By: Sumedha Kumar M.Sc. Zoology

By:
Sumedha Kumar
M.Sc. Zoology
WHAT IS TOURETTE’S SYNDROME
 Complex neurodevelopmental disorder characterized
by repetitive, sudden, rapid, nonrhythmic and
involuntary movements or vocalizations, called tics.
Motor tics Vocal tics
Any involuntary, rapid, sudden Any involuntary, rapid, sudden
movement (usually of muscles). vocalizations. They are any tics
Eye blinking that involve the larynx, tongue,
Nose wrinkling throat, sinuses, or mouth.
Jaw thrusting Sniffing
Shoulder shrugging Barking
Wrist snapping Grunting
Neck jerking Throat clearing
Limb jerking Coughing
Hand gestures Chirping
Facial contortions Screaming
Jumping
Touching
WHAT CAUSES THE PROBLEM?
 Dysfunction in thalamus, basal ganglia & frontal
cortex, involving abnormal activity of
neurotransmitters
 Often associated with other problems such as ADHD,
OCD, autism spectrum disorders.
 Tics are involuntary, they will eventually be released.
 The effort spent in suppressing tics is stressful, and
when the tics are eventually released, they will be
more explosive.

HERITABILITY
 Previous family and twin studies have shown that
the majority of cases of TS are inherited.
 TS is highly heritable and has a complex
polygenic background. However, environmental
factors also play a role in the manifestation of
symptoms.
 Shows incomplete penetrance and variable
expression.
 More common in males than females.
 Sporadic cases may arisetourettism
GENETICS OF TS
 Several chromosomal regions were reported as
potential candidate loci for TS
 Abnormalities of the neurotransmitters and their
signal transmissions could lead to the dysfunction
of CSTC neural network and subsequent clinical
manifestation of TS
DOPAMINE RECEPTOR
GENES
 Dopamine D2 receptor (DRD2) gene located on
chromosome 11.
 The TaqIA polymorphism causes an amino acid
change in ANKK1 (Glu713Lys) which changes
substrate binding specificity.
 The normal protein product of the ANKK1 gene acts
as a negative regulator of the TF NFkB.
 DRD2 is regulated by NFkB. This ANKK1 variant can
indirectly affect DRD2 receptor density.
 Increased DRD2 receptor density seen in frontal cortex
and striatum
 Dopamine D4 receptor gene (DRD4) located on
chromosome 11: highly polymorphic.
 Relevance of exon 3 VNTR in DRD4 in TS.
 Significant transmission disequilibrium 7 repeat alleles.
The results suggest that the 7 repeat may predispose to
TS (Liu et al., 2014).
OTHER GENES IMPLICATED IN TS
SLITRK1 Frameshift
Chr 13 mutation and a
mutation in the 3’
UTR
production of
nonfunctional
protein.
HDC – Mutation resulted
Chr 15 from G to A
transition in the
ninth exon of the
gene
formation of
premature
termination codon.
IMMP2L – 5’ end intragenic
Chr 7 deletion
EPIGENETICS
 Perinatal anoxia, hypoxic or ischaemic events
 Prenatal maternal stress, heavy smoking or alcohol
use, early brain injury or lower birth weight
 Psychosocial stress: Dopaminergic neurotransmission
seem to be mediators between stress & tic.
 Autoimmune mechanisms
 a nucleotide variant (var321) in the 3′ UTR of the
SLITRK1 gene leading to its stronger repression by
miR189.
 miR429, involved in midbrain and hindbrain
differentiation and synaptic transmission was
significantly underexpressed in TS patients.
 Increased methylation in dopamine pathway genes
suppresses functional gene products.
 DRD2 hypermethylation leads to dopaminergic
dysfunction.
Methylation of the DRD2

gene: Patients with TS
compared to healthy controls
CONCLUSION
 Tourette Syndrome: An interplay of both genetic and
epigenetic factors
 Targetted and personalised therapeutic approaches
required.
 Disentangling the complex etiology of TS will lead to
the identification of novel targets for drug treatment
and psychotherapy
 A combination of genetic counselling, psychotherapy,
pharmacotherapy can be applied to manage the
disorder.
ACKNOWLEDGEMENT
 I am grateful to our mentor Dr. Dalia Mukhopadhyay
and Dr Deep Chandan Chakraborty for their guidance
and support.
 I am also thankful to Dr Sajal Bhattacharya, Head of
the Dept, Zoology, Asutosh College and Prof. Apurba
Roy, VicePrincipal, Asutosh College.
 I am also grateful to my batch mates for their
valuable suggestions.
REFERENCES
 Progress in genetic studies of Tourette’s syndrome Yanjie
Qi, Yi Zheng, Zhanjiang Li and Lan Xiong, 2017
 Gilles de la Tourette syndrome is associated with
hypermethylation of the dopamine D2 receptor gene
Kirsten R. MüllerVahl , Gesa Loeber, Alexandra Kotsiari,
Linda MüllerEngling, Helge Frieling : 2016
 Functional evaluations of Genes Disrupted in Patients
with Tourette’s Disorder Nawei Sun , Jay A. Tischfield ,
Robert A. King and Gary A. Heiman : 2016
 Genetic Susceptibility and Neurotransmitters in Tourette
Syndrome Peristera Paschou,Thomas V. Fernandez,Frank
Sharp,Gary A. Heiman,and Pieter J. Hoekstra : 2015

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