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Bruck syndrome: neonatal presentation and natural course in three patients
J G Leroy1, L Nuytinck, A De Paepe
1Department of Pediatrics Ghent University School of Medicine 185, De Pintelaan, B-9000 Ghent, Belgium.
Insights
Bruck syndrome presents with congenital arthrogryposis and brittle bones, mimicking osteogenesis imperfecta. Its genetic cause remains unknown, despite ruling out collagen gene mutations.
Area of Science:
- Medical Genetics
- Connective Tissue Disorders
- Skeletal Dysplasias
Background:
- Bruck syndrome is a rare genetic disorder characterized by congenital arthrogryposis and recurrent bone fractures.
- Neonatal signs include brittle bones, posing diagnostic challenges due to similarities with osteogenesis imperfecta (OI).
Purpose of the Study:
- To present three unrelated cases of Bruck syndrome, detailing their clinical presentation and diagnostic course.
- To investigate the underlying genetic etiology of Bruck syndrome, given its monogenic nature.
Main Methods:
- Clinical case presentation of three patients diagnosed with Bruck syndrome.
- Radiological assessment and long-term follow-up of disease progression.
- Molecular screening for mutations in COL1A1 and COL1A2 genes, and analysis of collagen I and III.
Main Results:
- Patients exhibited neonatal signs of arthrogryposis and brittle bones, with recurrent fractures and Wormian bones.
- Diagnosis occurred before age two in two patients and in adolescence in one.
- Long-term follow-up showed progressive osteopenia, growth deficiency, contractures, and spinal/pelvic deformities, with normal mental development.
- No alterations in collagen I or III, nor mutations in COL1A1/COL1A2 genes, were detected.
Conclusions:
- Bruck syndrome is a severe connective tissue disorder with an unknown genetic basis.
- The pathogenesis remains elusive, as common collagen gene mutations are excluded.
Abstract:
Three unrelated patients with congenital arthrogryposis and brittle bones, the main neonatal signs of Bruck syndrome, are presented. In infancy and early childhood recurrent fractures of ribs and long bones and persistent Wormian bones in the calvarium are reminiscent of osteogenesis imperfecta (OI) even with white sclerae, normal dental quality and normal hearing as important clinical negatives. The diagnosis was made before two years of age in two, and in adolescence in the third patient. The latter's radiologically documented long-term natural course reveals slow progressivity of osteopenia and growth deficiency, worsening tendon contractures and pterygia in addition to increasing spine and pelvis deformation. Mental development remains normal. Bruck syndrome is monogenic and probably due to homozygosity of an as yet unidentified gene. As no alteration in the collagens I and III is detected and molecular screening reveals no mutation in the COL1A1 and COL1A2 genes, the pathogenesis of this severe disorder of connective tissue remains largely unknown.