Harlequin Ichthyosis | Action Medical Research | Children's Charity | Children's Charity

Harlequin ichthyosis: tackling a severe skin disease

First published on 16 June 2010

Updated on 6 May 2014

What did the project achieve?

“We aim to help families affected by an extremely severe, rare skin disease called harlequin ichthyosis or HI,” says Professor David Kelsell of Queen Mary University, London.

Babies with this inherited disease are born with very hard, thick skin, which is formed into diamond-shaped plates, separated by deep cracks. Sadly, they are at high risk of developing life-threatening complications, including serious infections, severe breathing difficulties and dehydration.

“Our funding from Action Medical Research enabled us to improve genetic testing for HI,” explains Professor Kelsell. “Most people don’t realise they are carrying the gene for HI until they have a baby with the condition. Better tests mean parents – and other family members – can feel more informed when planning future pregnancies.”

“We’ve also been studying the disease processes involved in HI and testing several different drugs in the laboratory to see if we can find a way to restore some aspects of normal function to the skin,” continues Professor Kelsell.

“In the past, babies with HI would often die within days of birth,” says Professor Kelsell. “Even now, many babies still lose their lives. We are hoping that, one day, our work will lead to the first ever treatment for babies with this devastating disease.”

This research was completed on 22 August 2012

Babies with harlequin ichthyosis, an extremely severe, rare skin disease, are born with very hard, thick skin, formed into diamond-shaped plates separated by deep cracks. The babies are at high risk of developing life-threatening complications, such as serious infections and breathing problems. Sadly, many lose their lives within just weeks of birth.

Researchers are hoping to develop robust genetic tests for the disease. They are also performing studies that could help identify potential new treatments.



What's the problem and who does it affect?

Abnormal skin puts babies at risk

Babies with harlequin ichthyosis are born with very hard, thick skin, which is formed into diamond-shaped plates, separated by deep cracks. The babies’ facial features are deformed by their abnormal skin and their movement is restricted.

Sadly, babies with harlequin ichthyosis are at risk of developing life-threatening complications. The cracks in their skin make them extremely vulnerable to serious infections. Thick skin on their chest can make it difficult for them to breathe properly, putting them at risk of respiratory failure. They are also prone to feeding problems, dehydration and dangerous fluctuations in their temperature.

Years ago, most babies with harlequin ichthyosis died within a few days or weeks of birth. Even now, despite improvements in care, babies who receive intensive medical support are still thought to have only around a fifty five percent chance of surviving those early weeks.1

Babies who do survive eventually shed the thick, hard plates and develop scaly, red skin, which is constantly itchy. They remain vulnerable to infections, other complications are common and they continue to need specialist care. Further improvements in treatment are urgently needed.

What is the project trying to achieve?

Improving genetic tests and investigating possible treatments

The project falls into two parts. Firstly, the researchers are trying to boost our understanding of the genetics of harlequin ichthyosis to help develop better genetic tests for the disease.

They have already discovered that most babies with the disease have mutations, or changes, in a gene called ABCA12. Genetic tests are available, which can detect these mutations.

The tests don’t work for everyone though, because some of the mutations that cause the disease have not been identified yet. The researchers are investigating what these unidentified mutations are like, so they can develop better genetic tests, which work for more people.

In the second part of the project, the researchers are investigating how harlequin ichthyosis alters the biological processes that take place within the skin, focusing in particular on certain proteins called hormone receptors. This will help them to assess the potential benefits of several possible drugs, which act on those receptors. These studies are taking place in the laboratory, using a model of diseased human skin and samples taken from young adults with harlequin ichthyosis.

What are the researchers' credentials?

Project LeaderProfessor D P Kelsell PhD
Project team
  • Professor Edel A O’Toole MB PhD FRCP FRCPI
LocationCentre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London
Duration2 years
Grant awarded16 March 2010
Start date3 May 2010
End date22 August 2012
Grant amount£105,541.00
Grant codeSP4473, GN1770

We do not provide medical advice. If you would like more information about a condition or would like to talk to someone about your health, contact NHS Choices or speak to your GP. Please see our useful links page for some links to health information, organisations we are working with and other useful organisations. We hope you will find these useful. We are not responsible for the content of any of these sites.

The researchers – Professors David Kelsell and Edel O’Toole – have collaborated for a number of years on the molecular mechanisms that underlie inherited skin diseases. Their work has led to a number of key findings, including the discovery of the gene for harlequin ichthyosis. They have the cooperation of more clinicians managing people with harlequin ichthyosis than any other research group in the world.

The research is taking place in the Centre for Cutaneous Research, within the Blizard Institute for Cell and Molecular Science at Barts and the London School of Medicine and Dentistry. In 2008, Barts and the London was placed alongside Oxford, Cambridge, Imperial College and University College London in the top five research-active medical schools in England offering international levels of excellence in research and teaching.

The researchers’ laboratories are housed within the Institute for Cell and Molecular Science, a unique, award-winning, research building that contains state-of-the-art equipment.

Who stands to benefit from this research and how?

Tests and treatments

The researchers are helping to develop better genetic tests for harlequin ichthyosis, which are more robust and work for more people.

Genetic testing is normally offered to families who are known to be at risk of having a child with harlequin ichthyosis, that is, is couples who have already had a baby with the disease.

Genetic tests can be used during pregnancy to diagnose harlequin ichthyosis before birth. They can also be used later in life to identify carriers of the disease.

Carriers are normally healthy themselves, but if two carriers have a baby together, there is a one in four chance their baby will have the disease and a one in two chance the baby will be a carrier.

The researchers also hope to improve our understanding of the molecular processes that lead to the skin problems seen in harlequin ichthyosis and identify possible new treatments. They believe the lessons learned could prove relevant to the treatment of more common diseases, such as eczema and psoriasis, which both cause skin problems in large numbers of people.


  1. Kelsell DP and O’Toole EA. Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London. Unpublished data.
Help us spread the word