Aetiology of mental retardation in Malta using clinical, cytogenetic, arrayCGH and molecular diagnostic techniques

Abstract

Introduction: Genetic aetiology of mental retardation is complex and includes chromosomal abnormalities, monogenic or polygenic conditions, microdeletion syndromes and epigenetic disorders. Methods: A total of 380 individuals were studied using a diagnostic protocol based on dysmorphology and clinical assessment. Investigation included a routine karyotype, testing for cryptic chromosomal rearrangements using FISH and array CGH and DNA testing for the FMR1, MECP2 and other genes as indicated. Results: A specific cause for the mental handicap was identified in 243 individuals (64%). These included a chromosomal abnormality in 86 (22%), fragile X syndrome in 7 (1.8%), Rett syndrome in 9 girls (2.4%), microdeletion syndrome in 4 (1%), recognizable syndromes in 43 (11%), neurological disorders in 25 (6.6%), metabolic conditions in 3 (0.8%), an environmental cause in 26 (6.8%) and autism spectrum disorder in 21 (5.5%). Subtelomeric screening in 73 families identified a microdeletion of 1pter and a t(7p:9p). Array CGH in 15 individuals with normal subtelomeric screens identified a 2MB duplication of 11q25 and a 6MB deletion of 22q12. Conclusion: while clinical diagnosis and conventional techniques form the mainstay of investigation of individuals with mental retardation, molecular cytogenetics and array CGH proved important diagnostic tools increasing the diagnostic yield by 2%.