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Risk factors for situs defects and congenital heart disease in primary ciliary dyskinesia
  1. Sunayna Best1,2,
  2. Amelia Shoemark2,3,
  3. Bruna Rubbo4,5,6,
  4. Mitali P Patel1,
  5. Mahmoud R Fassad1,7,
  6. Mellisa Dixon2,
  7. Andrew V Rogers2,8,
  8. Robert A Hirst9,
  9. Andrew Rutman9,
  10. Sarah Ollosson2,
  11. Claire L Jackson4,5,6,
  12. Patricia Goggin4,5,6,
  13. Simon Thomas10,11,
  14. Reuben Pengelly10,
  15. Thomas Cullup12,
  16. Eleni Pissaridou13,
  17. Jane Hayward1,12,
  18. Alexandros Onoufriadis14,
  19. Christopher O’Callaghan9,15,
  20. Michael R Loebinger8,
  21. Robert Wilson8,
  22. Eddie MK Chung13,
  23. Priti Kenia16,
  24. Victoria L Doughty17,
  25. Julene S Carvalho17,18,19,
  26. Jane S Lucas4,5,6,
  27. Hannah M Mitchison1,
  28. Claire Hogg2
  1. 1 Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health, London, UK
  2. 2 PCD Diagnostic Team, Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Trust, London, UK
  3. 3 School of Medicine, University of Dundee, Dundee, UK
  4. 4 Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  5. 5 Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK
  6. 6 NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
  7. 7 Human Genetics Department, Alexandria University, Alexandria, Egypt
  8. 8 Host Defence Unit, Royal Brompton and Harefield NHS Trust, London, UK
  9. 9 Department of Infection, Immunity and Inflammation, Centre for PCD Diagnosis and Research, RKCSB, University of Leicester, Leicester, UK
  10. 10 Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, UK
  11. 11 Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, UK
  12. 12 North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK
  13. 13 Population, Policy and Practice Programme, University College London (UCL) Great Ormond Street Institute of Child Health, London, UK
  14. 14 Division of Genetics and Molecular Medicine, Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s Hospital, London, UK
  15. 15 Department of Respiratory, Critical Care and Anaesthesia, University College London (UCL) Great Ormond Street Institute of Child Health, London, UK
  16. 16 Department of Respiratory Paediatrics, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK
  17. 17 Brompton Centre for Fetal Cardiology, Royal Brompton and Harefield NHS Trust, London, UK
  18. 18 Fetal Medicine Unit, St George’s University Hospitals NHS Foundation Trust, London, UK
  19. 19 Molecular and Clinical Sciences Research Institute, St George’s, University of London, London, UK
  1. Correspondence to Dr Hannah M Mitchison, Department of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; h.mitchison{at}


Primary ciliary dyskinesia (PCD) is associated with abnormal organ positioning (situs) and congenital heart disease (CHD). This study investigated genotype–phenotype associations in PCD to facilitate risk predictions for cardiac and laterality defects. This retrospective cohort study of 389 UK patients with PCD found 51% had abnormal situs and 25% had CHD and/or laterality defects other than situs inversus totalis. Patients with biallelic mutations in a subset of nine PCD genes had normal situs. Patients with consanguineous parents had higher odds of situs abnormalities than patients with non-consanguineous parents. Patients with abnormal situs had higher odds of CHD and/or laterality defects.

  • bronchiectasis
  • paediatric lung disaese
  • primary ciliary dyskinesia
  • rare lung diseases

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  • HMM and CH are shared senior authorship.

  • Contributors SB compiled, managed and analysed the clinical and genetic data. SB, AS and BR searched clinical records and compiled the clinical data. SB, MPP, MRF, ST, RP, TC, JH and AO performed genetic analyses. AS, MD, AVR, RAH, AR, SO, CLJ and PG performed clinical cilia functional testing and imaging studies. EP advised on and performed statistical analysis. CO’C, MRL, RW, EC, PK, JSC, JSL and CH contributed to clinical analysis and data management. VLD and JSC contributed to cardiac data management and interpretation. SB, AS, JSC, HMM and CH wrote the manuscript. HMM, JSC and CH designed the project and are responsible for the overall content. All authors reviewed the data, revised the manuscript for logical content and approved the final version.

  • Funding This research is supported by the BEAT-PCD: Better Evidence to Advance Therapeutic Options for PCD network (COST Action 1407). Work at the Royal Brompton Hospital was partially supported by the European Society of Cardiology. SB was supported by an Academic Clinical Fellowship funded by the National Institute of Health Research (NIHR) and Imperial College London Biomedical Research Centre (BRC). Work in Southampton is supported by NIHR Respiratory BRC and NIHR Wellcome Trust Clinical Research Facility. Work by AS was independent research funded by a postdoctoral research fellowship from the NIHR and Health Education England. EP, CO’C and HMM are supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. HMM acknowledges grants from Action Medical Research (GN2101), Newlife Foundation (10-11/15) and the Great Ormond Street Hospital Children’s Charity.

  • Disclaimer The views expressed in the submitted article are the authors’ own and not an official position of the institution or funder.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval London Bloomsbury Research Ethics Committee.

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

  • Data sharing statement No additional data.

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