Chromosomal causes that produce mental retardation: Chromosome disorders that can be diagnosed in the patient

Introduction. In all the aetiological studies carried out on idiopathic mental retardation (MR), chromosomal abnormalities are the factor that makes the most significant contribution. The alterations are more frequent when severe MR is accompanied by a dysmorphic phenotype, but can also be found in subjects with mild MR and with few signs of dysmorphism. Development. This work reports on new genes and critical regions in syndromes with microdeletion, such as Wolf-Hirschhorn, Smith-Magenis and Sotos -which must be taken into account in the genetic diagnosis- and new microduplications like 15q11-q13, which is associated to a behavioural phenotype of autism. The application of new molecular techniques, such as fluorescent in situ hybridisation (FISH) with multiple telomere probes, MLPA (multiplex ligation-dependent probe amplification) and array-CGH (microarray based on compared genomic hybridisation), have shown the important role played by subtelomeric and interstitial rearrangements in the aetiology of MR. Subtelomeric alterations contribute to between 5 and 7% of cases of idiopathic MR, the higher proportion corresponding to deletions, one of the most common of which is deletion 1p36. Studies that evaluate the global genome in idiopathic MR detect from 7% to 20% of cases with anomalies, the interstitial type being more frequent than the subtelomeric kind. Conclusions. The application of new technologies to idiopathic MR opens up a promising new field for the diagnosis of new syndromes with submicroscopic alterations, so that a prognosis can be determined, treatment can be improved and the risk of relapse can be defined. © 2006, Revista de Neurología.