Genetic evaluation and counseling in head and neck syndromes

Genetic diagnosis and counseling are dynamic areas of clinical medicine that must keep pace with the rapid advances in developmental and molecular biology. Identification of developmental pathways in primitive organisms has often led to the recognition of similar programs for development in vertebrates. An understanding of the function of genes studied in mice through knock-out and targeted mutation studies provides animal models for human dysmorphogenetic syndromes and candidate genes for human syndromes. As soon as a gene is cloned for a human disorder and mutations are identified in affected individuals, clinical applications in diagnosis, prediction, and prevention rapidly develop. Understanding how a gene functions and the consequences of its mutation will aid in counseling and will help determine prognosis. Some mutations that interrupt pathways early in development will cause malformations that are static or nonprogressive, as seen in PAX6 and Shh mutations. Others, such as FGFR mutations, will continue to interfere with normal morphogenesis throughout the period of growth and development in the regions affected by the mutated gene. Clinical geneticists and genetic counselors, by assuming responsibility for identifying individuals with or at risk for genetic disorders, serve as interpreters and guides to the options presented by this new technology.