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Disease Profile

Camurati-Engelmann disease

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset






Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

CED; Diaphyseal dysplasia 1, progressive; DPD1;


Congenital and Genetic Diseases; Musculoskeletal Diseases


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.[1]

Camurati-Engelmann disease is caused by a mutation in the TGFB1 gene and inheritance is autosomal dominant.[1][2] In some cases, people have the gene mutation that causes Camurati-Engelmann disease but they never develop symptoms.[1] In others, symptoms are present, but a gene mutation cannot be found. These cases are referred to as Camurati-Engelmann disease type 2.[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] 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.[3]


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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Abnormality of the humerus
Abnormality of the ulna
Aplasia/Hypoplasia of the radius
Bone pain
Wasting syndrome
Cortical thickening of long bone diaphyses
Craniofacial osteosclerosis
Elevated aldolase level
Bone overgrowth
30%-79% of people have these symptoms
Abnormality of tibia morphology
Abnormality of the shankbone
Abnormality of the shinbone

[ more ]

Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

Metaphyseal dysplasia
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

Waddling gait
Waddling walk
'Waddling' gait

[ more ]

5%-29% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
Abnormal subcutaneous fat tissue distribution
Abnormal fat tissue distribution below the skin
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
Low number of red blood cells or hemoglobin
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

Coxa valga
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

Elevated erythrocyte sedimentation rate
High ESR
Facial palsy
Bell's palsy
Feeding difficulties in infancy
Frontal bossing
Genu valgum
Knock knees
Hearing impairment
Hearing defect

[ more ]

Enlarged liver
Prominent swayback
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
Decreased activity of gonads
Hunched back
Round back

[ more ]

Decreased blood leukocyte number
Low white blood cell count

[ more ]

Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

Optic atrophy
Optic nerve compression
Pes planus
Flat feet
Flat foot

[ more ]

Protruding eyes
Prominent globes
Prominent eyes
Eyeballs bulging out
Bulging eye

[ more ]

Sensory neuropathy
Damage to nerves that sense feeling
Slender build
Thin build
Increased spleen size
Urinary retention
1%-4% of people have these symptoms
Easy fatigability
Limb pain
Lower limb pain
Leg pain
Muscle weakness
Muscular weakness
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
Bone marrow hypocellularity
Bone marrow failure
Diaphyseal sclerosis
Increased bone density in shaft of long bone
Double vision


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]


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 GeneTGFB1 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 Find a Specialist section on this page to learn how you can locate a genetics professional in your community.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    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.[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 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.[6][7]

    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.[3]

    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.[3]

    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.


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Social Networking Websites

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Camurati-Engelmann disease. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Camurati-Engelmann disease. Click on the link to view a sample search on this topic.


          1. Camurati-Engelmann disease. Genetics Home Reference. November, 2017; https://ghr.nlm.nih.gov/condition/camurati-engelmann-disease.
          2. Camurati-Engelmann disease. Orphanet. November 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=1328.
          3. Wallace SE and Wilcox WR. Camurati-Engelmann Disease. GeneReviews. October 12, 2017; https://www.ncbi.nlm.nih.gov/books/NBK1156/.
          4. Camurati-Engelmann Disease. National Organization for Rare Disorders (NORD). 2007; https://rarediseases.org/rare-diseases/camurati-engelmann-disease/.
          5. de Bonilla Damiá Á and García Gómez FJ. Camurati-Engelmann disease. Reumatol Clin. Jan 29, 2016; https://www.ncbi.nlm.nih.gov/pubmed/26830437.
          6. Ayyavoo A, Derraik JG, Cutfield WS, and Hofman PL. Elimination of pain and improvement of exercise capacity in Camurati-Engelmann disease with losartan. J Clin Endocrinol Metab. November 2014; 99(11):3978-82. https://www.ncbi.nlm.nih.gov/pubmed/25140400.
          7. Simsek-Kiper PO, Dikoglu E, Campos-Xavier B, Utine GE, Bonafe L, Unger S, Boduroglu K, and Superti-Furga A. Positive effects of an angiotensin II type 1 receptor antagonist in Camurati-Engelmann disease: A single case observation. Am J Med Genet Part A. 2014; 9999:2667–2671. https://www.ncbi.nlm.nih.gov/pubmed/25099136.

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