Motor Impairments in Down Syndrome

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Down Syndrome is a life-long condition found in approximately 800 live births a year [6]. Those with this condition have distinctive physical signs such as a flat and broad nose; a large tongue (or a small mouth); short and stocky stature; oval, upward-slanting eyes; fine straight hair; a short and broad neck; and short broad hands with stubby fingers [6, 2]. Often people with Down syndrome have moderate to severe mental impairments that usually affect their verbal and language-related skills [6, 2]. IQ scores of this population usually fall around 50 [4]. Many also have heart problems [6]. Typically, h
Image 2: Signs of Down Syndrome
owever, these problems will not prevent them from learning acceptable social behavior, manual skills, and activities of daily living [2].

Down Syndrome occurs when one develops with 47 chromosomes instead of the typical 46 [6]. The extra chromosome involves chromosome 21, which ends up being a triplicate instead of a normal pair. Interestingly, this chromosome is the same chromosome that is the topic of study for Alzheimer’s disease [2]. In addition, the brain tissue of one with Down syndrome appears to deteriorate similar to the brain tissue of one with Alzheimer’s disease. Studies show that these traits are the reason that many people with Down syndrome develop Alzheimer’s disease in middle age. Sadly, many with this syndrome die around 40 years of age [6].

Those with Down syndrome also tend to have hyperflexibility and hypermobility of joints, and low muscle tone [4, 7]. In addition, as already briefly mentioned, language development is delayed, visuospatial skills are deficient, and face recognition is weak. Fine motor skills have a lower performance in those with Down syndrome compared to typically developing children [7]. Other common problems in childhood include attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder. It is believed that such disorders occur due to the reduction of the density of the neurons in the brain, which is why the brain appears to deteriorate. The main cells that are reduced in number compared to a typical working brain include interneurons and pyramidal neurons within the cerebral cortex. The brain stem and cerebellum likewise are disproportionately smaller than a normal brain. The delays that often are seen in those with Down syndrome are a result of a reduced synaptic density and a delay in myelination [4]. Those with Down syndrome often also have congenital hypothyroidism which leaves a lack of thyroid hormones to aid in the development of the central nervous system, especially in the activation of sympathetic nervous system and the process of myelination of the nerves. A lack of myelination will increase the time it takes an action potential to conduct a proper response [7].

Most of the disorders already mentioned play into the effect of movement disorders in those with this syndrome. The disproportionately smaller cerebellum affects motor learning and coordination, especially in children and adolescents. Later in life, such motor difficulties can arise due to Alzheimer’s disease. Apraxia is a syndrome of Alzheimer’s that occurs later in the development of the disease, and since those with Down syndrome are more apt to develop Alzheimer’s at a young age, they are more apt to reach the level of the disease that comes with motor disorders at a younger age [8].

Functional Anatomy:

The cerebellum is located on the backside of the brainstem and makes synaptic connections to the brainstem through the peduncles—superior, middle, and inferior. More than a half of the neurons within the central nervous system are located within this structure, allowing for integration and processing of information coming to the brain. The information that comes into the cerebellum is processed in the cerebellar cortex, which will then send that processed information back out for the body to respond accordingly. One way it does this is by sending input to the vestibular nuclei. This connection is what gives the cerebellum the ability to play a role in balance. Other information that comes into the cerebellum includes somatosensory, auditory, and visual. The cerebellum then has connections to the cortex and the spinal cord to control movements related to the information it processes. Although the cerebellum itself does not have direct input to the motor neurons, the connections it makes ultimately lead to the coordination of movement. The vermis of the cerebellum lies in the center portions and is responsible for the proximal limb and trunk coordination, and the lateral hemispheres aid in motor planning and learning of the extremities. When information is processed and ready to leave the cerebellum, the deep cerebellar nuclei act as the primary output pathways. These nuclei include the fastigial nuclei, interpose nuclei, and dentate nuclei, and each send output to different areas of the body. Although the cerebellum does involve some cognitive function, its main function is motor planning. As a result, disorders of the cerebellum include hypotonia, the lack of ability to produce smooth movement, and incoordination [5]. Children with a cerebellum that is not developing correctly or at the proper speed may experience these disorders, as is often seen during the early childhood stages of Down syndrome.

