What is the management approach for a pediatric or young adult patient with a potential family history of Brocks syndrome?

Bruck Syndrome: Clinical Management Approach

Immediate Diagnostic Confirmation

For any pediatric or young adult patient with suspected Bruck syndrome, particularly with a family history, immediate genetic testing via chromosomal microarray analysis or targeted sequencing of FKBP10 and PLOD2 genes is essential to confirm the diagnosis and guide management. 1, 2

Key Diagnostic Features to Identify

• Skeletal manifestations: Multiple bone fractures (often intrauterine or early infancy), severe osteoporosis, long bone bowing, and progressive scoliosis due to vertebral deformities 1, 2, 3
• Joint contractures: Congenital fixed flexion contractures affecting elbows, wrists, knees, and ankles; bilateral clubfoot deformities; arthrogryposis-like presentation 1, 4, 3
• Chest wall deformities: Pectus carinatum or other thoracic cage abnormalities 4

Critical Cardiac Evaluation

All patients with confirmed or suspected Bruck syndrome must undergo comprehensive cardiac evaluation with echocardiography, as congenital cardiac disease has been documented and can be life-threatening. 2

• Specific cardiac abnormalities reported include tricuspid valve dysplasia with severe regurgitation, mitral valve prolapse with regurgitation, and pulmonary hypertension 2
• The cardiac manifestations likely result from the underlying type I collagen defect affecting cardiac valve structure 2
• Serial echocardiographic monitoring is warranted given the progressive nature of valve dysfunction 2

Comprehensive Multi-System Assessment

Pulmonary Evaluation

• High risk for pulmonary complications: Pulmonary hemorrhage has been documented, likely multifactorial from vessel fragility, rib fractures, and elevated pulmonary pressures 2
• Baseline pulmonary function testing and ongoing respiratory monitoring are essential 2

Prenatal/Perinatal Considerations

• If diagnosed prenatally, monitor for ductus arteriosus complications in the third trimester, as restrictive arterial duct with risk of premature closure has been reported 1
• Delivery planning should involve multidisciplinary team including neonatology and cardiology 1

Therapeutic Management

Bisphosphonate Therapy

Initiate bisphosphonate therapy for bone fragility management and pain control, as this represents the primary evidence-based pharmacologic intervention. 2

• Bisphosphonates assist in reducing fracture frequency and managing bone pain 2
• Dosing should follow protocols established for osteogenesis imperfecta given similar bone fragility patterns 2, 3

Orthopedic Management

• Surgical correction of joint contractures may be considered, though outcomes are limited by underlying bone fragility 4, 3
• Protective measures to prevent fractures during daily activities and positioning 3
• Management of progressive scoliosis with bracing or surgical intervention as indicated 4, 3

Genetic Counseling Requirements

Provide comprehensive genetic counseling emphasizing autosomal recessive inheritance with 25% recurrence risk for future pregnancies when both parents are carriers. 1, 2, 4

• Both FKBP10 and PLOD2 mutations are phenotypically indistinguishable 1
• Prenatal diagnosis is available via chromosomal microarray analysis or targeted gene sequencing 1
• Extended family screening should be offered to identify carriers 4

Critical Pitfalls to Avoid

• Do not dismiss cardiac evaluation: Unlike classic osteogenesis imperfecta, Bruck syndrome can present with severe congenital cardiac disease that significantly impacts prognosis and management 2
• Do not underestimate pulmonary risk: The combination of chest wall deformity, rib fractures, and potential vessel fragility creates substantial risk for pulmonary hemorrhage 2
• Do not delay bisphosphonate initiation: Early treatment may reduce fracture burden and improve quality of life 2
• Do not confuse with isolated osteogenesis imperfecta: The presence of congenital joint contractures (arthrogryposis) is the distinguishing feature that differentiates Bruck syndrome and requires specific genetic testing 4, 3

Prognosis and Long-term Monitoring

• Severity is highly variable, ranging from moderate bone fragility to severe life-threatening phenotypes with cardiopulmonary compromise 2, 4
• Multidisciplinary follow-up involving genetics, orthopedics, cardiology, and pulmonology is mandatory 2
• End-of-life care discussions may be necessary in severe cases with significant cardiopulmonary complications 2