Causes and origins of Tourette syndrome
Encyclopedia
Causes and origins of Tourette syndrome have not been fully elucidated. Tourette syndrome
(also called "Tourette's syndrome", "Tourette's disorder", "Gilles de la Tourette syndrome", "GTS" or "TS") is an inherited
neurological disorder with onset in childhood, characterized by the presence of multiple motor tic
s and at least one phonic tic, which characteristically wax and wane. Tourette's syndrome occurs along a spectrum of tic disorder
s, which includes transient tics and chronic tics.
The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved. Genetic studies have proved that the overwhelming majority of cases of Tourette's are inherited, although the exact mode of inheritance is not yet known, and no gene has been identified. Tics are believed to result from dysfunction in the thalamus
, basal ganglia
, and frontal cortex
of the brain, involving abnormal activity of the brain chemical, or neurotransmitter
, dopamine
. Non-genetic factors—while not causing Tourette's—can influence the severity of the disorder. Some forms of Tourette's may be genetically linked to obsessive-compulsive disorder
(OCD), while the relationship between Tourette's and attention-deficit hyperactivity disorder
(ADHD) is not yet fully understood.
In some cases, tics may not be inherited; these cases are identified as "sporadic" Tourette syndrome (also known as tourettism
) because a genetic link is missing.
A person with Tourette syndrome has about a 50% chance of passing the gene(s) to one of his/her children. Gender
appears to have a role in the expression of the genetic vulnerability, with males more likely to express tics than females. Tourette syndrome is a condition of incomplete penetrance, meaning not everyone who inherits the genetic vulnerability will show symptoms. Tourette's also shows variable expression
—even family members with the same genetic
makeup may show different levels of symptom severity. The gene(s) may express as Tourette syndrome, as a milder tic disorder (transient or chronic tics), or as obsessive compulsive symptoms with no tics at all. Only a minority of the children who inherit the gene(s) will have symptoms severe enough to require medical attention. There is currently no way to predict the symptoms a child may display, even if the gene(s) are inherited.
Recent research suggests that a small number of Tourette syndrome cases may be caused by a defect on chromosome 13
of gene SLITRK1
. Some cases of tourettism
(tics due to reasons other than inherited Tourette's syndrome) can be caused by mutation
. The finding of a chromosomal abnormality appears to apply to a very small minority of cases (1–2%). Studies to locate all of the genes implicated in Tourette's syndrome are ongoing.
The exact mechanism affecting the inherited vulnerability has not been established, and the precise etiology
of Tourette syndrome is not known. Tics are believed to result from dysfunction in the central nervous system
, in the cortical and subcortical regions, the thalamus
, basal ganglia
, and frontal cortex
of the brain. Neuroanatomic
models implicate failures in circuits connecting the brain's cortex
and subcortex, and imaging techniques implicate the basal ganglia
and frontal cortex.
Research presents considerable evidence that abnormal activity of the brain chemical, or neurotransmitter
, dopamine
, is involved. Dopamine excess or supersensitivity of the postsynaptic
dopamine receptor
s may be an underlying mechanism of Tourette syndrome. Other neurotransmitters may also be involved.
, infectious
, or psychosocial
factors—while not causing Tourette's—can influence the severity of the disorder. Twin studies have shown that the twin with lower birth weight is more likely to have more noticeable symptoms. Other perinatal events, such as maternal stress, maternal smoking, and obstetric complications, while not causing tics, may be risk factors for increased severity of tics. Autoimmune processes may affect tic severity in some cases: the unproven and contentious hypothesis that Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, PANDAS, plays a role in the onset of tic disorders and OCD is a current focus of research.
(OCD) may be genetically
linked to Tourette's, or an alternate expression of the condition; genetic studies show an increased rate of tics and obsessive-compulsive behaviors or OCD in relatives of patients with Tourette's, and "reinforce the idea that at least some forms of OCD are etiologically related to TS, and may, therefore, be a variant expression of the same etiologic factors that are important for the expression of tics." Further evidence supporting that OCD and Tourette's are alternative expressions of a common genetic vulnerability is that males inheriting the genetic vulnerability are more likely to display tics, while females are more likely to display obsessive-compulsive traits.
