Jeune syndrome: why are some babies born with this rare and disabling condition?

Research Training Fellowship: Dr Miriam Schmidts

Jeune syndrome: why are some babies born with this rare and disabling condition?

Each year, Action Medical Research awards these prestigious grants to help the brightest and best doctors and scientists develop their career in medical research. Dr Schmidt’s grant of £176,583 will fund her two-year study into what causes a rare illness called Jeune syndrome, to improve diagnosis and work towards new treatments.

Introduction

An estimated 600 people in the UK have a genetic condition called Jeune syndrome.^1,2,3 Babies with Jeune syndrome are born with short arms and legs, and an unusually small ribcage, which can cause life-threatening breathing problems.

Researchers have already identified some genetic changes that can cause Jeune syndrome, but estimates suggest only a minority of sufferers carry these changes.⁴ Talented Dr Miriam Schmidts is determined to help people with the condition by searching for more genetic changes that cause it. She hopes to improve diagnosis, boost access to genetic counselling and work towards new treatments.

Dr Miriam Schmidts: “It is wonderful to have this opportunity to make a difference for babies with Jeune syndrome and their families. Despite its severity, the condition does not seem to get a lot of attention – neither in public nor in research. I am very excited that Action Medical Research has given me the chance to change this.”

What's the problem and who does it affect?

Jeune syndrome

An estimated 600 people in the UK and some 69,000 worldwide have a rare, incurable genetic condition, called Jeune syndrome (also called asphyxiating thoracic dystrophy or ATD).^1,2,3

Babies with Jeune syndrome are born with short arms and legs, and an unusually narrow ribcage, which can restrict the development of their lungs, sometimes proving fatal.

“Babies with Jeune syndrome often have severe problems breathing and may require mechanical ventilation, sometimes for many weeks or even months,” explains Dr Schmidts. “Sadly, some babies’ lungs are just too small and they lose their lives. Those who survive often require complicated surgery to enlarge their ribcage. Despite this, many children complain about ongoing difficulties with breathing and some suffer repeated respiratory infections, which can mean they have to be admitted to hospital frequently.”

Children with Jeune syndrome can have other problems too, with their liver, kidneys, or eyesight, for example. Some have polydactyly, which means they have more than five fingers or toes.

Jeune syndrome is inherited, but in many cases, the diagnosis comes as a shock as parents are often unaware that they are carrying a gene for the condition.

What is the project trying to achieve?

Genes for Jeune syndrome

Dr Schmidts is investigating what causes Jeune syndrome.

“Some genetic changes have already been linked to Jeune syndrome,” explains Dr Schmidts. “However, only a minority of people with Jeune syndrome have these changes.⁴ The others do not know why they have been affected.² Genetic testing, whether before or during pregnancy, is therefore not available for most affected families.”

Dr Schmidts is looking for more genetic changes that cause Jeune syndrome. She is sequencing the DNA of around ten children with the disorder, along with the DNA of their parents and siblings as a comparison. The families are donating blood samples for use in the research.

Dr Schmidts is also investigating the underlying disease processes involved in Jeune syndrome, at the molecular level, using a laboratory model. She is focusing on the most recently discovered gene for the disorder. Dr Schmidts is investigating the role of this new gene in detail, focusing on any affect it may have on cilia – hair-like structures, which stick out like antenna from the surface of most cells in the body. Evidence suggests people with Jeune syndrome have dysfunctional cilia, and that cilia play an important part in skeletal development.

What are the researcher's credentials?

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Dr Schmidts is a talented young doctor, who graduated from medical school in Germany in the top seven per cent of students nationwide. She is committed to improving the lives of children with Jeune syndrome: “Having gained four years’ experience caring for sick children during my speciality training in Germany, I know how difficult long-term illness can be during childhood – for the entire family – and how frustrating it is for parents if their child suffers from an illness that is poorly understood. Jeune syndrome is poorly understood, which severely limits treatment options. By boosting understanding, this project could really help families with the disorder.”

Dr Schmidts is working under the expert guidance of three leading researchers at the Institute of Child Health in London, which aims to enhance understanding, diagnosis, therapy and prevention of childhood disease. “The laboratory where I am working, and the Institute of Child Health in which it is located, provide an outstanding research environment, offering state-of-the art equipment and knowledgeable people with lots of expertise,” says Dr Schmidts.

Who stands to benefit from this research and how?

Tackling Jeune syndrome

Dr Schmidts aims to help families affected by Jeune syndrome. An estimated 600 people have the condition in the UK.^1,2 These are the survivors – evidence suggests nearly half of all babies born alive with Jeune Syndrome do not survive, with many dying before their first birthday because of respiratory failure.³

“This Action Medical Research fellowship is an exciting opportunity,” says Dr Schmidts. “It gives me the chance to find more of the genes that cause Jeune syndrome and to improve understanding of what’s going wrong in the body, at the molecular level, which could open the door to the development of new treatments.”

Finding new genes which are involved in Jeune syndrome would give more people access to genetic testing. Testing before or during pregnancy provides information about a couples’ chances of having a baby with the disorder. Testing also gives other family members the option of finding out whether or not they carry the disease gene.

As Dr Scmidts explains: “It can help parents enormously just to know why their baby has been born with an inherited illness like Jeune syndrome, to know which gene is responsible for their baby’s illness and why this leads to health problems.”

References

1. Oberklaid F et al. Asphyxiating thoracic dysplasia. Clinical, radiological, and pathological information on 10 patients. Arch Dis Child 1977; 52:758-65.
2. Orphanet. Jeune syndrome. http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=28... Website accessed May 2011.
3. Kim M et al. Clinical Insights Gained from Eight New Cases and Review of Reported Cases with Jeune Syndrome (Asphyxiating Thoracic Dystropy). Am J Med Genet A 2011; 155(5): 1021-32.
4. Beales et al. IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nature Genetics 2007: 39(6): 727-9.