Orthopaedic manifestations of arthrogryposis-renal dysfunction-cholestasis syndrome

J Pediatr Orthop. 2011 Jan-Feb;31(1):107-12. doi: 10.1097/BPO.0b013e3182032c83.

Abstract

Background: Arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome (MIM♯208085) is a rare multisystem disorder, which involves the kidney, liver, skin, and central nervous and musculoskeletal systems. It is inherited as an autosomal-recessive trait, associated with germ-line mutations in the VPS33B gene. In this study, the authors reviewed the orthopaedic manifestations of ARC syndrome.

Materials: Ten patients diagnosed as having ARC syndrome were the subjects of this study. ARC syndrome was confirmed by mutation analysis in 8 of the 10 patients. Medical records and radiographs were retrospectively reviewed with a focus on musculoskeletal manifestations.

Results: Seven patients either expired at 4 to 19 months of age or were presumed to have expired. The remaining 3 patients remained alive at the time of writing this manuscript and were aged from 7 to 23 months. All patients showed musculoskeletal symptoms and/or signs, which included vertical talus (7 feet, 4 patients), pes calcaneovalgus (4 feet, 3 patients), hip dislocation (6 hips, 3 patients), pathologic fractures (5 fractures in 5 patients), and rigid kyphosis (2 patients). No surgical intervention was performed. Orthopaedic treatments, other than fracture management, were abandoned soon after diagnoses were made.

Conclusions: ARC syndrome should be included in the differential diagnosis of arthrogryposis. As there is no specific effective treatment for renal dysfunction and cholestasis, orthopaedic intervention should be postponed until long-term survival is expected, though this is unlikely.

Level of evidence: Level IV, diagnostic studies, case series.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthrogryposis / diagnosis
  • Arthrogryposis / genetics
  • Arthrogryposis / physiopathology
  • Cholestasis / diagnosis
  • Cholestasis / genetics
  • Cholestasis / physiopathology
  • Diagnosis, Differential
  • Female
  • Germ-Line Mutation
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Musculoskeletal Diseases / diagnosis
  • Musculoskeletal Diseases / etiology
  • Musculoskeletal Diseases / physiopathology*
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / genetics
  • Renal Insufficiency / physiopathology
  • Retrospective Studies
  • Vesicular Transport Proteins / genetics*

Substances

  • VPS33B protein, human
  • Vesicular Transport Proteins

Supplementary concepts

  • Arthrogryposis renal dysfunction cholestasis syndrome