Primary Ciliary Dyskinesia: Better Diagnosis | Action Medical Research | Children's Charity

Primary ciliary dyskinesia: improving diagnosis could relieve children’s suffering

First published on 29 October 2010

Updated on 7 August 2014

What did the project achieve?

“We aim to improve the lives of children with a rare disorder called primary ciliary dyskinesia or PCD,” says Dr Mitchison of University College London’s Institute of Child Health.

Symptoms of PCD often begin soon after birth, with babies needing oxygen because of breathing difficulties. They can face a lifetime of recurrent chest and ear infections, often developing hearing loss and sometimes permanent lung damage.

“Unfortunately, long delays in diagnosis of this rare condition can result in children suffering unnecessarily severe symptoms,” says Dr Mitchison. “Many have developed advanced lung damage before it has been realised what’s wrong. Our work could help change things for the better.”

Dr Mitchison’s team has discovered that changes in two genes play a key role in causing the majority (73 per cent) of cases of a subtype of PCD that affects 12 per cent of all sufferers.1 They have also identified two new genes for the condition.2

“We are currently developing new, improved genetic tests for PCD. This includes a comprehensive ‘gene panel’ that we have developed in collaboration with the Great Ormond Street Hospital clinical services, which we use to simultaneously screen for mutations in all the known PCD genes,” says Dr Mitchison. “We hope this will mean more children with the condition can be diagnosed sooner, so they can benefit from treatment earlier in their lives. The right treatment can relieve children’s suffering, help stop their illness from getting worse and protect their lungs from permanent damage, improving children’s lives considerably.”

References

1. Antony D et al. Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms. Hum Mutat 2013; 34: 462-72.

2. Onoufriadis A et al. Splice-site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia. Am J Hum Genet 2013; 92: 88-98.

This research was completed on 31 October 2012

Each year in the UK, over 100 children are diagnosed with a debilitating, lifelong illness called primary ciliary dyskinesia (PCD).1,2 The children suffer recurrent ear and chest infections, with some eventually needing a lung transplant, typically during adulthood. Early diagnosis can relieve children’s suffering by giving them access to treatment that eases symptoms and slows disease progression. However, the diagnostic process is complicated, unpleasant and often lengthy. Researchers are hunting for genes for PCD, in the hope of simplifying diagnosis and improving children’s lives.

What's the problem and who does it affect?

Delays in diagnosis cause unnecessary suffering

At least 3,000 people in the UK have a debilitating illness called primary ciliary dyskinesia (PCD).3-5 Symptoms often begin soon after birth, with babies needing oxygen because of difficulties breathing.

Children with the illness face a lifetime of recurrent chest and ear infections, meaning they miss a lot of school. They often need surgery to insert grommets and hearing aids. Some find their lungs become permanently damaged, meaning they eventually need surgery to remove part of their lung or even a lung transplant.

Once their illness is correctly diagnosed, children are offered regular, twice-daily physiotherapy, which helps clear their lungs. Many also take antibiotics on a regular basis to tackle infections. The right treatment can relieve children’s suffering, help stop their illness from getting worse and protect their lungs from permanent damage.

However, PCD sometimes goes undiagnosed, or is mistaken for other illnesses, such as cystic fibrosis or asthma, which cause similar symptoms. Even if PCD is suspected, diagnosis is complicated and unpleasant, with children having to undergo several tests at specialist centres, including biopsies of the lining of their nose.

Difficulties and delays with diagnosis are causing unnecessary suffering. Improvements are needed urgently.

What is the project trying to achieve?

A gene hunt

PCD is an inherited illness. Research has already identified genetic changes – or mutations – that cause PCD in nine different genes.

However, only around 40 per cent of children with PCD have one of these mutations.6 The genetic cause of the other children’s illness remains unknown. The researchers are therefore hunting for more of the genes that cause PCD.

Children with PCD all have abnormal cilia – tiny hair-like projections, which line the airways and ears. Cilia are supposed to beat rapidly, to sweep germs and dust out of the lungs.

In PCD, cilia don’t work properly. Their beating action is sluggish or absent. Mucus and bacteria build up in the airways, making children susceptible to infection and congestion. All of the genes for PCD that have been identified so far cause cilia to be abnormal.

In this project, the researchers are studying the DNA of 24 children with PCD from 11 different families. The children’s parents and siblings are also taking part in the study. The children all have abnormalities in specific components of cilia, called radial spokes. The researchers are hunting for the genetic changes that cause these abnormalities. They are also investigating how any changes they find lead to disease.

What are the researchers' credentials?

Project LeaderDr H M Mitchison PhD
Project team
  • Dr Eddie MK Chung MB ChB MRCPCH MD
LocationMolecular Medicine Unit and General and Adolescent Paediatric Unit, Institute of Child Health, University College London
Other locations
  • General and Adolescent Paediatric Unit, Institute of Child Health, University College London
Duration2 years
Grant awarded29 July 2010
Start date1 November 2010
End date31 October 2012
Grant amount£99,954.00
Grant codeSP4534, GN1773

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The project leader, Dr Hannah Mitchison and her clinical colleague, Dr Eddie Chung, have been investigating the genetic causes of PCD for over a decade. They are leading experts in this area of research and have an excellent track record. They played a vital role in identifying five of the nine genes for PCD that have been published to date. Only four other groups in the world can claim to have similar expertise in the genetics of PCD.

The researchers have forged the UK’s largest resource for genetic studies into PCD – over 150 families have volunteered to participate in their important, ongoing research, with many having donated blood samples for use in that work.

The research is taking place at the Institute of Child Health (ICH) in London, which aims to improve the health and wellbeing of children, and the adults they will become, through world-class research, education and public engagement. The ICH provides an excellent environment for this research into the genetic causes of PCD.

Who stands to benefit from this research and how?

Earlier diagnosis could improve children’s lives

The researchers aim to find more of the genes for PCD, a debilitating illness that typically strikes soon after birth and persists throughout life, causing recurrent chest and ear infections.

The researchers hope their work will eventually help speed up and simplify the diagnosis of PCD. They envisage the development of a ‘PCD chip’, which could enable quick, one-stop, non-invasive screening of children for all the genes that are known to cause PCD. This could spare children from having to visit specialist centres for lots of unpleasant tests, such as biopsies of the lining of their nose.

There is no cure for PCD, but the earlier a child’s illness is diagnosed, the sooner the most appropriate treatment can begin and the better their quality of life. Treatment can relieve children’s suffering, help stop their illness from getting worse and protect their lungs from permanent damage.

Improving diagnosis could help children understand their illness more clearly. It could mean their siblings and other relatives have the option of finding out whether or not they are carriers of the illness. Further down the line, the researchers believe their work could also lead to brand new therapies for PCD.

References

  1. National Commissioning Group Diagnostic Service. 2010. Personal correspondence.
  2. A. Barbato et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J. 2009; 34(6):1264-76.
  3. O’Callaghan C et al. Diagnosing primary ciliary dyskinesia. Thorax 2007; 62(8): 565-7.
  4. O’Callaghan C et al. High prevalence of primary ciliary dyskinesia in a British Asian population. Arch Dis Child 2010; 95:51-2.
  5. Kuehni CE et al. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J 2010; Jun 7 [Epub ahead of print].
  6. Leigh MW et al. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet med 2009; 11(7):473-87.
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