Role of Cytogenetics and Molecular Cytogenetics in the Diagnosis of Genetic Imbalances

Five decades ago, Tijo and Levan (1956) first recognized the correct chromosome number in man to be 46. Shortly thereafter, several chromosome aneuploid syndromes were identified. In the early 1970s, various chromosomal-banding techniques were developed that allowed the recognition of individual chromosomes and deletions and duplications as etiologies for numerous chromosome syndromes. Slightly more than 10 years ago, fluorescence in situ hybridization (FISH) procedures, using fluorescent-labeled DNA sequences were developed and clinical use of this technique allowed for the identification of cryptic chromosome abnormalities associated with microdeletions and microduplications. The use of subtelomere region–specific FISH probes further led to the identification of deletions and other unbalanced rearrangements in individuals with mental retardation with an apparently normal karyotype. More recently, microarray comparative genomic hybridization was developed, and the technique has recently become incorporated into the clinical cytogenetics laboratory for the identification of submicrosopic deletions and duplications that are associated with developmental delay. The intent of this article is to review the cytogenetic and molecular cytogenetic techniques currently available for the diagnosis of individuals with neurologic disease and genetic imbalances that result in neurologic disturbances and to summarize the most efficient and appropriate use of these techniques in clinical practice.