Acta Padiatrica, 2005; 94: 1608-1 6 14
Taylor & Francis
Taylor 6Fmwis Group
Tourette syndrome and other tic disorders in a total population
of children: Clinical assessment and background
NAJAH KHALIFA’>2 & ANNE-LIIS VON KNORRING’
Department o f Neuroscience, Child and Adolescent Psychiatry, University Hospital, Uppsala, Sweden, and
2Department o f Women’s and Children’s Health, University Hospital, Uppsala, Sweden
Aim: To describe the symptoms, onset, heredity, pre-/pennatal events and socio-economic status in Tourette syndrome (TS)
and other tic disorders. Methods: From a total population of 4479 children, 25 (0.6%) with TS, 58 (1.3%) with chronic motor/
vocal tics (CMVT) and 214 (4.8%) with transient tics (TT) in the last year were found. A three-stage procedure was used:
tic screening, telephone interview and clinical assessment. The TS group was compared with 25 children with TT and
25 controls without tics. Results: The mean age of the first symptoms of TS was significantly lower than the onset of CMVT.
All except one with TS had contact with medical services. The tics of children with TS were significantly more severe than
the tics of others. Younger age of onset of TS indicated more severe tics. Parents and siblings of children with TS had an
increased prevalence of tic disorders, obsessive-compulsive behaviour (OCD), attention-deficithyperactivity disorder
(ADHD) and depression. Eighty per cent had a first-degree relative with a psychiatric disorder. A non-significant increase with
regards to reduced optimality score in the pre-, pen- or neonatal periods was found in children with TS compared to controls.
No differences were found concerning socio-economic status.
Conclusion: Almost all children from a total population with TS have sought help from medical services. An increased
prevalence of tics, OCD, depression or ADHD was found in the parentdsiblings of children with TS, which draws attention to
the importance of thorough investigation of family members.
Key Words: Age o f onset, heredity, perinatal complications, tic severity, Tourette syndrome
The onset of Tourette syndrome (TS) ranges from 2 to
2 1 y, with a mean of 7 y. Symptoms usually begin with
motor tics, and the onset of phonic tics usually comes
later. Initially, vocal tics involve noises rather than
words [ 1-41. Coprolalia (the inappropriate and
involuntary uttering of obscenities) occurs in less than
one-third of clinical populations [ 11. In fact, it has been
suggested that this may be culturally determined, as
only 4% have true coprolalia in Japan  and some
countries show higher figures than in the USA or
Europe . The aetiology of TS remains obscure, but
hereditary factors play an essential part in the patho-
genetic chain of events. Investigations of TS since the
1970s have consistently demonstrated an increased risk
of TS among relatives of patients with TS. Family
studies have found a history of tics in 8-57% of parents.
Comorbidity with obsessive-compulsive disorder
(OCD) and attention-deficitlhyperactivity disorder
(ADHD) are common among patients with TS. If
OCD, ADHD and panic attacks are included, the rate
of familiar transmission is elevated to 1582% [6-141.
Recently, there have been suggestions that a variety of
other factors are also involved in the aetiopathogenesis
of TS, including pre- and perinatal stresses/insults, and
various bacterial and viral infections [ 15,161. Severity
of maternal stress during pregnancy and sever nausea
and/or vomiting during the first trimester have been
implicated as potential risk factors in the development
of tic disorders [ 151. Tourette syndrome can harm a
child by impairing major life activities during the
child’s developmental stage in life, such as occupa-
tional, social and education impairments [ 171. Several
studies have shown that learning difficulties are com-
mon in children with TS and that tics are more
Correspondence: Najah Khalifa, Department of Neuroscience, Child and Adolescent Psychiatry, University Hospital, SE-75 1 85 Uppsala, Sweden. Tel: + 46 18
61 12550. Fax: +46 18 61 12565. E-mail: email@example.com
(Received 223itne 2004; revised I I February 2005 and 10 May ZOOS; accepted 31 May 200s)
ISSN 0803-5253 prindISSN 1651-2227 online f , 2005 Taylor & Francis
Tourette syndrome and other tic disorders
and school as the 25 children with TS. The mean age
was 10.4 y. Three control children did not accept
participation, and another three controls were selected
and accepted to participate. Two children (one boy and
one girl) with TS did not want to be interviewed
and examined. They were both known by the first and
second authors and gave their permission to use all
documents and medical records.
