Mental Retardation: Study of cytogenetic etiology

Abstract

The present study was carried out in patients of mental retardation for phenotypic and genetic analysis. The medical history of 128 patients suffering from mental retardation was obtained by filling questionnaire, aided with Internet database query for phenotypic characters as guided by clinical assessment and chromosome analysis by Karyotyping. The patients enrolled had following distribution of phenotypic characteristics: Condition Occurrence (%) Developmental delay with convulsions 1.56 Down syndrome 14.06 Mild mental retardation 11.71 Moderate mental retardation 43.75 Severe mental retardation 10.93 Mental retardation (degree unknown) 6.25 Cerebral Palsy 7.81 Autism 3.9 Out of these, 5.46% patients had parents with consanguineous marriages, 69.53% patients had parents with non-consanguineous marriages, while of 25% patients, and the details about consanguinity were not known. Karyotyping was done in 6patients showing Nonsyndromic Mental Retardation by standard technique of GTG Banding. The technique included Trypsinization and Giemsa staining of metaphase chromosomes in Phytohemaglutinin-M-stimulated lymphocytes cultured from peripheral blood. All Karyotypes were normal indicating the absence of any microscopic changes in the chromosome complement of the patients. In addition, phenotypic characterization of patients was also done using POSSUM software. Abnormal features observed in the patients were entered in the POSSUM database, and according to the pre-set algorithm the threshold value was defined for each search. The database query resulted in list of possible syndromes in which combination of these anomalies are observed. Only karyotyping is not sufficient in detecting submicroscopic changes in the chromosomes and hence clue regarding ruling out further anomalies is required. In addition to normal karyotypes, phenotypic characterization in clinical terms can provide a clue to the possible underlying submicroscopic chromosomal anomalies like microdeletions and other rearrangements. These cases are required to be considered for further analysis using whole genome scanning approach for precise conclusions. It is important to reach the diagnosis in non-syndromic patients of mental retardation by clinical assessment and genetic characterization with the available tools for data mining. The combined exercise can help in differential diagnosis, prognosis, selection of specific therapeutic &/or supportive treatment, and risk assessment in future progeny of parents as well as close relatives.