Camptodactyly-arthropathy-coxa vara-pericarditis syndrome

Overview

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare, inherited disorder characterized by a combination of joint, skeletal, and cardiac abnormalities. The syndrome typically presents in early childhood and includes four major features: camptodactyly (permanent flexion of fingers), non-inflammatory joint disease (arthropathy), hip deformity known as coxa vara, and recurrent or chronic pericarditis (inflammation of the pericardial sac surrounding the heart). Despite these serious features, the condition does not involve systemic inflammation and is distinct from autoimmune forms of arthritis.

Causes

CACP syndrome is caused by mutations in the PRG4 gene, which encodes a protein called lubricin. Lubricin is essential for joint lubrication and the normal function of tendons and other connective tissues. Mutations in this gene result in the absence or dysfunction of lubricin, leading to joint abnormalities and friction-related damage. The condition is inherited in an autosomal recessive pattern, meaning both copies of the gene must be mutated for the individual to exhibit symptoms. Parents of affected children are typically asymptomatic carriers.

Symptoms

The symptoms of CACP syndrome usually begin in early childhood and progress over time. The key clinical features include:

• Camptodactyly: Permanent flexion contracture of the fingers, usually the fifth fingers, present at birth or appearing within the first few years of life

• Non-inflammatory arthropathy: Large joint swelling (especially knees, elbows, and wrists) without signs of inflammation such as redness or heat; joint fluid may be present but lacks inflammatory markers

• Coxa vara: Hip deformity resulting from an abnormally reduced angle between the femoral head and shaft, leading to hip pain and gait abnormalities

• Pericarditis: Recurrent or chronic inflammation of the pericardium, often without systemic signs of infection or inflammation; may cause chest pain, fatigue, or heart murmur in severe cases

• Joint stiffness and reduced mobility

• Growth delays in severe cases

Diagnosis

Diagnosing CACP syndrome involves a combination of clinical assessment, imaging studies, and genetic testing. Diagnostic steps include:

• Clinical examination: Identifying camptodactyly, joint swelling without inflammation, and restricted joint motion

• Radiographic imaging: X-rays or MRI showing characteristic features such as joint effusions, coxa vara, and joint surface irregularities without bone erosion

• Echocardiography: To detect pericardial effusion or pericarditis

• Synovial fluid analysis: Showing non-inflammatory properties (low white cell count)

• Genetic testing: Confirmation of mutations in the PRG4 gene

• Family history: Review for consanguinity or similar presentations among siblings

Treatment

There is no cure for CACP syndrome. Treatment is supportive and aims to improve joint function, manage symptoms, and monitor cardiac involvement. Management strategies include:

• Physical and occupational therapy: To maintain joint mobility and improve functional abilities

• Orthopedic intervention: Surgery may be needed for severe camptodactyly or hip deformity (coxa vara)

• Joint aspiration: Occasionally used to relieve joint swelling or discomfort

• Cardiology monitoring: Regular follow-up for pericarditis; pericardiectomy may be needed in recurrent or constrictive cases

• Avoidance of unnecessary immunosuppressive drugs: Since the arthropathy is non-inflammatory, typical treatments for autoimmune arthritis (like steroids or biologics) are ineffective

Prognosis

The prognosis for individuals with CACP syndrome varies depending on the severity of joint and cardiac involvement. The condition is non-lethal, but it can lead to significant physical disability if not managed effectively. With supportive therapy, many patients can maintain functional mobility and avoid major complications. Early diagnosis and tailored rehabilitation are essential to minimize joint contractures and improve quality of life. Cardiac monitoring is crucial, as pericardial complications can impact long-term health if left untreated.