Input into the cerebellum occurs through either the mossy fibers or the climbing fibers. The mossy fibers mostly carry sensory information related to vestibular input, dorsal spinocerebellar input, and cuneocerebellar input. This information is carried to the granule cells of the cerebellum for processing the information and then passing the information to the purkinje cells [5]. In studies done on mice with Down syndrome, the GABAA receptor channels are responsible for adjusting that incoming information. When this adjustment is weak, there may be atypical transferring of information to and from the cerebellum [12].

A typical working brain is rather large and has millions of synaptic connections. The brain, a commonly known structure, is the main organ of the central nervous system. It sits in the top of the head and is protected by the skull. The motor cortices of the brain are associated with the efferent pathways, therefore sending information to the body on various different motor actions for the initiation of movement. These pathways are also known as the pyramidal pathways [5]. If these pathways are damaged there will be movement disorders. Such is the case when the brain starts to deteriorate in those with Down syndrome.
The brain also noticeably shrinks in patients with Alzheimer’s disease. Without a disorder present, the sensory-perceptual system of the brain processes auditory, tactile, and visual information and adjusts the motor responses according to the information it receives. The conceptual system of the brain stores information on both internal and external representations of movements. The production system within the brain then chooses from the stored information to execute an appropriate action given the incoming information the brain is receiving. Errors within the conceptual system, as in the case of Alzheimer’s, result in deficits of being able to perform specific movements [11].

Apraxia occurs as a result of the atrophy of the brain and the decreased activity in the parietal regions. Apraxia is a result of corticobasal degeneration which results in movement disorders due to a lack of limb function [14]. Typically the parietal regions are where multimodal association begins to take place. The visual association neurons within the parietal lobe are responsible for spatial orientation and depth perception, and the vestibular is responsible for balance and eye control. The parietal regions then use this information to assist in motor pathways [5]. Dysfunction in this system, then, reduces preparation for movements and therefore results in motor disorders.

Input and Output Pathways:

The cerebellum has several different functional regions. The vermis region is associated with proximal limb and trunk coordination, as well as aiding in balance. The intermediate hemispheres influence the lateral cortical spinal tract and the rubrospinal tract which innervate the flexors of primarily the upper extremities. As a result, the intermediate hemispheres provide distal limb coordination. The lateral hemispheres of the cerebellum are involved in motor planning and learning of the extremities. Each of these structures aid in movement and coordination through activating the deep cerebellar nuclei. The vestibular input into the flocculonodular region of the cerebellum is processed and then sent to the vestibular nuclei and the reticular formation. The intermediate areas excite the interposed nuclei of the deep cerebellar nuclei which will then cause excitation in the red nucleus and therefore the rubrospinal tract. The lateral hemisphere innervates the dentate nucleus of the deep cerebellar nuclei which then projects to the contralateral red nucleus and the ventrolateral thalamic nucleus [5, 1].
Image 3: Cerebellar Output Pathways
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Image 5: Pathways and Functions of the Cerebellum

In addition to the cerebellum having different functional regions, it is also divided into layers. Mossy fibers begin in the spinal cord and synapse with granule cells in the granule cell layer—the intermost layer. These granule cells then carry the information from the mossy fibers to the molecular layer, the outer layer, where they will bifurcate and become parallel fibers. The job of these parallel fibers is to excite the purkinje cells, which then inhibit the deep cerebellar nuclei. This inhibition aids in coordinating motor activity and regulates the timing component of movements [1]. Overall, the mossy fiber input informs the cerebellum of the desired movement of the cortex as well as providing information on the current state of the body itself. The action of the mossy fibers synapsing to the purkinje cells acts as a feedforward control [1].

