From dysmorphology to genetics

Consider how the advances in molecular medicine in recent years have lead to a great improvement in understanding dysmorphogenesis and the diagnosis of different syndromes of multiple congenital anomalies and mental retardation (ACM/RM). Development of the human brain depends on a very precise sequence of differentiation, proliferation and maturation. Anomalous processes occurring during embryonic development tend to affect the more complex organs. Thus cerebral structure and function are often affected in ACM/RM syndromes. In fact, RM is present in almost half the children with ACM. In recent years different syndromes involving malformations have been described. Their recognition was made possible by the development of imaging techniques, which permit improved morphological analysis of the dysplasic cortex and the availability of new genetic data. Chromosome anomalies are also an important cause of RM and congenital anomalies. Molecular cytogenetic techniques, such as fluorescent hybridization (FISH), currently permit the detection of chromosome rearrangement which is undetectable using standard cytogenetic analysis. For a long time dysmorphology has been based on defining different syndromes using detailed clinical descriptions. These descriptions have certainly been very valuable and important for the diagnosis of many patients and genetic counselling for their families. However, advances in genetics and genomics in recent years have caused great changes in reaching the diagnosis in ACM/RM. The complexity and cost of genetic tests makes it necessary to use them only when there are sufficient clinical grounds, basically when symptoms and signs suggest a specific diagnosis.