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Diseases

Genetic and Rare Diseases Information Center (GARD)

Camurati-Engelmann disease


Other Names for this Disease
  • CED
  • Diaphyseal dysplasia 1, progressive
  • DPD1
  • Engelmann disease
  • Progressive diaphyseal dysplasia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

My mother-in-law was recently diagnosed with Camurati-Engelmann disease. Can you provide me with information about this condition?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is Camurati-Engelmann disease?

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 at which affected individuals first experience symptoms varies greatly; however, most people with this condition develop pain or weakness by adolescence.[1]

Camurati-Engelmann disease is caused by a mutation in the TGFB1 gene which is inherited in an autosomal dominant fashion.[1][2] In some instances, people have the gene mutation that causes Camurati-Engelmann disease but never develop the characteristic features of this condition.[1] In others, features are present, but a mutation cannot be identified. These cases are referred to as Camurati-Engelmann disease type II.[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.[3]  
Last updated: 3/15/2016

What are the symptoms of Camurati-Engelmann disease?

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.[1][2] In the most severe cases, the mandibula (jaw), vertebrae, thoracic cage, shoulder girdle, and carpal (hands, wrist) and tarsal (foot, ankle) bones are involved.[4]

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.[2][4]

The age at which affected individuals first experience symptoms varies greatly; however, most people with this condition develop pain or weakness by adolescence.[1]
Last updated: 3/15/2016

What causes Camurati-Engelmann disease?

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).[1]

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.[1]

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.[1]

Last updated: 3/15/2016

How is Camurati-Engelmann disease diagnosed?

Diagnosis of Camurati-Engelmann disease is based on physical examination and radiographic findings and can be confirmed by molecular genetic testingTGFB1 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.[3]

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  Genetic Resources section to learn how you can locate a genetics professional in your community.
Last updated: 3/15/2016

How is Camurati-Engelmann disease inherited?

Camurati-Engelmann disease is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.[1][2][3]

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.
Last updated: 3/15/2016

How might Camurati-Engelmann disease (CED) be treated?

Several medical therapies 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 corticosteroids have serious side effects with long term use.[2][3][5][6][7]

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.[6][7] However, the effectiveness of losartan needs more study to determine if it is effective for those with CED and without major side effects. Exercise programs when they are tolerated have also been found to be beneficial.[6][7]

Please note, case reports report the clinical findings associated with individual cases. It is important to keep in mind that the clinical findings documented in these case reports are based on specific individuals and may differ from one affected person to another.
Last updated: 3/15/2016

References
Other Names for this Disease
  • CED
  • Diaphyseal dysplasia 1, progressive
  • DPD1
  • Engelmann disease
  • Progressive diaphyseal dysplasia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.