Roll of a
dice: Chance- A major cause of mental
disability
It’s a costly and lifelong commitment for
caregivers of a mentally challenged individual; in fact it’s one of the most
costly conditions out there. Consider
the costs of medication, medical care, caregivers, specialized and private
education, special equipment and supplies; at what could be $100 000 a year on one person, it adds up fast. On top of the financial aspect, there’s also
the emotional and physical toll it takes on the family. With
the low availability of spots in long-term care housing programs (example:
group housing run by Community Living), the responsibility of caring for affected
individual often falls solely on the shoulders of the parents.
2% children, meaning 1 in 50, are affected by an
intellectual disabilities; half of whom are born to normal healthy parents. Intellectual disability is characterized by
substantial impairment of the cognitive functions (IQ<70)
which first manifests during childhood. A study by Dutch scientists1
looks at non-syndromic intellectual disability; when individuals have no phenotypic indications of their condition.
Figure 1: Normal distribution of IQ,
most of the population has an IQ between 85-115, gifted individuals 130+, while
those suffering intellectual disabilities <70(http://www.school-psychology.com.au/blog/child-testing-iq-and-intelligence-testing/)
These children look normal, but have impaired
cognitive functions. Only 25% of cases
are diagnosed based on genetics, the other 75% are based off of physical
manifestations. The lack of physical
characteristics in non-syndromic individuals makes diagnosis much harder for
physicians.
There have been many genes, both on the X and
autosomal chromosomes that have been linked to impaired cognitive disorders?
Why are there such a low percentage of cases diagnosed using genetic testing?
Many conditions have locus heterogeneity,
meaning that the disorder can be caused by mutations in genes at different
chromosomal loci. So there is no one loci that codes for the disorder; instead
there are many, and we simply don’t know them all yet. In a recent Dutch study1 exome
sequencing has indicated that 45-55% of non-syndromic cases (after the
exclusion of copy number variants) are associated with de novo point mutations. De novo mutations are not inherited from
parents; instead they are chance mutations that can be caused by mismatched
base pairs, deletions or insertions. The significance is that sporadic intellectual
disability can go undiagnosed for years, even after numerous rounds of genetic
and diagnostic testing; but exome sequencing can be used to identify potential
causal genes.
The results suggest that very few cases are
caused by autosomal recessive gene inheritance (when one copy of the defective
gene is inherited from each parent, resulting in homozygeous recessive
offspring), which prior to this study was believed to be the main cause.
Figure 2: Family with one normal and
one mentally challenged child
Parents who have had a mentally challenged
child are often apprehensive of having a second child due to the fear of having
a second affected child. Aside from the
expense and physical toll of caring for the child, there is often also
guilt. Parents need not feel guilty as
(under normal circumstances) their child’s condition was most likely caused by
a chance mutation that could not of been predicted nor prevented. Normal parents (ie. not affected or carriers
of a known condition such as Down syndrome etc) should not fear having additional
affected child. Their risk for having a
second child who is also cognitively impaired is not elevated, since the
condition is more likely to arise due to de
novo mutations and not from inherited genes.
Food for thought:
With more testing we will be able to create a database of mutations causing intellectual disabilities, which can later be turned into a standardized test.
1Rauch et
al. (2012) Range of fenetic mutations associated with severe non-syndromic
sporadic intellectual disability: an exome sequencing study. The Lancet PMID: 23020937
