The image above is a common facial tic many children with Tourette Syndrome display. Motor tics are the first symptoms.
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TOURETTE SYNDROMEGilles De La Tourette Syndrome, commonly known as Tourette Syndrome is a neurological disorder that is characterized, and stereotyped, by involuntary, sudden and repetitive movements or vocalizations called tics (1). Motor and vocal tics have been known to arise as two types, simple and complex. Simple motor tics include eye blinking, nose twitching, and head and shoulder jerking. While these all involve a limited number of muscles within the body, complex motor tics are distinct and usually coordinated patterns involving many more muscles. Some complex tics include touching objects, jumping and full body twisting (3). Simple motor tics are the first symptoms that arise in children with Tourette Syndrome. Vocal tics appear later than motor tics but are also a main characteristic of the disorder. Sniffing and throat clearing are common where as more complex vocalizations include repeating others (echolalia) and repeating one's self (palilalia) (1). Coprolalia, or the use of inappropriate language, is a symptom that is more often stereotyped within the media relating to Tourette's. However, only 10-15% of individuals diagnosed with Tourette Syndrome display this type of vocal tic (3). In many patients, co-morbid conditions are common. A co-morbid condition is an associated disorder that is commonly diagnosed along with a primary disorder. Obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) are two that often overlap with individuals already diagnosed with Tourette Syndrome. Sometimes ADHD or OCD are the most complicated part of treatment and diagnosis (2). Reference Figure 1.
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PREVALENCEAlthough there has been some debate Tourette Syndrome is commonly diagnosed in children 2-15 years of age. Tics are a common sign of Tourette's however, specific criteria must be met in order to make a diagnosis, much like other behavioral and neurological disorders (2). This disorder is 3 to 4 times more prevalent in males than females (3) and according to the U.S. National Library of Medicine, Tourette Syndrome is estimated to affect 1 to 10 in 1,000 children. This disorder occurs in all populations, ethnic groups, and social classes world wide (2).
TREATMENTTourette Syndrome is a treatable disorder and varies in severity from mild to severe cases. Many individuals do not require medication (4). With the proper education provided to family members, peers, and children along with supportive counseling to those affected, medication can be avoided. Motor and vocal tics increase in severity due to stress, boredom, fatigue, excitement and excess intake of caffeine. However, when tics interfere with day-to-day functions, effective medications are available (3). In about 2/3 of cases tics have been known to lessen in severity and frequency into the teen years and adulthood (1).
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Hdc – histidine decarboxylase
Researchers at Yale University have recently shown that a mutation within the Hdc gene is associated with the cause of Tourette Syndrome.
Tourette Syndrome is a disorder that is characterized by sensorimotor gating deficiencies and abnormalities of the basal ganglia and related brain circuits. Within the basal ganglia, pictured in Figure 2, molecules work together to create a variety of functions that include voluntary motor control, learning behaviors or "habits" and emotional functions (6). Histamine and dopamine are two important compounds within the body that interact in the basal ganglia circuits (7).
The Hdc gene, or histidine decarboxylase gene, is located on chromosome 15 in the
human genome. At Yale, scientists have demonstrated on mice, and observed in humans,
that a mutation in the Hdc gene (Hdc W317X) causes symptoms of Tourette syndrome through reducing production of the enzyme it encodes (7). Hdc is a dominantly acting gene that encodes histidine decarboxylase. This enzyme is used within the body to convert histidine, an amino acid, to histamine (8). Once converted, histamine influences levels of dopamine, a neurotransmitter. Dopamine plays important roles in the brain, affecting motor control, arousal, cognition and emotion functions. Within the basal ganglia dopamine binds to receptors to trigger, in the case of Tourette Syndrome, motor control. In both mice and humans carrying the Hdc mutation (W317X) dopamine receptor binding was altered in comparison to mice and humans without the mutation (7). These alterations in binding and lowered histamine production caused tic-like motor deficiencies in mice which were consistent with motor tics of humans diagnosed with Tourette Syndrome. Although functional activity links and causal connection between Hdc disruption and neurobiological abnormalities of Tourette's still remains unclear, the recognized Hdc mutation and role of histamine in Tourette Syndrome is the next step in finding new treatments for Tourette patients (9).
Tourette Syndrome is a disorder that is characterized by sensorimotor gating deficiencies and abnormalities of the basal ganglia and related brain circuits. Within the basal ganglia, pictured in Figure 2, molecules work together to create a variety of functions that include voluntary motor control, learning behaviors or "habits" and emotional functions (6). Histamine and dopamine are two important compounds within the body that interact in the basal ganglia circuits (7).
