurati-Engelmann disease, which is also known as progressive diaphyseal dysplasia, this balance tips towards too much new bone. The shafts of the long bones in the arms and legs become thickened, and the skull base and vault can thicken as well.

MedlinePlus Genetics notes that the cause is a change in the TGFB1 gene. This gene makes transforming growth factor beta-1, a signalling protein that regulates many tissues, and the altered version is overactive, so it drives excessive bone formation throughout the skeleton.

Experience differs widely, even within one family. NORD lists limb pain, a waddling gait, muscle weakness and marked tiredness. Pain can range from mild to severe, and joint deformities, flat feet, scoliosis and joint contractures can occur. Symptoms typically emerge in childhood or adolescence, with pain and muscle weakness established by the teenage years.

When the skull is thickened, the head may look enlarged, with a prominent forehead and protruding eyes. In roughly one in four people, MedlinePlus Genetics says, raised pressure inside the skull causes headaches, hearing loss, vision problems, dizziness, ringing in the ears and facial weakness. This happens because nerves leaving the skull are squeezed as the openings narrow.

• Aching or sharp pain in the thighs and lower legs, often worse with activity.

• Tiredness and weak thigh and calf muscles that slow walking.

• A characteristic waddling gait.

• Headache, hearing loss, tinnitus, dizziness or facial weakness if the skull is involved.

• Some carriers have no symptoms at all, because of reduced penetrance.

NORD explains that doctors identify the condition through examination and X-rays, which show thickening of the shafts of the long bones and of the base of the skull. Molecular testing can confirm a change in the TGFB1 gene.

Because the condition is rare, many people spend time under general orthopaedic, rheumatology or paediatric care before the pattern is recognised. In the UK a GP or paediatrician can refer to a metabolic bone or clinical genetics service, which can arrange a skeletal survey, blood tests to rule out other bone disorders and genetic testing. Conditions that thicken bone in other ways, such as fibrous dysplasia or Paget disease of bone, need to be distinguished.

There is no treatment that corrects the underlying gene change, so care is directed at symptoms. NORD states that corticosteroids and non-steroidal anti-inflammatory drugs are used for pain, while long-term corticosteroids bring side effects that have to be weighed. Losartan has shown promise in reducing pain and improving muscle strength in some people, but formal studies are limited, so it is not a standard treatment everywhere.

Decompression surgery to widen the narrowed openings of the skull may be considered for hearing loss, although NORD notes that results vary. Physiotherapy helps maintain strength and walking, and occupational therapy and aids can reduce the strain of daily tasks. Pain, hearing and vision specialists often work together.

Camurati-Engelmann disease follows an autosomal dominant pattern, so one altered copy of TGFB1 is enough. MedlinePlus Genetics says that some people inherit the change from an affected parent while others have a new variant, and that some carriers never develop symptoms. An affected parent has a 50% chance of passing the change on in each pregnancy, according to NORD.

Because penetrance is incomplete, finding the variant in a relative does not predict whether or how severely they will be affected. Genetic counselling is the right place to talk through testing for children and relatives, and options during a future pregnancy.

Pacing activity, regular gentle exercise, good footwear for flat feet and a review of pain medicines all help. Sleep, mood and fatigue deserve attention, because chronic pain in young people can affect school and confidence.

Arrange a prompt review for new or worsening hearing loss, ringing in the ears, double or blurred vision, persistent severe headache, dizziness or facial weakness, as these can reflect nerve compression. Sudden loss of hearing or vision, or sudden facial drooping with other stroke signs, needs urgent assessment through NHS 111 or 999. Because the condition is lifelong and very rare, it helps to keep a copy of your diagnosis and key reports for any new clinician.