The children with chronic motor or vocal tics
included 18 girls and 40 boys. They had a mean age of
common in children attending special education
classes [6,7,18,19]. This was also found in our study,
where 0.6% of school children had TS and half of the
children in special school had tics . The symptoms
fluctuate markedly in severity and frequency over time,
and vary from one individual to another. This con-
tributes to frequent misdiagnoses. The symptoms
may sometimes be wrongly attributed to hyperactivity,
non-adequate habits, allergies, asthma and other
conditions [2 1,221.
Clinical populations are selected and might not
reflect problems in the general population. Thus, it is
important to investigate the background and symp-
toms from a total population. To our knowledge, no
controlled, population-based study of schoolchildren
with TS and other tic disorders has been published.
Most of the studies have been based on clinical samples
and some have not differentiated between Tourette
syndrome and simple tics. Knowledge with respect to
the background and clinical characteristics of different
tic disorders is essential for planning and early support
in healthcare and education.
The first aim of this study was to describe the symp-
toms and severity of Tourette syndrome and other tic
disorders, and the age of onset in a total population of
children. The second aim was to survey where children
with tics seek help for their behaviour problems. The
third aim was to study the familial loading of mental
disorders in first-degree relatives of children with
Tourette syndrome and other tic disorders. The fourth
aim was to evaluate the role of adverse pre- and peri-
natal events in the development of Tourette syndrome
and to compare socio-economic status between the
Material and methods
A total population of 4479 children aged 7-15 y and
their parents in a town in central Sweden were asked to
fill in a screening questionnaire covering both motor
and vocal tics. A three-stage procedure was used. The
first was a screening, the second an interview and the
third a clinical investigation. The parents who an-
swered that their children had possible tics (n=298)
were interviewed by the first author to confirm or refute
tic disorder. Eighty per cent of the children accepted a
face-to-face interview and a physical examination. For
details of the original study, see Khalifa and von
Tourette syndrome, according to the DSM-IV cri-
teria , was found in 25 (0.6%) children. Another 58
(1.3%) suffered from chronic motor or vocal tics, and
214 (4.8%) children had had transient tics in the last
year. All together, 297 (6.6%) children, 7-15 y, suf-
fered or had suffered from some kind of tic disorder.
Twenty-five controls without any tics, and 25 children
with transient tics were selected with the same age, sex
The parents of each child had a semi-structured
interview , which lasted-about 90 min. The inter-
view was longer if the child had major problems. It
was systematically focused on heredity, pregnancy,
obstetrical and neonatal circumstances, milestones of
development, current behaviour, and social as well
as ’motor performance. Social class was determined
using the classification of the Swedish Central Bureau
of Statistics , which takes account of the bread-
winner’s occupational status. The level of education of
the mother was also included in this study.
The child was present during the interview with the
parents and was observed and examined by the first
author (NK). The examination was comprised of a
routine paediatric examination such as weight, height,
head circumference, speech, language, activity level,
skull, mouth, lungs, heart, blood pressure, abdomen,
skin and puberty stage . A more detailed neuro-
logical and mental examination was carried out using a
modified version of the neurodevelopmental screening
test . The examination included the testing of
cranial nerves, fine motor skills, diadochokinesis,
standing on the left and right leg for 20 s, walking on
heels and toes, Fog’s test, Prechtl’s sign, the Romberg
test, jumping back and forth across a line, the fine
motor test, stereognosis, and Babinski and tendon
reflexes. Each of the items was scored on a scale of 0 to
2 (0 =no abnormality, 1 =some abnormality, and
2 = major abnormality).
The assessment involved a comprehensive interview-
based questionnaire of the medical history, including
heredity, and a clinical interview . Tic type and
severity were assessed by clinical examination and by
the Shapiro Tourette Severity Scale (TSSS) . The
scoring of tic severity range was from 0 (none) to 9
(very severe). Pregnancy, obstetrical and other relevant
medical records were collected concerning the 25
1 6 10
Table I. Modified Prechtl’s non-optimal score.