In a similar manner, climbing fibers also influence purkinje cells. These climbing fibers begin in the inferior olive which fires when there is disruption in movement. The synaptic connections between the climbing fibers and the purkinje cells changes the strength of the parallel fiber inputs to the purkinje cell. This allows for the cerebellum to be aware of movement that is influencing the cortex [5]. This feedback system informs the cerebellum of what the incorrect movement was, allowing for modification of the movement the next time it needs to occur [1].
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Image 6: The Connective Pathways of the Cerebellum

Pyramidal pathways are descending motor pathways that include the corticospinal and corticobulbar tracts. The corticobulbar syst
pyramidal tracts.jpg
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em controls brainstem nuclei which lead to innervation of cranial muscles. The corticospinal tract controls the motor neurons and interneurons in the spinal cord that drive voluntary and reflexive movements. The lateral corticospinal pathway controls the proximal and distal muscles of the arms and legs and runs laterally in the spinal cord. The anterior corticospinal tract runs medially through the spinal cord and controls posture and balance of the axial and proximal muscles. These pathways are called pyramidal pathways because after they leave the motor cortex and pass through the cerebral peduncle they enter the medulla and form the medullary pyramids. At this point the tract decussates and forms the anterior and lateral tracts. Both tracts then proceed through the anterior or lateral funiculus respectively and down the spinal cord until they reach the alpha motor neurons or interneurons of the anterior and ventral horn [1].

As previously mention
Image 8: Pathways of Visual Processing
ed the parietal regions are where the multimodal association begins to take place. The visual association neurons enter this parietal region through the dorsal stream. When visual input reaches the eye and enters the brain through the optic nerve, it is organized into the “what” and “where” pathways. The where pathway is also known as the M pathway and it projects to the magnocellular layers of the lateral geniculate nucleus (LGN). From there it projects to Brodmann’s area 17, also known as the primary visual cortex (V1), synapsing on layer 4c alpha and 4B. This information proceeds to the visual association cortex (V2), Brodmann’s area 18, and then to the higher level visual association cortex or the dorsolateral parietal-temporal cortex, which is our area of interest. This information is then used to assist in spatial orientation and depth perception [5].

Down Syndrome and Underdevelopment of the Cerebellum:

As already noted, those with Down syndrome often have an underdeveloped forebrain and cerebellum. Studies show that adults with this condition have significant decreases in the cerebellum, the cingulate gyrus, the left medial frontal lobe, the temporal gyrus and the hippocampus, as well as decreases in the white matter of the brainstem. The reduced volume of the cerebellum is cause for many disorders including fine-motor skills, quality of gait, and higher cognitive functions. These higher cognitive functions include cognitive planning, linguistic syntactic processing and overall intelligence. A study on the relationship between brain and cognitive processes in Down syndrome found that the cerebellar abnormalities were majorly involved in the motor dysfunction and hypotonia those with Down syndrome display, therefore the cerebellum is a main area of focus for this particular syndrome [9].
Image 9: Hypotonia

The hypotonia is also a result of the mitochondrial dysfunction found in many with Down syndrome. When the mitochondria is not functioning properly, adenosine triphosphate (ATP) does not properly generate therefore creating problems in the cellular energy within muscles. For this reason, many with this syndrome tend to engage in more passive activities and overall do not exercise as much as those with other intellectual disorders. The recovery time following exercise is lower in those with Down syndrome because of this mitochondrial malfunction [10].

In addition to this, those with Down syndrome tend to have a decreased number of excitatory synapses as well as an increase in inhibitory synaptic markers in the cortex and hippocampus [3]. These impairments cause cognitive disorders as well as movement disorders due the lack of excitatory synapses reaching interneurons to allow for proper formation and function of a properly functioning and fully developed brain. The imbalance of the excitation and inhibition is one reason those with Down syndrome have cognitive deficits [3].

Down Syndrome and Alzheimer’s Disease:

Image 11: CT scans of patients with no disorder, Down syndrome, and Alzheimer's

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Those with Down syndrome have a high occurrence of Alzheimer’s disease due to the extra chromosome 21. Chromosome 21 has a gene called the amyloid precursor protein (APP) that can lead to the formation of Beta-amyloid, a cause for early-onset Alzheimer’s disease [6, 13]. Since those with Down syndrome have an extra chromosome 21, they have a higher chance of developing Alzheimer’s disease. The buildup of this amyloid protein within a cell will cause the cell to die. The cells that are most affected in Alzheimer's are the cells in the hippocampus and association areas of the neocortex [6, 13]. As the neurons and amyloid proteins die, a waxy protein deposit develops and creates what we know as plaque. When protein filaments begin to accumulate in cells, they will become tangled, thereby creating what is known as neurofibrillary tangles. These tangles together with the buildup of amyloid plaque cause cognitive defects [6, 2]. Neurofibrillary tangling can also cause an excess of beta amyloid accumulation [2].
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Image 12: Proteins Responsible for Alzheimer's Disease

