Camurati-Engelmann disease

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Camurati-Engelmann disease is a skeletal condition that is characterized by abnormally thick bones (hyperostosis) in the arms, legs, and skull.

The thick limb bones can lead to bone pain and muscle weakness in the arms and legs and cause individuals with Camurati-Engelmann disease to tire quickly. Bone pain ranges from mild to severe and can increase with stress, activity, or cold weather. Leg weakness can make it difficult to stand up from a seated position and some affected individuals develop a waddling or unsteady walk. Additional limb abnormalities include joint deformities (contractures), knock knees, and flat feet (pes planus). Swelling and redness (erythema) of the limbs and an abnormal curvature of the spine can also occur.

Individuals with Camurati-Engelmann disease may have an unusually thick skull, which can lead to an abnormally large head (macrocephaly) and lower jaw (mandible), a prominent forehead (frontal bossing), and bulging eyes with shallow eye sockets (ocular proptosis). These changes to the head and face become more prominent with age and are most noticeable in affected adults. In about a quarter of individuals with Camurati-Engelmann disease, the thickened skull increases pressure on the brain or compresses the spinal cord, which can cause a variety of neurological problems, including headaches, hearing loss, vision problems, dizziness (vertigo), ringing in the ears (tinnitus), and facial paralysis.

The degree of hyperostosis varies among individuals with Camurati-Engelmann disease as does the age at which they experience their first symptoms.

Other, rare features of Camurati-Engelmann disease include abnormally long limbs in proportion to height, a decrease in muscle mass and body fat, delayed teething (dentition), frequent cavities, delayed puberty, a shortage of red blood cells (anemia), an enlarged liver and spleen (hepatosplenomegaly), thinning of the skin, and excessively sweaty (hyperhidrotic) hands and feet.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

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 triggers chemical signals that regulate various cell activities, including the growth and division (proliferation) of cells, the maturation of cells to carry out specific functions (differentiation), cell movement (motility), and controlled cell death (apoptosis).

The TGFβ-1 protein is found throughout the body but is particularly abundant in tissues that make up the skeleton, where it helps regulate the formation and growth of bone and cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. TGFβ-1 is involved in different processes in other tissues.

The TGFB1 gene mutations that cause Camurati-Engelmann disease result in the production of an overly active TGFβ-1 protein. This abnormal TGFβ-1 protein activity causes an increase in signaling, which leads to more bone formation. As a result, the bones in the arms, legs, and skull are thicker than normal, contributing to the movement and neurological problems often experienced by individuals with Camurati-Engelmann disease.

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

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Some people who have the altered gene never develop the condition, a situation known as reduced penetrance.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of Camurati-Engelmann disease is unknown. More than 300 cases have been reported worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal diaphysis morphology · Very frequent (99-80%)

An abnormality of the structure or form of the diaphysis, i.e., of the main or mid-section (shaft) of a long bone.

Abnormal humerus morphology · Very frequent (99-80%)

Any structural anomaly of the structure of the humerus (i.e., upper arm bone).

Abnormal morphology of the radius · Very frequent (99-80%)

An abnormality of the radius.

Abnormal morphology of ulna · Very frequent (99-80%)

Any structural anomaly of the ulna, a bone of the forearm the extends from the elbow to the little finger.

Abnormal skull morphology · Very frequent (99-80%)

An abnormality of the skull, the bony framework of the head which is comprised of the neurocranium (with eight cranial bones) and the viscerocranium (facial skeleton) that comprises fourteen facial bones with the mandible as its largest bone.

Abnormality of femur morphology · Very frequent (99-80%)

Any anomaly of the structure of the femur.

Abnormality of the vertebral column · Very frequent (99-80%)

Any abnormality of the vertebral column.

Aplasia/Hypoplasia of the radius · Very frequent (99-80%)

A small/hypoplastic or absent/aplastic radius.

Other findings in the same source

From: Orphanet

Additional reported features include Bone pain (Very frequent (99-80%)); Cachexia (Very frequent (99-80%)); Cortical thickening of long bone diaphyses (Very frequent (99-80%)); Craniofacial osteosclerosis (Very frequent (99-80%)); Elevated circulating aldolase concentration (Very frequent (99-80%)); Hyperostosis (Very frequent (99-80%)); Skeletal dysplasia (Very frequent (99-80%)); Abnormality of tibia morphology (Frequent (79-30%)); Limitation of joint mobility (Frequent (79-30%)); Metaphyseal dysplasia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Camurati-Engelmann disease is Orthopaedics, with a orthopaedic specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What explains the change in pain, movement or function?
• Which activities need adjustment while the diagnosis is being clarified?
• What are the roles of rehabilitation, observation and surgery in this situation?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Camurati-Engelmann disease. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.