Camurati-Engelmann disease is a genetic condition that mainly affects the bones. People with this disease have increased bone density, particularly affecting the long bones of the arms and legs. In some cases, the skull and hip bones are also affected. The thickened bones can lead to pain in the arms and legs, a waddling walk, muscle weakness, and extreme tiredness. The age that symptoms begin varies greatly, but most people with this condition develop pain or weakness by adolescence.

Camurati-Engelmann disease is caused by a mutation in the TGFB1 gene and inheritance is autosomal dominant. In some cases, people have the gene mutation that causes Camurati-Engelmann disease but they never develop symptoms. In others, symptoms are present, but a gene mutation cannot be found. These cases are referred to as Camurati-Engelmann disease type 2.

Treatment for Camurati-Engelman disease depends on many factors including the signs and symptoms present in each person and the severity of the condition. Treatment options to control symptoms may include corticosteroid therapy, losartan as an adjuvant therapy to minimize the need for steroids, pain medications, and craniectomy to reduce intracranial pressure and headaches.

People with Camurati-Engelmann disease have increased bone density, particularly affecting the long bones of the arms and legs (tibia, femur, humerus, ulna, radius). In some cases, the skull and hip bones are also affected. The thickened bones can lead to pain in the arms and legs, a waddling walk, muscle weakness, and extreme tiredness. An increase in the density of the skull results in increased pressure on the brain and can cause a variety of neurological problems, including headaches, hearing loss, vision problems, dizziness (vertigo), ringing in the ears (tinnitus), and facial paralysis. The added pressure that thickened bones put on the muscular and skeletal systems can cause abnormal curvature of the spine (scoliosis), joint deformities (contractures), knock knees, and flat feet (pes planus). Other features of Camurati-Engelmann disease include abnormally long limbs in proportion to height, a decrease in muscle mass and body fat, and delayed puberty. In the most severe cases, the mandibula (jaw), vertebrae, thoracic cage, shoulder girdle, and carpal (hands, wrist) and tarsal (foot, ankle) bones are involved.

Radiographically (on X-ray), the shafts of long bones show symmetric and progressive widening and malformation (diaphyseal dysplasia). Vascular (Raynaud's phenomenon) and hematological (anemia, leukopenia (low level of white blood cells), increased erythrocyte sedimentation rate) features and hepatosplenomegaly are commonly associated with the disease.

The age at which affected individuals first experience symptoms varies greatly; however, most people with this condition develop pain or weakness by adolescence.

Mutations in the TGFB1 gene cause Camurati-Engelmann disease. The TGFB1 gene provides instructions for producing a protein called transforming growth factor beta-1 (TGFβ-1). The TGFβ-1 protein helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). The TGFβ-1 protein is found throughout the body and plays a role in development before birth, the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. TGFβ-1 is particularly abundant in tissues that make up the skeleton, where it helps regulate bone growth, and in the intricate lattice that forms in the spaces between cells (the extracellular matrix).

Within cells, the TGFβ-1 protein is turned off (inactive) until it receives a chemical signal to become active. The TGFB1 gene mutations that cause Camurati-Engelmann disease result in the production of a TGFβ-1 protein that is always turned on (active). Overactive TGFβ-1 proteins lead to increased bone density and decreased body fat and muscle tissue, contributing to the signs and symptoms of Camurati-Engelmann disease.

Some individuals with Camurati-Engelmnan disease do not have identified mutations in the TGFB1 gene. In these cases, the cause of the condition is unknown.

Diagnosis of Camurati-Engelmann disease is based on physical examination and radiographic findings and can be confirmed by molecular genetic testing. TGFB1 is the only gene known to be associated with Camurati-Engelmann disease. Sequence analysis identifies mutations in TGFB1 in about 90% of affected individuals and is clinically available.

Individuals with a family history of Camurati-Engelmann disease or symptoms associated with this condition may wish to consult with a genetics professional. Visit the Find a Specialist section on this page to learn how you can locate a genetics professional in your community.

Treatment for Camurati-Engelmann disease depends on the symptoms and severity in each person. Several medications, including corticosteroids, biphosphonates, and non-steroidal anti-inflammatory drugs (NSAIDs), have been used to manage the symptoms of Camurati-Engelmann disease (CED). NSAIDs and bisphosphonates have not been proven to be effective for most people with CED. Corticosteroids may relieve some of the symptoms such as pain and weakness, and can also improve gait and exercise tolerance. However, they have serious side effects with long-term use.

More recently, losartan, an angiotensin II type 1 receptor antagonist, has been reported to reduce limb pain and increase muscle strength in multiple case reports. However, the use of losartan needs more study to determine if it is effective and safe for those with CED. Exercise programs, when tolerated, have also been found to be beneficial.

Surgical procedures may also be needed in people with CES. Craniectomy, which involves removing a portion of the skull to relieve pressure on the brain, may be needed to reduce intracranial pressure and relieve symptoms in some people. Myringotomy, a procedure used to relieve pressure within the middle ear, may improve conductive hearing loss from fluid build-up in the ear.

Ongoing surveillance by various specialists may be needed to monitor signs and symptoms and make sure medical therapies remain safe to use. Depending on each person's symptoms and treatment, a person with CES may need periodic blood pressure checks, blood tests, neurologic exams, hearing evaluations, eye exams, bone density scans, or other types of surveillance. Children with CES should have routine growth monitoring, and those with cranial involvement (including those treated surgically) should continue to be monitored for signs and symptoms of increased intracranial pressure.

Please note: Case reports detail the signs and symptoms in individual cases. It is important to keep in mind that the features documented in these case reports are based on specific individuals and may not necessarily apply to others with the same disease.

Around half of people with Camurati-Engelmann disease have skull base thickening and around one-fourth of these people develop symptoms. Symptoms may be constant or come and go. Some patient's symptoms stabilize, while other's worsen with time. Signs and symptoms reported in the medical literature, include;

• Hearing loss
• Headache
• Bulging eyes
• Prominent forehead

Less common signs and symptoms, include;

• Vision changes
• Vertigo
• Facial weakness
• Symptomatic brain stem compression
• Facial numbness
• Loss of smell

Treatment of symptoms due to skull base thickening may involve aggressive decompression surgery in carefully selected patients. Corticosteroids and bisphosphates that may improve symptoms in the arms, legs, and torsos of some patients, have not been shown to improve symptoms caused by skull base thickening. Decompression surgery is challenging and patients are at an increased risk for complications with surgery. The form of decompression surgery will vary depending on the skull involvement and symptoms experienced by the patient. Likewise the risks for complications vary depending on these factors.

Following surgery it is possible for the bone to regrow. A recent review article found that 3 of 28 cases reported in the literature described bony regrowth following decompression surgery.