Common symptoms of Alzheimer’s begin with a gradual withdrawal from actively engaging in events once common within their lifestyle. Those affected often develop narrower interests, less mental alertness and a lower tolerance for change. As symptoms develop, impaired memory, impaired judgment, confusion, and messiness results [2]. Following these symptoms, more extreme symptoms such as apraxia occur [8].
Apraxia is the impairment of executing learned skilled movements [8]. Deficits that result from apraxia of Alzheimer’s disease include gesture recognition, action error detection, knowledge of action sequencing and the naming of objects. Many of these deficits cause motor errors [11]. Studies show that many with Alzheimer’s have limb apraxia meaning that learned skilled movements of limbs becomes difficult and uncoordinated [11].


Besides the commonly known intellectual impairments that result from Down syndrome, those with Down syndrome also have motor difficulties. These motor difficulties can result from either the lack of development of the brain, specifically the cerebellum, or the increased chances of developing early-onset Alzheimer’s disease leading to apraxia of movement. Despite these issues, those with Down syndrome are able to lead a functional, quality life and tend to be very happy and loving people.


Activities of daily living–Routine activities people perform daily without assistance. Such activities include eating, dressing, bathing, toileting and walking.
Alzheimer's Disease–A type of dementia that involves problems with memory, problem solving and often motor errors.
Apraxia (motor)–A motor disorder caused by damage to the brain. Those with this disorder often have trouble planning or executing learned movements.
Atrophy–Degeneration of cells that causes a decrease in size of an organ
Chromosome 21–A chromosome that, when present as a trisomy instead of a double, causes Down syndrome. The smallest human chromosome.
Down syndrome–A genetic disorder that results from the trisomy of chromosome 21
Hypotonia–Low muscle tone
Mitochondria–Organelles that are involved in generating metabolic energy in cells
Myelination–Layers of membranous material surrounding the axons of nerves in order to decrease conduction time
Purkinje cells–The main output source from the cerebellar cortex. These cells have inhibitory connections onto the cerebellar nuclei
Pyramidal pathways–Descending motor pathways that cross the medulla and form medullary pyramids

Relevant links:

A reading on the cerebellum:
This textbook chapter overviews the anatomy, function, histology, disorders and control systems of the cerebellum. It delves deeper than this paper into how the cerebellum functions.

Helpful videos:
1) Occupational Therapy for those with Down Syndrome
Occupational Therapy Demonstration of Down syndrome. The benefit of occupational therapy for those with Down syndrome is promotion of sensory, cognitive, and motor activities. The goal is help such children develop motor skills, language skills and social skills for higher functioning. Various activities to improve motor activities, endurance, and strength are shown.
2) Physical and Motor characteristics of Down Syndrome.
Looks at various life stages from a clinical perspective and describes the milestones that occur in infant motor skills. Talks about common disorders that come with Down syndrome, including low muscle tone.
3) How Down Syndrome occurs (genetic abnormality)
Explains how the chromosome pairs work and what goes wrong in Down syndrome. Also addresses the different variations of Down syndrome there are and what those differences are on the chromosomal level.
4) Down Syndrome and Alzheimer’s Disease
Explains how Down Syndrome and Alzheimer’s Disease are related, as well as understanding how Down syndrome may be treated to decrease Alzheimer’s. Those with Down syndrome are most likely they get Alzheimer’s because they have an extra chromosome 21 which means they have a greater chance of developing the protein responsible for Alzheimer’s.
5) Alzheimer’s Disease
Explains how Alzheimer’s occurs in the brain, including how the plaques and neurofibrillary tangles occur, therefore killing the neurons and creating a disorder in the brain.

