Findings, phenotypes, and outcomes in Freeman-Sheldon and Sheldon-Hall syndromes and distal arthrogryposis types 1 and 3: protocol for systematic review and patient-level data meta-analysis

Syst Rev. 2017 Mar 6;6(1):46. doi: 10.1186/s13643-017-0444-4.


Background: Freeman-Sheldon and Sheldon-Hall syndromes (FSS and SHS) and distal arthrogryposis types 1 and 3 (DA1 and DA3) are rare, often confused, congenital syndromes. Few studies exist. With reported diagnosis unreliable, it would be scientifically inappropriate to consider articles describing FSS, SHS, DA1, or DA3, unless diagnoses were independently verified, rendering conventional systematic review and meta-analysis methodology inappropriate and necessitating patient-level data analysis (PROSPERO: CRD42015024740).

Methods/design: As part of a clinical practise guideline development process, we evaluate (1) diagnostic accuracy from 1938-2017, using the Stevenson criteria; (2) the most common physical findings, possible frequency clusters, and complications of physical findings amongst patients with FSS; and (3) treatment types and outcomes. All papers reporting diagnosis of FSS, SHS, DA1, and DA3 are included in searching PubMed and Google Scholar from December 2014 to July 2015 and again before final analyses. Patients with FSS are divided into four phenotype-defined sub-types; all patients are grouped by published diagnosis and medical speciality. Significance of physical findings and historical data is evaluated by chi-square. Associations of physical findings and history with diagnosis and treatment outcome are evaluated by Pearson correlation and linear regression analysis. Two-tailed alpha level of 0.05 is used throughout.

Discussion: The need for detailed patient-level data extraction may limit the types of articles included and questions able to be answered. For treatment and psychosocial health outcomes, we anticipate enhanced difficulties, which may limit significance, power, and results' usability. We hope to outline knowledge gaps and prioritise areas for clinical investigation.

Systematic review registration number: CRD42015024740 Universal Trial Number: U1111-1172-4670.

Keywords: Craniocarpotarsal dystrophy; Data analysis; Distal arthrogryposis type 1; Distal arthrogryposis type 3; Freeman-Sheldon syndrome; Meta-analysis; Review of reported cases; Sheldon-Hall syndrome; Systematic review; Whistling face syndrome.

Publication types

  • Meta-Analysis

MeSH terms

  • Arthrogryposis / diagnosis*
  • Arthrogryposis / physiopathology
  • Craniofacial Dysostosis / diagnosis*
  • Craniofacial Dysostosis / physiopathology
  • Humans
  • Outcome Assessment, Health Care*
  • Phenotype
  • Research Design*
  • Systematic Reviews as Topic

Supplementary concepts

  • Arthrogryposis multiplex congenita, distal type 1
  • Distal arthrogryposis type 2B
  • Freeman-Sheldon syndrome