• Clubfoot is a common, but little researched, inborn disorder of the lower limb and foot. Its cause is poorly understood but it is known that genetic factors are important. • • Clubfoot, known as congenital talipes equinovarus (CTEV) • Clubfoot – condition where the patient cannot stand on one or both feet with the sole of the foot flat on the ground. The most common form is where the foot is twisted downwards and inwards so that the patient walks on the outer edge of the upper sole of the foot • 1 in 1000 children is born with clubfoot (1:500 in Scotland) • It is twice as common in boys than girls • Still unsure how, but the condition can develop in the first trimester (first three months) of pregnancy – it can be detected pre-natally by ultrasound scan but at present there is no way of treating the feet before birth • It can be simply corrected by orthopaedic splinting and physiotherapy in the early months of infancy – (e.g. weekly leg casts and gentle manipulation of the foot). • But as many as 80% of children with clubfoot may need surgery between 4 – 9 months after birth. Previously Previous SPARKS funding has allowed the researchers to establish the largest study of clubfoot in the world. Understanding the causes and evaluating the results will help treatment or even prevention in the future. March 2000 - Feb 2001 Club feet: Cause and Management £44,958 over 1 year, Aberdeen University Medical School This first study investigated how club foot is passed from parents to children using DNA analysis and computer programmes to digitally analyse photos of the condition. The study contacted 15 scottish clubfoot centres and collated evidence from 116 families through questionnaires and DNA samples. Using computer analysed digital photography, they measured the condition – the technical term for this is anthropometry – where you take measurements of the human body or its parts to determine the difference between normal and abnormal development. • This has lead to a new method of edge detection/assessment of the calf volume in club foot and many other conditions such as damage or wasting to the calf of sport people or other patients. • Found new evidence of seasonal variation in clubfoot – when you are born can be a factor • Lead to a better understanding of the epidemiological factors (environment, where born) in club foot and the genetic basis for club foot. • A unique DNA collection April 2001 – Jan 2004 Finding the genes that cause clubfoot £107,647 over 3 years at Aberdeen University Looked for the genes associated with Clubfoot and studied the interaction of genes and the environment. Involved sufferers in other countries. Researchers gathered lifestyle and medical information and DNA samples from more than 750 children with clubfoot, their parents and families here in the UK (parent support group STEPS), Netherlands (parent support group VOK) and an isolated Pacific Population of Vanuatu (high frequency of clubfoot in population). This resource gave researchers the ability to use several study designs to unravel the genetics and environmental causes of clubfoot. They have found: o that genetic factors may play a part – the variation in the genetic control of metabolism of the B vitamin folate may have a role in the cause of clubfoot. o pregnancy factors may also play a role in the cause of clubfoot – possible mid trimester link o confirmed an association with maternal smoking and identified a potential role of paternal smoking o established collaboration to assess the role of a gene causing mouse clubfoot (gammy) in human clubfoot. o a genome-wide scan for linkage in seven cases from the Pacific population of Vanuatu Currently This current project “Exploring the causes of clubfoot in Europe” continues this work by o extending their work on folate metabolism genes and its possible role; o studying promising candidate genes for clubfoot and; o using specialized techniques in an isolated population(Vanuatu) to identify other clubfoot genes.