Today’s
post is about another supposedly rare cause of autism called Agenesis of the Corpus Callosum (ACC).
As regular readers of this blog will
have noted, extremely rare causes of autism, taken as a group are not so rare
after all. In fact it seems that autism is just a very large collection of
somewhat rare biological conditions.
Of
the very few "Autism Dads" I have had a face to face conversation
with, one has a child with ACC and another has a son with the even rarer Sotos
syndrome. Sotos syndrome is characterized by gigantism, mild ID/MR and often
autism. Mutations in the NSD1 gene cause Sotos syndrome
ACC is physical malformation of
the brain that shows up clearly on MRI scans and potentially shows up on the
mother’s regular ultrasound scans.
The corpus callosum is a wide, flat bundle of fibers about 10 cm
long that connects the left and right sides
of the brain. It facilitates communication
between the two sides of the brain.
Agenesis of the corpus callosum (ACC) is a birth defect in which there is a complete or partial absence of the corpus callosum.
ACC
leads to behaviors compatible with a diagnosis of autism or Asperger’s in about half of cases.
Symptoms
of ACC vary greatly among individuals,
as they do in all types of autism. Seizures
are common, some people have poor motor coordination, and some people are
non-verbal.
It is suggested
by many that a diagnosis of ACC is not compatible with a diagnosis of autism;
this just shows a lack of understanding.
Autism is just a description of
behaviors, ACC is a biological diagnosis, like Fragile X syndrome or Down
Syndrome. So if a person has autistic
behaviors caused by ACC, it is still autism, it is just autism with an explanation
of its origin.
The
most famous person with ACC was Kim Peek who was the inspiration for the character
played by Dustin Hoffman in the well-known film Rain Man.
In
addition to having the physical ACC malformation it has been suggested that the
cause of ACC in his case was likely FG Syndrome.
Most mutations that cause FG syndrome can be found in the MED12 gene.
However, mutations have also been found in FMR1, FLNA, UPF3B, CASK, MECP2, and
ATRX genes. Mutations on
these different genes lead to the different types of FG syndrome, all with
similar characteristics. Congenital
heart defects are common and Peek died of a heart attack aged 58, outlived by his father.
Agenesis of the
Corpus Callosum and broader Autism
Undoubtedly
there are people diagnosed with autism, who have undiagnosed ACC, since they
never had an MRI scan. Just like there
are many people with autism who have an undiagnosed, but treatable, Chiari “brain hernia”.
It also
appears that having a smaller corpus callosum, but falling short of what would
be diagnosed as ACC by the MRI scan, is a feature of some people’s autism. You
could consider it as partial ACC, like we had partial biotin/biotinidase
deficiency.
A very
recent paper from the 2016 Society for Neuroscience annual meeting suggested one reason
why autism is more prevalent in males.
The study looked at infecting
pregnant rats with group B streptococcus to activate the mothers immune
system. Inflammation was then triggered in
the fetal side of the placenta, but only in male fetuses.
The males go on to
develop brain and behavioral features reminiscent of autism.
Female fetuses were somehow protected and
developed normally. Hopefully Barons
Cohen will read this and stop looking for undiagnosed females with autism. There are many good reasons why autism is less prevalent in females, and they are
not just “better at hiding it”, as the so-called expert claims.
What is
interesting is that in the male pups with “autism” they had an unusually thin corpus callosum. It turns out that such minor malformations occur in broader human autism.
The largest of the white matter tracts is
known as the corpus callosum, which allows communication between the two
hemispheres (halves) of the brain.
"The size of the corpus callosum was smaller in the group with autism, suggesting that inter-regional brain cabling is disrupted in autism," Dr. Just said.
In essence, the extent to which the two key brain areas (prefrontal and parietal) of the autistic participants worked in synchrony was correlated with the size of the corpus callosum. The smaller the corpus callosum, the less likely the two areas were to function in synchrony. In the normal participants, however, the size of the corpus callosum did not appear to be correlated with the ability of the two areas to work in synchrony.
"This finding provides strong evidence that autism is a disorder involving the biological connections and the coordination of processing between brain areas," Dr. Just said.
"The size of the corpus callosum was smaller in the group with autism, suggesting that inter-regional brain cabling is disrupted in autism," Dr. Just said.
In essence, the extent to which the two key brain areas (prefrontal and parietal) of the autistic participants worked in synchrony was correlated with the size of the corpus callosum. The smaller the corpus callosum, the less likely the two areas were to function in synchrony. In the normal participants, however, the size of the corpus callosum did not appear to be correlated with the ability of the two areas to work in synchrony.
"This finding provides strong evidence that autism is a disorder involving the biological connections and the coordination of processing between brain areas," Dr. Just said.
CONCLUSIONS:
These longitudinal results suggest atypical early childhood
development of the corpus callosum microstructure in autism that
transitions into sustained group differences in adolescence and adulthood. This
pattern of results provides longitudinal evidence consistent with a growing
number of published studies and hypotheses regarding abnormal brain connectivity
across the life span in autism.
The study suggests that white matter abnormalities
manifest early in autism, says Thomas Frazier, director of Center for Autism at
the Cleveland Clinic in Ohio. “It also serves as a nice demonstration that
brain abnormalities in autism will become clearest and most helpful for
pointing to etiology when we look at them developmentally, longitudinally,
rather than at a single age," he says.
The findings do not imply that corpus callosum
abnormalities cause autism, cautions Ralph-Axel Müller, professor of
psychology at San Diego State University, who was not involved with the work.
Rather, any irregularities in the corpus callosum may stem from other
abnormalities in the brain that have been associated with autism, Müller says.
Still, changes in the corpus callosum may help to explain
why autism symptoms worsen in some individuals and improve in others, Travers
says. "Is there some aspect of white matter micro-structure occurring
early in the developmental pathology that locks in persistent autism across the
lifespan? What are the mechanisms? Can they be unlocked?” she says. “These will
be important questions for future research.”
Conclusion
It is estimated that at one in 4,000 individuals has a
disorder of the corpus callosum. I suspect it is more, but you would need to
routinely give MRI scans to people diagnosed with autism to find out.
It is clear that milder disorders of the corpus callosum may
be a feature of many people’s autism and those changes over time in the corpus callosum may help to explain why autism
symptoms worsen in some individuals and improve in others.