Monday, October 22, 2012

Medical Monday - The Brain and Down syndrome: Part 2: The Brain and Trisomy 21 (31 for 21, Day 22)

As we explored last week, the brain is a complex organ with highly specialized areas that control almost all of the body's functions (both conscious and unconscious).  This week I hope to shed somelight on the differences between a 'typical' brain and one with Trisomy 21.

Anatomical Differences

Lateral surface of left cerebral hemisphere
of the 'typical' brain
Through autopsy, MRI imaging and related studies, many anatomical differences have been noted in the brain with Trisomy 21. There is:
  • Statistically a brain that is 18% smaller by volume 
  • A smaller than average occipital lobe and brain stem
  • Alterations in the layers of the cortex (cortical lamination)
  • A simplified appearance to the sulci (the furrows or wrinkles in the surface of the brain.  The inside of the furrow is known as a sulcus, while the crest is known as a gyrus)
  • A smaller cerebellum, which could account for the hypotonia, motor-coordination, articulation, fluency, syntactic, language and cognitive issues with Down syndrome.
  • Smaller frontal lobes (although in proportion to the rest of the smaller sized brain) could account for cognitive deficits, executive dysfunction, inattention, tendency towards perseveration.
  • Smaller temporal lobes than the average brain, although larger comparatively when size corrected for the smaller overall size of the brain with Down syndrome.
  • Larger white matter volumes within the temporal lobe which could attribute to cognitive dysfunction
  • Adults with DS have been found to have a larger parahippocampal gyrus (the fold of the cerebral cortex that lies over the hippocampus that is normally composed mainly of grey matter). One study found an inverse relationship between IQ and parahippocampal gyrus size. 
  • Smaller hippocampus volumes have been found in adults with DS which may contribute to memory and language deficits
  • A brain with DS, noting the 'boxy' shape and shortened
    superior temporal gyrus (Image courtesy of
    Virginia Commonwealth University's Department of Pathology)
  •  A comparatively smaller superior temporal gyrus which could significantly contribute to language deficits as it is the location of both the primary auditory cortex (region responsible for sound) and Wernicke's Area (region responsible for speech and language recognition)
  • More grey matter in the parietal lobe.  This could account for the strength of visuospacial processing and visuospacial short term memory.
There is also a general larger volume of grey matter in the subcortical region. There are several theories surrounding this. One, it could suggest a different rate in development for the cortical and subcortical areas. For example, no abnormalities are seen in fetal brains with DS until the third trimester; by then the majority of the basal ganglia are formed. The cerebral cortex, however, continues to grow and develop beyond this time, which suggests that the subcortical regions are mainly unaffected by the onset of the abnormalities. Another theory is that programmed cell death (apoptosis) is not effective, causing a large number of basal ganglia to continue to operate long after they become dysfunctional. Some children with DS also have vascular dysplasias and focal calcification of basal ganglia

Histological Differences

There are also differences in the cells themselves in the Trisomy 21 brain:
  • Neurons have a reduced number of dendrites, less synapses an are often clustered irregularly. Early in development, a infant with DS has a rapidly growing dendritic tree, which connects neurons together. Within the first year however, this growth slows.
  • Oligodendrocytes, a type of glial cell, create the mylen sheaths which insulate the axons of a nerve cell. There is some dysfunction with these cells in Down syndrome which is seen as delayed mylenation in the frontal and temporal lobes
  • There are more microglial cells found in Trisomy 21
  • There can be a presence of nerve cell heterotopias in the white layers of the cerebellum (which could indicate some disturbance of cell migration in the embryo)
  • A decreased amount of granular cells throughout the cerebral cortex
  • A decreased amount of neurons in the occipital cortex and hypothalamus
  • Larger amount of astrocytes in the temporal lobe

Other theories:


It is possible that over expression of the T21 gene affects apoptosis or programmed cell death. This could potentially account for lower numbers of neurons in specific areas of the brain and the prevalence of leukemia in the DS population. Also, compounds known as Reactive Oxidant Species could contribute to neurodegeneration by oxidation.

Other factors to consider:


Beta-amyloid expression in children with Down syndrome is no different than in normal children. However, it disappears after age two then reappears in adulthood.

The accumulation of beta amyloid deposits, senile plaques and neurofibrillary tangles starts at approximately age 40 which may represent or lead to an Alzheimer's like neurodegeneration


[Next week: Down syndrome, Alzheimer's and a Very Special Mouse]




Becker, L., T. Mito, S. Takashima, and K. Onodera. "Growth and Development of the Brain in Down Syndrome." Progress in Clinical and Biological Research, 373 (1991): 133-52. Web.

Lubec, G., and E. Engidawork. "The Brain in Down Syndrome (TRISOMY 21)." The Journal of Neurology 249.10 (2002): 1347-356. Web.

Pinter, Joseph D., Stephan Eliez, J. Eric Schmitt, George T. Capone, and Allan E. Reiss. "Neuroanatomy of Down’s Syndrome: A High-Resolution MRI Study." The American Journal of Psychiatry 158 (2001): 1659-665.


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2 comments :

  1. Jen. I think I remember reading somewhere, in a recent book on creativity, about some area of the brain related to self control, which is smaller in individuals with Down syndrome... I remember thinking aHa, but didn't really follow up. ARe there some things, in your opinion, that have an impact that we should learn to accommodate instead of trying to change (when change would be challenging and make the person feel like they are failing?)

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  2. Hi Nan... chalk it up to the lack of caffeine or perhaps the hour, but I'm having a bit of difficulty following your question. Are you referring to the prefrontal cortex? What kind of things are you thinking of?

    Without totally "getting it", I will say that there will be various things that we can adapt learning for, working on strengths, etc. Change is challenging for everyone, regardless of chromosome count and the size of the various parts of your brain. However, I firmly believe that every child is capable of success; when they are not reaching that, then we need to find out how we can make it so.

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