J Med Genet 49:21-26 doi:10.1136/jmedgenet-2011-100378
  • Genotype-phenotype correlations
  • Original article

CHRNG genotype–phenotype correlations in the multiple pterygium syndromes

  1. Eamonn R Maher1,2
  1. 1Centre for Rare Diseases and Personalised Medicine and Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
  2. 2West Midlands Regional Genetics Service, Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, UK
  3. 3Centre Hospitalier Universitaire Dijon, Plateau Technique de Biologie, Dijon Cedex, France
  4. 4Labor Krone, Bad Salzuflen, Germany
  5. 5Center for Human Genetics, University of Leuven, Leuven, Belgium
  6. 6North West Thames Regional Genetics Service, The North West London Hospitals NHS Trust, Middlesex, UK
  7. 7Peninsular Regional Genetics Service, Clinical Genetics Department, Royal Devon and Exeter Hospital, Exeter, UK
  8. 8National Centre for Medical Genetics, Our Lady Hospital for Sick Children, Crumlin, Dublin 12, Ireland
  9. 9Service de Genetique, CHU-Hopital Nord, 42055 Saint Etienne Cedex 2, France
  10. 10North East Thames Regional Genetics Service, Clinical Genetics Department, Great Ormond Street Hospital, Great Ormond Street, London, UK
  1. Correspondence to Dr Julie Vogt, Clinical Genetics Unit, Birmingham Women's Hospital, Metchley Park Road, Edgbaston, Birmingham, B15 2TG, UK; julie.vogt{at}
  1. Contributors JV and ERM conceived, designed and coordinated the study. LF, LB, KB, J-PF, SH, LI, EK, SL, RT and LW contributed to patient enrolment in the study and provided patient information and samples. JV, ERM, NM, PR and FM analysed and interpreted the data. JV and ERM drafted the article. All authors have read and approved the final manuscript.

  • Received 31 July 2011
  • Revised 14 October 2011
  • Accepted 28 October 2011


Background Germline mutations in the CHRNG gene that encodes the γ subunit of the embryonal acetylcholine receptor may cause the non-lethal Escobar variant (EVMPS) or the lethal form (LMPS) of multiple pterygium syndrome (MPS). In addition CHRNG mutations and mutations in other components of the embryonal acetylcholine receptor may present with fetal akinesia deformation sequence (FADS) without pterygia.

Methods In order to elucidate further the role of CHRNG mutations in MPS/FADS, this study evaluated the results of CHRNG mutation analysis in 100 families with a clinical diagnosis of MPS/FADS.

Results CHRNG mutations were identified in 11/41 (27%) of families with EVMPS and 5/59 (8%) with LMPS/FADS. Most patients with a detectable CHRNG mutation (21 of 24 (87.5%)) had pterygia but no CHRNG mutations were detected in the presence of central nervous system anomalies.

Discussion The mutation spectrum was similar in EVMPS and LMPS/FADS kindreds and EVMPS and LMPS phenotypes were observed in different families with the same CHRNG mutation. Despite this intrafamilial variability, it is estimated that there is a 95% chance that a subsequent sibling will have the same MPS phenotype (EVMPS or LMPS) as the proband (though concordance is less for more distant relatives). Based on these findings, a molecular genetic diagnostic pathway for the investigation of MPS/FADS is proposed.


  • Competing interests None.

  • Ethics approval Ethics approval was provided by South Birmingham Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.