The Hdc gene, or histidine decarboxylase gene, is located on chromosome 15 in the
human genome. At Yale, scientists have demonstrated on mice, and observed in humans,
that a mutation in the Hdc gene (Hdc W317X) causes symptoms of Tourette syndrome through reducing production of the enzyme it encodes (7). Hdc is a dominantly acting gene that encodes histidine decarboxylase. This enzyme is used within the body to convert histidine, an amino acid, to histamine (8). Once converted, histamine influences levels of dopamine, a neurotransmitter. Dopamine plays important roles in the brain, affecting motor control, arousal, cognition and emotion functions. Within the basal ganglia dopamine binds to receptors to trigger, in the case of Tourette Syndrome, motor control. In both mice and humans carrying the Hdc mutation (W317X) dopamine receptor binding was altered in comparison to mice and humans without the mutation (7). These alterations in binding and lowered histamine production caused tic-like motor deficiencies in mice which were consistent with motor tics of humans diagnosed with Tourette Syndrome. Although functional activity links and causal connection between Hdc disruption and neurobiological abnormalities of Tourette's still remains unclear, the recognized Hdc mutation and role of histamine in Tourette Syndrome is the next step in finding new treatments for Tourette patients (9).
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Header Image Credit http://joanlandinosays.com/ten-common-questions-about-tourettes-syndrome/
REFERENCES
1 "Tourette syndrome" Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 2 Feb 2014 http://ghr.nlm.nih.gov/condition/tourette-syndrome
2 "Tourette Syndrome" Madisons Foundation. Retrieved 2 Feb 2014 http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=618
3 "Tourette Syndrome Fact Sheet" National Institute of Neurological Disorders and Stroke: Reducing the burden of neurological disease. Retrieved 2 Feb 2014 http://www.ninds.nih.gov/disorders/tourette/detail_tourette.htm
4 "Tourette syndrome" NIH National Center for Advancing Translational Sciences & ORDR Office of Rare Diseases Research. Retrieved 3 Feb 2014 http://rarediseases.info.nih.gov/gard/7783/resources/resources/8
5 "HDC histidine decarboxylase [homo sapiens (human)]" NCBI: Gene. Retrieved 3 Feb 2014 http://www.ncbi.nlm.nih.gov/gene/3067
6 "Basal ganglia" Wikipedia: The Free Encyclopedia. Retrieved 3 Feb 2014 http://en.wikipedia.org/wiki/Basal_ganglia
7 "Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice" Baldan et al. 2014 Neuron Vol 81 Issue 1, p77-90. Retrieved 3 Feb 2014 http://www.cell.com/neuron/abstract/S0896-6273(13)01004-0
8 "Histamine" Wikipedia: The Free Encyclopedia. Retrieved 3 Feb 2014 http://en.wikipedia.org/wiki/Histamine#Synthesis_and_metabolism
9 "Cause of Tourette Syndrome discovered" Yale Daily News: The oldest college daily. Retrieved 3 Feb http://yaledailynews.com/blog/2014/01/14/cause-of-tourette-syndrome-discovered/
REFERENCES
1 "Tourette syndrome" Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 2 Feb 2014 http://ghr.nlm.nih.gov/condition/tourette-syndrome
2 "Tourette Syndrome" Madisons Foundation. Retrieved 2 Feb 2014 http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=618
3 "Tourette Syndrome Fact Sheet" National Institute of Neurological Disorders and Stroke: Reducing the burden of neurological disease. Retrieved 2 Feb 2014 http://www.ninds.nih.gov/disorders/tourette/detail_tourette.htm
4 "Tourette syndrome" NIH National Center for Advancing Translational Sciences & ORDR Office of Rare Diseases Research. Retrieved 3 Feb 2014 http://rarediseases.info.nih.gov/gard/7783/resources/resources/8
5 "HDC histidine decarboxylase [homo sapiens (human)]" NCBI: Gene. Retrieved 3 Feb 2014 http://www.ncbi.nlm.nih.gov/gene/3067
6 "Basal ganglia" Wikipedia: The Free Encyclopedia. Retrieved 3 Feb 2014 http://en.wikipedia.org/wiki/Basal_ganglia
7 "Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice" Baldan et al. 2014 Neuron Vol 81 Issue 1, p77-90. Retrieved 3 Feb 2014 http://www.cell.com/neuron/abstract/S0896-6273(13)01004-0
8 "Histamine" Wikipedia: The Free Encyclopedia. Retrieved 3 Feb 2014 http://en.wikipedia.org/wiki/Histamine#Synthesis_and_metabolism
9 "Cause of Tourette Syndrome discovered" Yale Daily News: The oldest college daily. Retrieved 3 Feb http://yaledailynews.com/blog/2014/01/14/cause-of-tourette-syndrome-discovered/
University of Wisconsin – Madison
Spring 2014 Genetics 564 |
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