The genetic relationship of attention-deficit hyperactivity disorder
(ADHD) to Tourette's syndrome is less clear, with some evidence to suggest no genetic linkage, and some evidence to suggest that some forms of Tourette's syndrome may be genetically related to ADHD. Not all persons with Tourette's syndrome will have ADHD or OCD, although in specialty clinics where the most impaired patients are treated, a high percentage of patients seeking treatment do have ADHD. The high co-occurrence of ADHD observed in specialty clinics may be due to clinical ascertainment bias. Further study is needed to understand the genetic relationship between ADHD and Tourette's.
Tourette syndrome
Tourette syndrome is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical tics and at least one vocal tic; these tics characteristically wax and wane...
(also called "Tourette's syndrome", "Tourette's disorder", "Gilles de la Tourette syndrome", "GTS" or "TS") is an inherited
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...
neurological disorder with onset in childhood, characterized by the presence of multiple motor tic
Tic
A tic is a sudden, repetitive, nonrhythmic, stereotyped motor movement or vocalization involving discrete muscle groups. Tics can be invisible to the observer, such as abdominal tensing or toe crunching. Common motor and phonic tics are, respectively, eye blinking and throat clearing...
s and at least one phonic tic, which characteristically wax and wane. Tourette's syndrome occurs along a spectrum of tic disorder
Tic disorder
Tic disorders are defined in the Diagnostic and Statistical Manual of Mental Disorders based on type and duration of tics...
s, which includes transient tics and chronic tics.
The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved. Genetic studies have proved that the overwhelming majority of cases of Tourette's are inherited, although the exact mode of inheritance is not yet known, and no gene has been identified. Tics are believed to result from dysfunction in the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, and frontal cortex
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
of the brain, involving abnormal activity of the brain chemical, or neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
. Non-genetic factors—while not causing Tourette's—can influence the severity of the disorder. Some forms of Tourette's may be genetically linked to obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
(OCD), while the relationship between Tourette's and attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
(ADHD) is not yet fully understood.
Genetic factors
Genetic studies, including twin studies, have proven that the overwhelming majority of cases of Tourette syndrome are inherited, although the exact mode of inheritance is not yet known. Tic disorders have long been thought to be inherited as an autosomal dominant gene, but recent research challenges the autosomal dominant hypothesis, and suggests an additive model involving multiple genes. According to Roger Freeman, MD, "Genes that cause tics have not yet been identified; it's very unlikely there's just one. Tics are very familial, but not in a Mendelian pattern (dominant, recessive, etc.). You can't 'inherit' the committee decision to define a problem in a specific way, so TS itself can't be inherited. It's a tic disorder that is inherited."In some cases, tics may not be inherited; these cases are identified as "sporadic" Tourette syndrome (also known as tourettism
Tourettism
Tourettism refers to the presence of Tourette-like symptoms in the absence of Tourette syndrome, as the result of other diseases or conditions, known as "secondary causes"....
) because a genetic link is missing.
A person with Tourette syndrome has about a 50% chance of passing the gene(s) to one of his/her children. Gender
Gender
Gender is a range of characteristics used to distinguish between males and females, particularly in the cases of men and women and the masculine and feminine attributes assigned to them. Depending on the context, the discriminating characteristics vary from sex to social role to gender identity...
appears to have a role in the expression of the genetic vulnerability, with males more likely to express tics than females. Tourette syndrome is a condition of incomplete penetrance, meaning not everyone who inherits the genetic vulnerability will show symptoms. Tourette's also shows variable expression
Expressivity
Expressivity is a term used in genetics to refer to variations in a phenotype among individuals carrying a particular genotype. The term can be used to characterize qualitatively or quantitatively the extent of phenotypic variation given a particular genotype. The term is analogous to the...
—even family members with the same genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
makeup may show different levels of symptom severity. The gene(s) may express as Tourette syndrome, as a milder tic disorder (transient or chronic tics), or as obsessive compulsive symptoms with no tics at all. Only a minority of the children who inherit the gene(s) will have symptoms severe enough to require medical attention. There is currently no way to predict the symptoms a child may display, even if the gene(s) are inherited.
