Bruck syndrome

Overview

Bruck syndrome is a rare genetic disorder that falls within the spectrum of osteogenesis imperfecta. It is distinguished by a combination of bone fragility and congenital joint contractures. Individuals with Bruck syndrome typically suffer frequent fractures from minimal trauma, along with joint stiffness and limited mobility due to contractures present at birth. The condition is progressive and can lead to significant physical disability and short stature. Early recognition and intervention play a critical role in managing complications and improving quality of life.

Causes

Bruck syndrome is caused by mutations in genes responsible for bone formation and connective tissue integrity. Two main genetic mutations have been identified in patients with the syndrome:

• FKBP10 mutations – These mutations affect the protein involved in collagen folding and stabilization, leading to decreased bone strength.

• PLOD2 mutations – Alterations in this gene, which is essential for collagen cross-linking, also contribute to the features of bone fragility and joint contractures.

The condition is inherited in an autosomal recessive manner, meaning that a child must receive two copies of the mutated gene (one from each parent) to develop the syndrome. Carriers typically do not show any symptoms.

Symptoms

Individuals with Bruck syndrome exhibit a range of symptoms that primarily affect the skeletal system. Common clinical features include:

• Bone fragility: Frequent, often spontaneous fractures starting in infancy, with bones that are less dense and more prone to breakage.

• Joint contractures: Limited range of motion and stiffness in joints, particularly noticeable at birth and affecting multiple joints such as the elbows, knees, and hips.

• Short stature: Growth impairment is common due to the combined effects of recurrent fractures and skeletal deformities.

• Deformities: Progressive skeletal deformities, such as bowing of the long bones and scoliosis, may occur over time.

• Pain and functional limitations: Chronic pain and reduced mobility can impair daily activities and overall quality of life.

Diagnosis

Diagnosing Bruck syndrome involves a combination of clinical evaluation, radiographic imaging, and genetic testing. The diagnostic process typically includes:

• Medical history and physical examination: A detailed history of fractures, joint contractures, and family history of bone disorders.

• Radiological imaging: X-rays and other imaging studies reveal characteristic bone fragility, deformities, and joint contractures consistent with the syndrome.

• Genetic testing: Molecular analysis identifying mutations in the FKBP10 or PLOD2 genes confirms the diagnosis. Genetic counseling is also recommended for affected families.

• Bone density studies: Dual-energy X-ray absorptiometry (DEXA) scans may be used to assess bone mass and structural integrity.

Treatment

There is no cure for Bruck syndrome; therefore, treatment focuses on managing symptoms, reducing fracture risk, and improving mobility. A multidisciplinary approach is essential. Treatment options include:

• Orthopedic management: Surgical interventions may be necessary to correct deformities, stabilize fractures, or manage joint contractures. Orthotic supports and braces help improve mobility.

• Medical therapy: Bisphosphonates or other bone-strengthening medications may be prescribed to reduce fracture frequency and improve bone density.

• Physical and occupational therapy: Regular therapy is crucial for maintaining joint range of motion, strengthening muscles, and promoting functional mobility.

• Pain management: Chronic pain may be managed through medications, physical therapy, and lifestyle modifications.

• Nutritional support: Adequate intake of calcium and vitamin D is recommended to support bone health.

• Genetic counseling: For families affected by Bruck syndrome, counseling can guide reproductive decisions and inform them about carrier status.

Prognosis

The prognosis for individuals with Bruck syndrome varies based on the severity of bone fragility and joint contractures. Although the condition is progressive and lifelong, early diagnosis and a comprehensive treatment plan can help manage symptoms, reduce the frequency of fractures, and improve functional outcomes. Many patients benefit from ongoing orthopedic care and supportive therapies, which can enhance mobility and quality of life. However, significant physical disability may persist, and complications such as severe scoliosis or chronic pain can affect long-term outcomes. As research advances and new therapeutic strategies emerge, there is hope for improved management and potential interventions in the future.