N. Khalifa & A. -L. von Knorring
Pre-, peri- and neonatal factors
Maternal age (y)
Abortions in history
Bleedings in pregnancy
Severe infections in pregnancy
Psychiatric specialist care
Maternal diabetes or epilepsy
Gestational age (wk)
Small for age
Twins or multiple birth
Breech, foot or other abnormal presentation
Cord prolapse/around neckknot
Child severely traumatized
(fractures, many petechiae)
Anaemia requiring transfusion
Irritable/floppy infant, convulsions
Difficulties regulating temperature
Oxygen treatment >30%
i l wk
children with Tourette syndrome and their matched
controls. The method used for rating “reduced
optimality in the pre-, peri- and neonatal periods” is
described in Gillberg and Gillberg , which is a
modified version of Prechtl’s list of optimal conditions
. For each factor with optimal conditions a score of
0 was given, and for each condition outside the optimal
range a score of 1 was given. All scores for individual
items were then added to obtain a total score for
reduced optimality in the pre-, peri- and neonatal
periods (Table I).
The study was approved by the Research Ethics Com-
mittee of the Medical Faculty, Uppsala University.
The statistical package SPSS for Macintosh 10.0 was
used. Comparisons of proportions between groups
were performed using x2 tests. Comparisons of mean
values were performed with ANOVA. The Pearson
correlation coefficient was used to examine the linear
association between variables. A significance level of
5% was used.
Onset and diagnosis
The first neurological symptoms of TS appeared
between 3 and 10 y of age (mean 4.6 f 2.9 y). The first
symptoms of children with CMT were observed at
7.4 f 2.6 y and CVT at 8.2 f 2.1 y (CMT versus CVT:
n.s.). The 25 matched children with transient tics had
onset of tics at 8.5 3.0 y. The age of onset of children
with TS was significantly lower than the age of onset of
chronic motor or chronic vocal tics (CMVT) (F = 13.4,
p=O.OOO). The average interval between the onset of
the first symptoms and when the diagnosis of TS was
made was 4 y, ranging from 1 to 8 y. Prior to the study,
three of the TS cases had been in contact with out-
patient services of child psychiatry clinics, six children
had been treated by a child neurologist and one child
had been treated by a paediatrician. Another 14 had
been in contact with at least two of the previously
serviceslspecialists. The children were referred wirh
different symptoms (Table 11).
Sixteen children (64%) were diagnosed with TS
prior to the study, but only three had TS as the only
diagnosis. Thirteen had more than two additional dia-
gnoses. Nine children were diagnosed during the study,
and eight of them had been in contact with medical
care. The only child without contact with medical
services was a sibling to a child already diagnosed as
suffering from Tourette syndrome. Children with TS
Table 11. Problems and initial symptoms at referral in children with Tourette syndrome, chronic motor tic, chronic vocal tic and transient tic
Chronic motor tics
Chronic vocal tics
Short attention spanihyperactivity
Specific developmental disorder
No contact with medical care
Tourette syndrome and other tic disorders
16 1 1
of CMVT. Eleven children with TS were taking med-
ication to relieve their symptoms. Two were treated
with stimulants, two with stimulants combined with
SSIU, two with SSRI only, one with valoprate, two with
antipsychotics, and two with clonidine. Twelve chil-
dren had undergone psychodynamic therapy, and two
had had behaviour modification therapy.
Table 111. Clinical diagnoses of the children with Tourette syndrome
preceding the start of the study.
Tourette syndrome plus other diagnoses
Language disturbance and obsessive-compulsive
Defiance and child-parent problems
No contact with medical care
had different diagnoses before the study, as can be seen
in Table 111.
In 18 (72%) of the cases with TS, the initial symptom
started with tics in the head and face. Vocalizations
were reported as the initial symptom in four (16%),
and it was mostly repeated throat clearing. At the time
of examination, all children with TS showed simple
tics. Blinking, facial grimacing and shoulder shrugging
appeared in 19 (76%) of the children with TS, 26
(76%) with CMT and 16 (64%) with TT. Complex
motor tics, e.g. jumping, trunk bending and head
shaking, were present in 10 (40%) with TS, 11 (32%)
with CMT and two (8%) with TT. Vocal tics were
predominantly of the simple type, such as sniffing,
throat clearing, blowing and whistling. The distribu-
tion of tics at the time of the examination can be seen in
Table I V .
