Understanding congenital spinal abnormality | Action Medical Research

Touching Lives - December 2004

Understanding congenital spinal abnormality

An Action Medical Research team, led by Dr Peter Turnpenny, has identified two new disease genes during their studies into spondylocostal dysostosis — an inherited condition that causes disorganised development of the vertebral column, changes in the shape of the ribcage and a shortened trunk. The two-year £98,000 project helped to characterise the condition — fully defining the symptoms caused by one of the faulty genes — and identified a second faulty gene.

Families from around the world have taken part in the research and the team carried out the first ever genetic prenatal diagnosis on an unborn child. Papers on the findings have been published in the US and UK in what has been widely seen as groundbreaking research.

Congenital spinal malformations occur in a large number of syndromes but often the cause and genetic risks for future children are unknown. These research breakthroughs have come by studying families where the genetic recurrence risk is high.

Breathing difficulties

Though not a life-threatening condition in most cases, people affected by this type of spinal malformation can face a range of problems, from relatively minor abnormalities such as short stature to very severe breathing difficulties caused by the much reduced size of the chest cavity.

Dr Turnpenny’s interest in the condition started in the late 1980s, when he began to study one family with a strongly inherited form of spinal deformity. That interest grew into a full-blown study of spinal problems, but particularly the genes causing spondylocostal dysostosis.

The team, based at the Royal Devon and Exeter Hospital in Exeter, studied samples and X-rays from families around the world. The first gene to be identified is called DLL3 and ^the recent study has uncovered new mutations of that ‘rogue’ gene^. The newly identified gene is called MESP2, and was found by studying DNA from a Lebanese Arab family now living in Australia.

Hundreds of samples

The study has been intense, with samples and X-rays from about 100 families coming under scrutiny by the team. Dr Turnpenny told Touching Lives, “We have seen so many that I can often predict the presence of this rogue gene just by seeing an X-ray of the arrangement of the vertebrae. In this particular condition they form a very distinct pattern. In the case of some X-rays sent to us, we have not proceeded to genetic testing because I can tell straightaway that they are not affected by the mutations in the genes in question.

“^There has been a great deal of interest in the study from both clinicians and geneticists^. The genetic prenatal test we performed was a world first and I think that being able to identify this gene and its mutations will help families affected by spondylocostal dysostosis through better counselling and more accurate diagnosis.”

Real progress

Dr Turnpenny continued, “This kind of genetic research is detailed and time-consuming work. We are immensely grateful to Action Medical Research because without their financial assistance this research simply could not have happened. There is so much still to do and securing funding is a perennial problem, but Action Medical Research certainly made all the difference to us.

“It’s particularly gratifying to be able to present some real progress to the medical and scientific community as a direct result of this grant. ^The Charity’s supporters can see what a difference their donations can make to people’s lives^.

“The number of people suffering from this condition is relatively small, but our research begins to provide an insight into much more common conditions that cause spinal abnormality, helping us to chip away at the mystery that surrounds them and to come up with some answers.”

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