Quiz questions:

Multiple choice/True-False:
1) A physical sign of Down syndrome is:
a. Short broad hands
b. Stubby fingers
c. Fine straight hair
d. All of the above

2) T/F: Typically people have 46 chromosomes

3) T/F: Myelination increases the time it takes an action potential to propagate

4) Disorders of the cerebellum include:
a. Hypotonia, inability to produce smooth movement, incoordination
b. Inability to stop moving, overcorrection, eye twitches
c. Decreased energy levels, dizziness, prosopagnosia

5) T/F: The cerebellum has direct input to the motor neurons

6) Which of the following is a pyramidal pathway:
a. Neopsinalthalamic tract
b. Cerespinal tract
c. Corticospinal tract
d. Basobasilar tract

7) The gene responsible for Alzheimer’s is:
a. ATP
b. ABC
c. PPA
d. APP
e. None of the above

8) T/F: Apraxia is one of the first signs of Alzheimer’s

1) Explain how Alzheimer’s disease develops and why those with Down syndrome have greater chances of developing Alzheimer’s
2) Explain some disorders that could be present as a result of a smaller cerebellum
3) Describe why a decrease in activity of the parietal regions in the brain can cause incoordination of motor skills

Answers to quiz questions:

Multiple choice/True-False:
1) d
2) T
3) F
4) a
5) F
6) c
7) d
8) F

1. (See section of this paper titled "Down Syndrome and Alzheimer's Disease")
2. (See sections of this paper titled "Functional Anatomy" and "Down Syndrome and Underdevelopment of the Cerebellum")
3. (See last paragraph of the section titled "Input and Output Pathways")


[1] Byrne, J.H., Knierim, J., & Concha, J.D. (1997-Present). Neuroscience Online: an electronic textbook for the neurosciences. Retrieved from

[2] Carson, R.C., Butcher, J.N., & Mineka, S. (1998). Abnormal Psychology and Modern Life. Boston, MA: Addison-Wesley Educational Publishers Inc.

[3] Chakrabarti, L., Best, T. K., Cramer, N. P., Carney, R. S. E., Isaac, J. T. R., Galdzicki, Z., & Haydar, T. F. (2010). Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nature Neuroscience, 13(8), 927+. Retrieved from

[4] Charney, D.S. & Nestler, E.J. (2004). Neurobiology of Mental Illness. New York, NY: Oxford University Press, Inc.

[5] Clark, S. Neurophysiological Basis of Movement [Class notes].

[6] Davison, G.C., Neale, J.M., & Kring, A.M. (2004). Abnormal Psychology. Hoboken, NJ: John Wiley & Sons, Inc.

[7] Ferreira-Vasques, A.T., & Lamonica, D.A.C. (2015). Motor, linguistic, personal and social aspects of children with Down syndrome. Journal of Applied Oral Science, 23(4), 424–430.

[8] Green RC, Goldstein FC, Mirra SS, Alazraki NP, Baxt JL, & Bakay RA. Slowly progressive apraxia in Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry 59(3): 312-315, 1995.

[9] Menghini, D., Costanzo, F., & Vicari, S. (2011). Relationship Between Brain and Cognitive Processes in Down Syndrome. Behavior Genetics, 41(3), 381-393. doi:10.1007/s10519-011-9448-3

[10] Phillips, A. C., Sleigh, A., McAllister, C. J., Brage, S., Carpenter, T. A., Kemp, G. J., & Holland, A. J. (2013). Defective Mitochondrial Function In Vivo in Skeletal Muscle in Adults with Down’s Syndrome: A 31P-MRS Study. Plos ONE, 8(12), 1-5. doi:10.1371/journal.pone.0084031

[11] Stamenova, V., Roy, E. A., & Black, S. E. (2014). A model-based approach to limb apraxia in Alzheimer's disease. Journal Of Neuropsychology, 8(2), 246-268. doi:10.1111/jnp.12023

[12] Szemes, M., Davies, R. L., Garden, C. P., & Usowicz, M. M. (2013). Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down's syndrome. Molecular Brain, 6(1), 1-23. doi:10.1186/1756-6606-6-33

[13] Walton, J. (1993). Brain’s Diseases of the Nervous System. New York, NY: Oxford University Press.

[14] Zadikoff C, Lang AE. Apraxia in movement disorders. Brain 128: 1480-1497, 2005.

Image links:

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Image 3: Clark, S. Neurophysiological Basis of Movement [PowerPoint slides]. Retrieved from course Blackboard site.
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Image 5: Clark, S. Neurophysiological Basis of Movement [PowerPoint slides]. Retrieved from course Blackboard site.
Image 6: Clark, S. Neurophysiological Basis of Movement [PowerPoint slides]. Retrieved from course Blackboard site.
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