Genetics, epidemiology and outcome measurement of Idiopathic Congenital Talipes Equinovarus
The aetiology, pathogenesis and optimal management of Idiopathic Congenital Talipes Equinovarus (ICTEV) remain the subjects of ongoing debate. The aims of this thesis were to test the hypothesis that both heritable and environmental factors play a role in the aetiology of ICTEV, and to develop a valid technique for severity and outcome assessment of ICTEV. I therefore investigated genetic inheritance through family pedigrees, the role of environmental factors by means of parental questionnaires, and evaluated outcome using both digital images and parental multiple-response questions. Families were recruited from 15 Scottish and 2 English centres generating189 participants. The children had a mean birth weight of 3.5kg, and 94.9% were singleton pregnancies. Breech and forceps deliveries were significantly higher in ICTEV compared with the general population. One in five mothers had been taking the oral contraceptive pill at the time of conception, 2.5% of mothers had experienced a stillbirth, compared to a population rate of 0.61 per 100 live births. Paternal (90%) and maternal (28%) tobacco use at time of conception together generated pre-natal exposure to 93.4% of ICTEV infants. This represents convincing evidence of an aetiological link between parental tobacco exposure and ICTEV, and has not been shown in previous studies. Males were twice as commonly affected as females. Risks to relatives of ICTEV infants have been calculated from pedigrees. Male cases were more likely to have a family history. A seasonal trend with a peak in Spring was observed. Subjective assessment of outcome did not significantly favour any one method. For the first time, a clinically validated digital photographic technique has been described to reliably measure calf muscle volume, demonstrating a 12-15% difference between sides in unilateral cases. Given the evidence for heterogeneity in aetiology (environmental and genetic factors) and in outcome, doubt is cast upon the unified diagnosis of ICTEV.