Camurati-Engelmann disease (CED) is characterized by increased bone density primarily affecting the long bones of the arms and legs and the skull. The thickening of these bones leads to pain, a waddling gait, muscle weakness, and extreme fatigue. [rx]Increased density of the skull can cause a variety of neurological deficits such as headaches, hearing loss, vision problems, dizziness (vertigo), ringing in the ears (tinnitus), and even facial paralysis. The first symptoms of the condition can appear at varying ages, but usually during childhood, with pain and proximal muscle weakness developing by adolescence. CED is often diagnosed based on a physical exam and radiographic findings (X-rays). CED is inherited in an autosomal dominant manner and is caused by changes (mutations) in the TGFB1 gene.[rx]
Camurati-Engelmann Disease (CED) is a rare genetic disorder that affects the bones. In this article, we will simplify complex medical jargon and provide straightforward explanations of the types, causes, symptoms, diagnostic tests, treatments, and medications related to CED. Our goal is to make this information easily accessible and understandable.
Types of Camurati-Engelmann Disease:
- Classic CED: The most common form of CED, where bone abnormalities start in childhood or adolescence.
- Atypical CED: A rarer form with milder symptoms and a later onset.
Causes of Camurati-Engelmann Disease:
CED is primarily caused by mutations in the TGFB1 gene. This gene provides instructions for making a protein that regulates the growth and development of bones. When it’s mutated, bone remodeling becomes imbalanced, leading to the characteristic symptoms of CED.[rx]
CED is caused by mutations in TGFB1 which encodes transforming growth factor beta-1 protein. This protein helps control the growth and proliferation of cells, the process by which the cells mature and begin to specify (differentiate), cell movement, and cell directed self-destruction (apoptosis). The specific protein plays a huge role during prenatal development in the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. The protein is most abundant in skeletal tissue and the extracellular matrix that provides structural support and nutrients to the surrounding cells.[rx]
Normally, TGFB1 is inactive until a chemical signal is sent to turn it on. TGFB1 mutations that cause CED result in the gene being always turned on and active. This leads to increased bone density and decreased fat and muscle tissue, contributing to the symptoms listed above. Most individuals with CED have a TGFB1 mutation identified on molecular genetic testing, but some affected individuals do not.[rx]
CED is inherited as an autosomal dominant condition. This occurs when only a single copy of the mutated gene is needed to cause a specific disorder. The altered gene can be inherited from either parent, or can be a new mutation in the affected individual. The risk of transmitting the disease to the offspring of an affected parent is 50%, and is the same for males and females. Rarely, the disease can come from a spontaneous genetic mutation in the egg or sperm cell. In these people, the disease isn’t inherited from the one of the parents, but the individual can still pass it to their offspring.[rx]
Symptoms of Camurati-Engelmann Disease:
The first signs and symptoms of CED are usually limb pain, a waddling gait, muscle weakness, and extreme tiredness. If the bones at the base of the skull are affected, the individual may experience headaches, hearing loss, vision problems, vertigo, tinnitus, and even facial paralysis.[rx] Additional musculoskeletal features include scoliosis, joint contractures, knock knees, and flat feet. The individual may also present with abnormally long limbs in proportion to the height of their body, a decrease in muscle mass and body fat, visible prominence of the long bones in the legs, and rarely delayed puberty. While the first signs and symptoms can appear at varying ages, most appear during childhood or adolescence.[rx]
- Leg Pain: Persistent, deep-seated pain in the legs, often the first symptom.
- Muscle Weakness: Weakness in the muscles, making physical activities challenging.
- Waddling Gait: An unusual way of walking characterized by a swaying motion.
- Bone Thickening: Thickening of the bones, especially in the limbs and skull.
- Fatigue: Constant tiredness and low energy levels.
- Vision Problems: Rarely, CED can affect the eyes and cause vision impairment.
- Hearing Loss: In some cases, hearing difficulties may occur due to bone changes in the ear.
- Joint Stiffness: Stiffness and limited range of motion in the joints.
- Delayed Puberty: Adolescents with CED may experience delayed puberty.
- Fractures: Increased risk of bone fractures due to bone fragility.
Diagnostic Tests for Camurati-Engelmann Disease:
The diagnosis of CED is based on a physical examination after an individual presents with limb pain and weakness. Imaging studies such as X-rays show thickening of the long bones which can initially be asymmetric, but progresses to become bilateral and symmetric. The bones involved are usually the femur, tibia, fibula, humerus, radius, ulna, and the skull base. Molecular genetic testing for mutations in TGFB1 is available to confirm the diagnosis.[rx]
- X-rays: Imaging tests that reveal bone abnormalities and thickening.
- Genetic Testing: Identifying mutations in the TGFB1 gene confirms CED.
- Bone Biopsy: A sample of bone tissue may be taken and examined under a microscope.
- Blood Tests: To rule out other conditions and assess overall health.
- Clinical Evaluation: A thorough physical examination by a healthcare provider.
Treatments for Camurati-Engelmann Disease:
Treatment for CED consists of management of symptoms. To manage the pain caused by the thickening of the bones, individuals may be treated with corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs). [rx]Corticosteroids have shown benefits in affected individuals. Although they are helpful to improve walking, the major side effects of taking corticosteroids long term may outweigh the benefits of the drugs. Some of these side effects include high blood sugar, increased risk of infections, and suppressed adrenal hormone production. Losartan has been reported to reduce limb pain and increase muscle strength in some individuals. No formal studies have been completed on the efficacy of losartan and data are limited on the long term effects and benefits of this drug.[rx]
Currently, there is no cure for CED, but treatments aim to manage symptoms and improve the patient’s quality of life.
- Pain Management: Over-the-counter pain relievers or prescription medications can help with pain.
- Physical Therapy: Exercises and stretches to maintain muscle strength and mobility.
- Assistive Devices: Mobility aids like canes or braces may be recommended.
- Surgery: In severe cases, surgery may be necessary to alleviate bone pressure on nerves.
- Medications: Some drugs can help reduce bone pain and inflammation.
- Regular Monitoring: Routine check-ups to track bone changes and manage symptoms.
- Lifestyle Modifications: Healthy diet, regular exercise, and avoiding smoking can contribute to overall well-being.
Medications for Camurati-Engelmann Disease:
- Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): To reduce pain and inflammation.
- Bisphosphonates: To slow down bone remodeling and thickening.
- Corticosteroids: In some cases, these may be prescribed to reduce inflammation.
- Pain Medications: Stronger pain relief medications may be needed for severe pain.
- Disease-Modifying Antirheumatic Drugs (DMARDs): These drugs can help manage the symptoms and inflammation.
Conclusion:
Camurati-Engelmann Disease is a rare genetic disorder that primarily affects the bones. While there is no cure, treatments are available to manage symptoms and improve the quality of life for those with CED. Early diagnosis and medical care are crucial for effective management. If you suspect you or someone you know may have CED, consult a healthcare provider for proper evaluation and guidance.