mutations are often responsible for intellectual disability, that is, an IQ
level of less than 70
. An IQ test can be done in late childhood at the earliest, but
intellectual disability can be diagnosed before this time based on delay in
milestone achievement by the child. The diagnosis may be established using
Technological advances like array comparative
genomic hybridization (CGH), single-nucleotide-polymorphism (SNP) genotyping
arrays, and massively parallel sequencing have helped greatly in identifying
the genetic defects in conditions that lead to intellectual disability.
When the chromosomes multiply during cell division,
an exact copy of the genes is made in the daughter cell. Sometimes, due to a
problem in the process, some genes may be duplicated or deleted. In many
individuals, these changes in the genes may not cause any problems. In some
cases however, they could lead to intellectual disability.
One of the
most familiar conditions with intellectual disability that is related to a
duplication of a chromosome is Down's syndrome. In Down's syndrome, the
cells have three chromosomes 21 in their cells instead of two. Conditions like
Prader-Willi and Angelman syndromes, the Williams-Beuren syndrome and the
Smith-Magenis syndrome show deletion of particular genes within the
chromosomes. These changes have been detected using chromosome-banding
techniques. Fluorescence in situ hybridization (FISH) techniques can also
detect such changes. Newer techniques like array CGH and SNP genotyping arrays
have helped to identify a number of genetic problems.
People with conditions like schizophrenia, epilepsy
and attention deficit-hyperactivity disorder (ADHD) often have associated
intellectual disability. They have also been found to have genetic
abnormalities. Thus, identifying genetic
abnormalities can help to correlate intellectual disability with conditions
like schizophrenia, epilepsy and ADHD.
In some cases,
changes in a single gene may be responsible for intellectual disability. Among these is the fragile
X syndrome caused by mutation in the gene FMR1and Rett's syndrome. Both these
conditions are associated with a mutation in the X chromosome.
A number of
techniques are used to study gene sequences. Sanger sequencing was the technique used to
produce the first complete human genome sequence. Currently, a technique called
massive parallel sequencing is used
that is quicker and less costly as compared to the initial sequencing
technique. In clinical practice, exome
sequencing is turning out to be more popular. This technique identifies
mutations in the protein-coding parts of the genes and is much more practical
that the previous techniques. However, it cannot detect mutations in the
non-protein coding parts, which may be necessary to identify certain conditions
with intellectual disability.
Analysis of the exomes of the baby as well as the
parents helps to identify de-novo mutations in the baby. This procedure is
called Trio analysis and is used to identify genetic causes of intellectual
disability not related to any syndrome.
The newer gene sequencing techniques are slowly
making their way into diagnostic laboratories where they can identify genetic
diseases more easily, especially those related to intellectual disability.
1 Genomics, Intellectual Disability, and Autism; Heather C Metford et
al; N Engl J Med 2012; 366:733-743