Tic severity and treatment
The severity of tic symptoms was evaluated for each
child with the TSSS. Tic severity of children with TS
was significantly higher compared to other groups of tic
disorders. The mean score for TS was 5.0+ 1.9
(marked tic severity), CMT 1.4f 1.1 (mild) and TT
0.4f0.6 (very mild) (F=95.8, p=O.OOO). Children
with severe TS were younger at the onset of the dis-
order (Pearson corr. = 0.56, p = 0.004). N o significant
correlation was found between age of onset and severity
Family histo y
Questions about psychiatric illnesses were asked three
generations back. Eighty per cent of the first-degree
relatives of TS children reported some psychiatric ill-
ness. The most common were different tic disorders,
ADHD, OCD and depression. Only 20% of the control
children were reported to have first-degree relatives
with psychiatric illness (TS = 20 vs controls = 5;
x2= 18,p<0.001) (Table V).
Perinatal history and socio-economic status
Pregnancy, obstetrical and other relevant records were
collected concerning the children with TS and mat-
ched controls. One child with TS was adopted and
born abroad, and no record was available. There were
no statistical differences between the children with TS
and the control children with regards to reduced
optimality in the pre-, peri- and neonatal periods. The
mothers of children with TS were two times more likely
to have had complications during pregnancy
(Table VI) and were younger than control mothers
when they gave birth to the index child (mean 20f
1.4 y vs 23 f 3.4 y, p < 0.01). Socio-economic status,
parental education or divorce rate did not differ sig-
nificantly between the children with TS, CMT, CVT,
TT and controls.
To our knowledge, this study is the first controlled
population study of biological, predisposing, heredi-
tary, family and socio-economic factors of school-
children with Tourette syndrome and other tic
disorders. The onset of TS typically occurs at 4 to 5 y
Table IV. Type of tics and prevalence at the time of examination in children from a total population of 2 14 children with Tourette syndrome,
chronic motor tics, chronic vocal tics and transient tics. Twenty-five were matched with TS children for age, sex and school.
Chronic motor tics
Chronic vocal tics
Motor tics (simple and complex)
Eyes, face or head
Shoulder, neck, arm
Simple vocal tics
Complex vocal tics
Table V. Number of children with different tic disorders and matched controls who have a first-degree relative with psychiatric disorder.
N. Khalifa &A.-L. von Knom'ng
Tourette syndrome (TS) Chronic motor or vocal Transient tics (TT) Controls (C)
tics (CT) n=58 (%)
n = 25 (%)
Pervasive developmental disorders
***p<O.OOl, ** p<O.Ol, * p<0.05.
of age for children with TS and significantly later, at 7
to 8 y, for children with chronic motor or vocal tics.
Symptoms in the general population are similar to
those described in clinical populations. Children with
severe Tourette syndrome had a younger age of onset
of the disorder, but this correlation was not found in
CMVT. Retrospective information about the onset of
tic symptoms is not always totally reliable. However, it
is almost impossible to conduct a prospective study of
the onset of tics, as the majority of patients do not seek
help for the tics but rather for other problems. All
(96%) except one child with Tourette syndrome had
been in contact with medical services. About a third
had been in contact with child psychiatry prior to the
study, but surprisingly none of them had a diagnosis of
Tourette syndrome. It is well known from earlier
clinical descriptions that recognition and diagnosis of
tics and Tourette syndrome often occur very late
[21,22]. This was also the case in our study: e.g. 1/3
had no diagnosis of TS prior to the study, although they
had tried to find help for different kinds of symptoms
and problems. The results of our study give further
evidence of this. These findings draw attention to the
importance of conducting a careful neurological
assessment of children with behavioural and develop-
Less than half of the children with chronic tics and
only a minority with transient tics (1 2%) had sought
Table VI. Cumulative non-optimal pre-, peri and neonatal scores in
25 children with Tourette syndrome and 25 controls in clusters.
