Current research projects
Measuring elastic in heart and blood vessels using new ultrasound technique
Dr Anatoli Kiotsekoglou, a cardiac research fellow from Thessaloniki, Greece, is working with Dr Child on a PhD research project to study 300 adults and children, using a new harmless technique called Tissue Doppler Ultrasound. This technique measures the elastic recoil of the heart and blood vessels, which is reduced in Marfan syndrome. This novel project should provide early warning signs that preventive medication is required, rather than having to wait for later signs of heart and valve failure, and enlarging aorta. The project will last for 3 years.
Arrhythmia in Children and Adults
The aim of this project is to study the types and frequency of extra or missing heart beats, which can cause sudden death in Marfan syndrome.
A recent study of Marfan syndrome patients using ambulatory electrocardiograms has shown a higher prevalence of arrhythmias than in the normal population, with premature ventricular and atrial contractions, QT segment lengthening and ST depression found more often than in controls. Arrhythmia is not an infrequent cause of sudden death. Occasionally patients have primary conduction delay or aberrant pathways. Both atrial and ventricular dysrhythmia are often associated with mitral valve prolapse causing regurgitation.
Cardiomyopathy, out of proportion to valvular problems, appears occasionally, and some have speculated that there is a primary defect in cardiac muscle.
A cardiologist will analyse 24 hour tape recordings from 100 mutation – proven Marfan syndrome patients, aged 18-75, who attend our tertiary referral clinics. Type and frequency of arrhythmia will be compared with those found in 100 age and sex matched control ECG’s already available and medication will be taken into account. The project will run for 2 years.
Medication in Marfan Syndrome – Pilot Study
The anti hypertension medication Losartan has been shown to prolong life in the Marfan syndrome mouse model, but we are not sure how it works. A pilot study for 1 year in human Marfan syndrome and control volunteers will have to answer this question. This will be followed by a full scale multicentre UK national randomised blind trial of Losartan in Marfan syndrome patients, lasting for 5 years.
Preimplantation Genetic Diagnosis (PGD) now available in the UK
For those couples who wish to be referred for consideration of the pros and cons of preimplantation genetic diagnosis to assure a pregnancy which is not affected with Marfan syndrome, a private London hospital has now been granted a license to offer this service.
Interested couples should initially contact Dr Child as genetic counselling and gene mutation identification are the first steps in the process.
Preimplanation Genetic Diagnosis may become available through the NHS in the future. A contribution to private PGD costs can sometimes be made available from the patients' local Primary Care Trust.
Summer Medical Student Project 2008
This year's project involves the eye in Marfan syndrome which will involve using molecular genetic techniques, and other scientific techniques if necessary, to study the eyes. The main ocular problem is dislocated lenses. This affects 40% of patients with Marfan syndrome, and is a major cause of visual disability, requiring surgery to remove the lens and replace it with an anterior segment lens with fixed focal distance. This is not without risk, including infection in the eye, and detached retina as a result of the removal of the lens and its surrounding fluid.
Since only 45% of patients with dislocated lenses have mutations in the Marfan gene for fibrillin-1, we are curious as to what other causes can be discovered.
This project has been designed to look at the constituents of the ciliary zonular filaments which hold the lens in place. Genes controlling the production of ciliary zonules will then be screened for errors. Medical student Miss Dana Ahnood is pursing this project which is funded by the Marfan Trust.