Dysmorphology and Development: The Patient has the Key
Throughout history people have been fascinated by human malformations. Many cultures have ascribed particularly significance to certain malformations and others have developed beliefs about their causation. In the 19th and 20th century doctors espoused theories about malformations which were based more on superstition and prejudice than on science. Even now many patients attending genetic clinics have developed hypotheses about underlying causes derived from popular beliefs. Diagnostic tests and knowledge about underlying mechanisms have been limited until the last decade and precise counselling for many families has been difficult.
Clinical observations and establishment of a precise diagnosis remains at the heart of human genetic service and research. Studies of human birth defects have allowed identification of developmental genes and revealed mechanisms not suspected from animal studies. New diagnostic tests aid counselling. The findings in a single patient may lead to elucidation of important developmental pathways. Development is not just development of the physical anatomy, but also development of the functioning human; cognitive and behavioural studies are part of genetic research.
The approach, from clinic to laboratory and back to clinic, will be illustrated by our multidisciplinary research on balanced translocations, developmental eye disorders and Williams Syndrome (WS). Cohorts of patients and generation of hypotheses for research have been derived from our clinics. Balanced translocation studies supplemented by large collections of patients with specific anomalies have facilitated identification of genes involved in anterior segment development. Systematic studies of cohorts of WS patients, those with isolated supravalvular aortic stenosis and those with cutis laxa have contributed to the identification of critical regions within the deleted segment of chromosome 7q11.23 and establishment of genotype-phenotype relationships.