Chromosomal abnormalities account for 35-40% of SMR and 10% of MMR.
Chromosomal aneusomies (loss or excess of chromosomal material) cause a
gene dosage difference for a large number of genes and the phenotypic
effect is pleiotropic; therefore, they always cause syndromes of
multiple congenital anomalies and mental retardation.
The commonest autosomal abnormalities are trisomies, particularly
involving chromosomes 13, 18 and 21 and these are all associated with
increased maternal age. The most common aneusomy in live newborns is
trisomy 21 (Down syndrome), which is invariably associated with mental
retardation. Almost all chromosomal aneuploidies, which involve an
alteration in the amount of chromosome material, are associated with
mental retardation. It is not certain whether this is due to dosage
effects of specific genes within the duplicated or deleted segments, or
to a more general effect of aneuploidy per se. It is certainly true
that individuals with chromosomal aneuploidy share some nonspecific
features in common such as poor growth, microcephaly, epicanthic folds
and unusual palmar creases, in addition to features more specific to
the chromosomes involved.
Some chromosome abnormalities occur in
the mosaic form (where some cells show the normal 46 chromosomes and
others have an extra chromosome) and for disorders, which are usually
seen in the full form, mosaicism will confer a milder phenotype.
However, there are some conditions, which are lethal in the full form
and are therefore found only in the mosaic form in surviving
individuals. The common chromosomal abnormalities associated with
mental retardation are summarized in [Table - 3]