Factor Tourette syndrome Controls
Prenatal non-optimality score
Intrapartal non-optimality score
Neonatal non-optimality score
Total non-optimality score
Optimal condition = 0 for each factor; non-optimal condition = 1 for
help from medical services. One explanation for this
might be that the tics were mostly mild for children
with CMVT and very mild for those with TT. Contact
with health services was due to causes other than tics,
such as delayed psychomotor development, attention
problems and learning difficulties.
A high prevalence of psychiatric illness was found in
the family. This has also been reported in earlier studies
[7,8]. We found that 80% of first-degree relatives of TS
children had psychiatric illnesses. The most common
were different tic disorders, ADHD, OCD and
depression. The very high familial loading of tics and
OCD supports the earlier proposal that the cause of
Tourette syndrome is highly genetic. The most
important conclusion to be drawn on the basis of the
present results is that tic disorders run in families with a
high prevalence of psychiatric disorders, which draws
attention to the importance of thorough investigation
of the parents and siblings of patients with TS for
evidence of tics, OCD, depression or ADHD.
Family studies are never conclusive concerning the
genetic basis of disorders. In order to study genetic-
environmental factors, other methods are needed, i.e.
twin studies and molecular genetic studies.
No statistically significant increase of pre-, peri and
neonatal complications were found between children
with Tourette syndrome and matched controls in this
study. However, the proportion of pre- and neonatal
non-optimal circumstances was higher in TS children
than in the controls. Data were based on records from
pre- and neonatal care. Another study [ 151 discussed
that the degree of maternal stress and severity of nausea
and vomiting in the first trimester may be important.
O u r findings are in line with this. However, no control
group was used in Leckman's study, and it is not
possible to know whether perinatal factors are more
prevalent in TS than in the general population. No
differences in socio-economic circumstances were
found between the different tic disorders and con-
trols, which supports the hypothesis that genetic and
Tourette syndrome and other tic disorders
 Comings DE, Comings BG. A controlled family history
study of Tourette syndrome, I: Attention-deficit hyperactivity
disorder and learning disorders. J Clin Psychiatry 1990;7:
2 7 5-80.
 Comings DE, Comings BG. A controlled family history study
of Tourette syndrome, 111: Affective and other disorders. J Clin
 Robertson MM, Gourdie A. Familial Tourette’s syndrome in a
large British pedigree. Associated psychopathology, severity,
and potential for linkage analysis. Br J Psychiatry 1990;156:
[lo] Hanna PA, Janua FN, Contant CF, Janovic J. Bilineal
transmission in Tourette syndrome. Neurology 1999;4:
[l 11 Walkup JT, La Buda MC, Singer HS, Brown J, Riddle MA,
Hurko 0. Family study and segregation analysis of Tourette
syndrome evidence for a mixed model of inheritance. Am
J Hum Genet 1996;59:684-93.
 Leckman JF, Peterson BS, Andersen GM, Amsten AF, Pauls
DL, Cohen D. Pathogenesis bf Tourette syndrome. J Child
Psychol Psychiatry 1997;3:119-42.
[ 131 Kurlan R, Eapen V, Stem J, McDermott MP, Robertsson MM.
Bilineal transmission in Tourette’s syndrome families.
141 Leckman JF, Cohen DJ, Price RA, Riddle MA, Minderaa RB,
Anderson GM, et al. The pathogenesis of Tourette syndrome:
a review of data and hypotheses. In: Shah NS, Donald AG,
editors. Movement disorders. New York Plenum Press; 1986.
151 Leckman JF, Dolnansky ES, Hardin MT, Clubb M, Walkup
JT, Stevenson J, et al. Perinatal factors in the expression of
Tourette syndrome: an exploratory study. J Am Acad Child
Adolesc Psychiatry 1990;29:220-6.
 Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ,
Perlmutter S, et al. Pediatric autoimmune neuropsychiatric
disorders associated with streptococcal infections: Clinical
description of the first 50 cases. Am J Psychiatry 1998;155:
 Comings DE, Comings BG. Tourette syndrome; clinical and
psychological aspects of 250 cases. Am J Hum Genet
 Freeman RD,
Robertson MM, Sander P. Tourette Syndrome Intema-
tional Database Consortium, An international perspective
on Tourette syndrome. Selected findings from 3500 indi-
viduals in 22 countries. Dev Med Child Neurol
[ 191 Kurlan R. Tourette syndrome in special education population:
hypotheses. Adv Neurol 1992;58:78-81.