Recent research suggests that a small number of Tourette syndrome cases may be caused by a defect on chromosome 13
Chromosome 13 (human)
Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 114 million base pairs and represents between 3.5 and 4 % of the total DNA in cells....
of gene SLITRK1
SLITRK1
SLITRK1 is a human gene on chromosome 13q31.1. In 2005, medical researchers observed a de novo chromosomal abnormality in a patient with Tourette syndrome which broke the patient's chromosome near SLITRK1...
. Some cases of tourettism
Tourettism
Tourettism refers to the presence of Tourette-like symptoms in the absence of Tourette syndrome, as the result of other diseases or conditions, known as "secondary causes"....
(tics due to reasons other than inherited Tourette's syndrome) can be caused by mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
. The finding of a chromosomal abnormality appears to apply to a very small minority of cases (1–2%). Studies to locate all of the genes implicated in Tourette's syndrome are ongoing.
Pathophysiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of Tourette syndrome is not known. Tics are believed to result from dysfunction in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, in the cortical and subcortical regions, the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, and frontal cortex
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
of the brain. Neuroanatomic
Neuroanatomy
Neuroanatomy is the study of the anatomy and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems, and thus we can begin to speak of...
models implicate failures in circuits connecting the brain's cortex
Cortex (anatomy)
In anatomy and zoology the cortex is the outermost layer of an organ. Organs with well-defined cortical layers include kidneys, adrenal glands, ovaries, the thymus, and portions of the brain, including the cerebral cortex, the most well-known of all cortices.The cerebellar cortex is the thin gray...
and subcortex, and imaging techniques implicate the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
and frontal cortex.
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
Research presents considerable evidence that abnormal activity of the brain chemical, or neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, is involved. Dopamine excess or supersensitivity of the postsynaptic
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...
dopamine receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
s may be an underlying mechanism of Tourette syndrome. Other neurotransmitters may also be involved.
Non-genetic influences
Studies suggest that non-genetic, environmentalNatural environment
The natural environment encompasses all living and non-living things occurring naturally on Earth or some region thereof. It is an environment that encompasses the interaction of all living species....
, infectious
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, or psychosocial
Psychosocial
For a concept to be psychosocial means it relates to one's psychological development in, and interaction with, a social environment. The individual needs not be fully aware of this relationship with his or her environment. It was first commonly used by psychologist Erik Erikson in his stages of...
factors—while not causing Tourette's—can influence the severity of the disorder. Twin studies have shown that the twin with lower birth weight is more likely to have more noticeable symptoms. Other perinatal events, such as maternal stress, maternal smoking, and obstetric complications, while not causing tics, may be risk factors for increased severity of tics. Autoimmune processes may affect tic severity in some cases: the unproven and contentious hypothesis that Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, PANDAS, plays a role in the onset of tic disorders and OCD is a current focus of research.
Relation with OCD and ADHD
Some forms of obsessive-compulsive disorderObsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
(OCD) may be genetically
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
linked to Tourette's, or an alternate expression of the condition; genetic studies show an increased rate of tics and obsessive-compulsive behaviors or OCD in relatives of patients with Tourette's, and "reinforce the idea that at least some forms of OCD are etiologically related to TS, and may, therefore, be a variant expression of the same etiologic factors that are important for the expression of tics." Further evidence supporting that OCD and Tourette's are alternative expressions of a common genetic vulnerability is that males inheriting the genetic vulnerability are more likely to display tics, while females are more likely to display obsessive-compulsive traits.
The genetic relationship of attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
(ADHD) to Tourette's syndrome is less clear, with some evidence to suggest no genetic linkage, and some evidence to suggest that some forms of Tourette's syndrome may be genetically related to ADHD. Not all persons with Tourette's syndrome will have ADHD or OCD, although in specialty clinics where the most impaired patients are treated, a high percentage of patients seeking treatment do have ADHD. The high co-occurrence of ADHD observed in specialty clinics may be due to clinical ascertainment bias. Further study is needed to understand the genetic relationship between ADHD and Tourette's.
External links
- The Genetics of Gilles de la Tourette Syndrome — 53-minute video where David Pauls discusses the results of a genetic linkage study for Tourette syndrome.