Risk factors for situs defects and congenital heart disease in primary ciliary dyskinesia

Sunayna Best; Amelia Shoemark; Bruna Rubbo; Mitali P Patel; Mahmoud R Fassad; Mellisa Dixon; Andrew V Rogers; Robert A Hirst; Andrew Rutman; Sarah Ollosson; Claire L Jackson; Patricia Goggin; Simon Thomas; Reuben Pengelly; Thomas Cullup; Eleni Pissaridou; Jane Hayward; Alexandros Onoufriadis; Christopher O'Callaghan; Michael R Loebinger; Robert Wilson; Eddie Mk Chung; Priti Kenia; Victoria L Doughty; Julene S Carvalho; Jane S Lucas; Hannah M Mitchison; Claire Hogg

doi:10.1136/thoraxjnl-2018-212104

Risk factors for situs defects and congenital heart disease in primary ciliary dyskinesia

Thorax. 2019 Feb;74(2):203-205. doi: 10.1136/thoraxjnl-2018-212104. Epub 2018 Aug 30.

Authors

Sunayna Best^{1

2}, Amelia Shoemark^{2

3}, Bruna Rubbo^{4

5

6}, Mitali P Patel¹, Mahmoud R Fassad^{1

7}, Mellisa Dixon², Andrew V Rogers^{2

8}, Robert A Hirst⁹, Andrew Rutman⁹, Sarah Ollosson², Claire L Jackson^{4

5

6}, Patricia Goggin^{4

5

6}, Simon Thomas^{10

11}, Reuben Pengelly¹⁰, Thomas Cullup¹², Eleni Pissaridou¹³, Jane Hayward^{1

12}, Alexandros Onoufriadis¹⁴, Christopher O'Callaghan^{9

15}, Michael R Loebinger⁸, Robert Wilson⁸, Eddie Mk Chung¹³, Priti Kenia¹⁶, Victoria L Doughty¹⁷, Julene S Carvalho^{17

18

19}, Jane S Lucas^{4

5

6}, Hannah M Mitchison¹, Claire Hogg²

Affiliations

¹ Genetics and Genomic Medicine, University College London (UCL) Great Ormond Street Institute of Child Health, London, UK.
² PCD Diagnostic Team, Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Trust, London, UK.
³ School of Medicine, University of Dundee, Dundee, UK.
⁴ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁵ Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
⁶ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ Human Genetics Department, Alexandria University, Alexandria, Egypt.
⁸ Host Defence Unit, Royal Brompton and Harefield NHS Trust, London, UK.
⁹ Department of Infection, Immunity and Inflammation, Centre for PCD Diagnosis and Research, RKCSB, University of Leicester, Leicester, UK.
¹⁰ Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, UK.
¹¹ Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, UK.
¹² North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK.
¹³ Population, Policy and Practice Programme, University College London (UCL) Great Ormond Street Institute of Child Health, London, UK.
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 Department of Respiratory, Critical Care and Anaesthesia, University College London (UCL) Great Ormond Street Institute of Child Health, London, UK.
¹⁶ Department of Respiratory Paediatrics, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
¹⁷ Brompton Centre for Fetal Cardiology, Royal Brompton and Harefield NHS Trust, London, UK.
¹⁸ Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, London, UK.
¹⁹ Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK.

PMID: 30166424
DOI: 10.1136/thoraxjnl-2018-212104

Abstract

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.

Keywords: bronchiectasis; paediatric lung disaese; primary ciliary dyskinesia; rare lung diseases.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Abnormalities, Multiple / epidemiology*
Abnormalities, Multiple / genetics
Ciliary Motility Disorders / epidemiology*
Ciliary Motility Disorders / genetics
Consanguinity
Female
Genetic Predisposition to Disease
Genotype
Heart Defects, Congenital / epidemiology*
Heart Defects, Congenital / genetics
Humans
Male
Mutation
Phenotype
Prevalence
Retrospective Studies
Risk Factors
Situs Inversus / epidemiology*
Situs Inversus / genetics
United Kingdom / epidemiology

Abstract

Publication types

MeSH terms

Grants and funding