 Khalifa N, von Knorring AL. Prevalence of the tic disorders
and Tourette syndrome in a Swedish school population. Dev
Med Child Neurol 2003;45:3 15-3 1.
 Janovic J, Sekula SL, Milas D. Dermatological manifestations
of Tourette syndrome’s and obsessive-compulsive disorder.
Arch Dermatol 1998;134:113-4.
 Hogan MB, Wilson NW. Tourette syndrome mimicking
asthma. J Asthma 1999;36:253-6.
 American Psychiatric Association.
statistical manual of psychiatry of mental disorders, 4th ed.
(DSM-IV). Washington, DC: American Psychiatric Associa-
 Gillberg C, Rasmussen P. Perceptual, motor and attention
deficits in seven year-old children: Background factors. Dev
Med Child Neurol 1982;24:752-70.
 Swedish Central Bureau of Statistics. Socio-economic classi-
fication (in Swedish); 2002.
 Tanner JM. Growth at adolescence. Oxford: Blackwell Scien-
tific Publications; 1962.
Burd L, Kerbeshian J,
biological factors are important in the aetiology of tic
Despite the limitations of our study, its strength is
that it is based on a total population of schoolchildren.
One weakness of this study is the small sample size of
tic disorders. This may hide some of the differences
not found between the groups due to type-2 errors.
Another weakness is that one investigator (NK) made
all the diagnoses without any tests of reliability of the
different measurements. However, this is also a
strength in that evaluation is made in a consistent way.
Certain patients were also investigated by other phy-
sicians who confirmed the assessment. Forthcoming
reports will focus on comorbid psychiatric disorders
of children with Tourette syndrome and other tic
A high rate of psychiatric disorders is prevalent in
parents and siblings of children with Tourette syn-
drome. The findings of this study draw attention to the
importance of thorough investigation of both parents
and siblings of patients with TS for evidence of tics,
OCD, depression or ADHD. The neurological symp-
toms of Tourette syndrome start significantly earlier
than the symptoms of chronic motor tics. Tic severity is
correlated with early age of onset. In a total population
of children, almost all sought help from medical
We are grateful to all parents and children who participated.
This study has been made possible by support from the
Bermark‘s Foundation, the Professor Bror Gadelius’ Foun-
dation, and the Linnea and Josef Carlsson’s Foundation. We
are grateful to Margaretta Bratt, MD, for her clinical gui-
dance and support, Professor Claes Sundelin for his com-
ments, Steven Lucas, MD, who helped us with the language,
and Hans knell, for excellent guidance in the statistical
formation of the data. We also want to thank the Principals of
all the Primary Schools of Ludvika and Smedjebacken.
[ 11 Robertson MM. Annotation: Gilles de la Tourette syndrome -
an update. (Review). Br J Psychol Psychiatry 1994;35:
597-6 1 1.
 Lees AJ, Robertson MM, Trimble MR, Murray NM. A clinical
study of Gilles de la Tourette syndrome in the United King-
dom. J Neurology Neurosurg Psychiatry 1984;47: 1-8.
 Bruun RD, Budman CL. The course and prognosis ofTourette
syndrome. Neurol Clin 1997;15:291-8.
 Staley D, Wand R, Shady G. Tourette disorder: a cross-cultural
review. Compr Psychiatry 1997;38:6-16.
 Nomura Y, Segawa M. Tourette syndrome in oriental children:
clinical and pathophysiological consideration. Adv Neurol
 Comings DE, Himes JA, Comings BG. An epidemiological
study of Tourette Syndrome in a single school district. J Clin
A. -L. von Knom'ng
 Gillberg C. Children with minor developmental disorders.
Neurological and neurodevelopmental problems at age 10. Dev
Med Child Neurol 1985;27:3-16.
 Shapiro AK, Shapiro ES, Young JG, Feinberg TE. Gilles
de la Tourette syndrome. 2nd ed. New York Raven Press;
1988. p 451-80.
 Gillberg C, Gilberg IC.
population study of reduced optimality in the pre-,
pen-, and neonatal period. J Autism Dev Disord 1983;13:
 Prechtl HFR. The optimality concept. Early Hum Dev
Infantile autism: a total