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Tourettes syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P

Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P

OBJECTIVE: Substantial evidence suggests that both environmental and genetic factors contribute to the development and clinical expression of Tourette's syndrome. Although genetic studies of Tourette's syndrome are common, studies of environmental factors are relatively few and have not identified consistent risk factors across studies. This study examines in a large cohort of subjects (N=180) the relationship between prenatal/perinatal adverse events with Tourette's syndrome severity as determined by tic severity and rates of commonly comorbid disorders such as obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and self-injurious behavior. METHOD: Tic severity, OCD, ADHD, self-injurious behavior, and exposure to a variety of prenatal/perinatal events were systematically assessed in all subjects enrolled in three genetic studies of Tourette's syndrome. Using linear and logistic regression, a best-fit model was determined for each outcome of interest. RESULTS: Prenatal maternal smoking was strongly correlated with increased tic severity and with the presence of comorbid OCD in these Tourette's syndrome subjects. Other variables, such as paternal age and subject's birth weight, were significantly but less strongly associated with increased symptom severity. The authors found no association between symptom severity and hypoxia, forceps delivery, or hyperemesis during pregnancy, which have been previously identified as risk factors. CONCLUSIONS: This study identifies prenatal maternal smoking as a strong risk factor for increased symptom severity in Tourette's syndrome. [ABSTRACT FROM AUTHOR]

Spontaneous cerebellar haematomas in previously well children are most often caused by haemorrhage from small angiomas. Eight such cases in children 12 years of age or younger have been reported previously. Their clinical course was usually not as acute as the course most commonly seen in adults, and four of the children survived after evacuation of the haematoma. Two additional cases are presented. Both children were admitted in a comatose state, but survived after surgical intervention. Cerebellar haematomas in children seem to have a better prognosis than in adults and should be considered in the evaluation of children with subarachnoid haemorrhage or the rapid onset of coma. Even if admitted in extremis, recovery is possible after prompt diagnosis and surgical evacuation of the haematoma. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to characterize the clinical features, course, and treatment of essential tremor (ET) in children., Methods: A retrospective chart review was conducted over 25 years (1984-2011). Inclusion criteria were age <21 years and satisfying the core diagnostic criteria for ET. Primary exclusion criteria included other neurological findings, tremorogenic medications, sudden onset/stepwise progression, primary orthostatic tremor, and isolated task specificity; and secondary exclusion criteria were abnormal neuroimaging or metabolic/thyroid studies. Cases were reviewed for age, sex, family history, tremor characteristics, functional impairment, treatment, and follow-up., Results: In total, 211 children had ET, including 130 males and 81 females. The mean ± standard deviation age was at diagnosis was 14.09 ± 5.0 years, the age of onset was 9.71 ± 5.62 years, and the age of onset was birth in 7 children. One hundred ninety-nine children had bilateral hand tremor, 34 had asymmetry, 9 had unilateral onset but later became bilateral. Twelve children had voice tremors, 13 had leg tremors, 5 had head tremors, and 7 had trunk tremors. Tremor at rest was present in 20 children. Thirty-five percent of the children had a family history of ET, including in a father (n = 21), mother (n = 13), brother (n = 6), sister (n = 3), and other family member (n = 28). Fifty-five percent of patients had functional disabilities, including writing (n = 66), eating (n = 28) drinking from a cup (n = 13), typing (n = 4), playing instruments (n = 6), buttoning (n = 6), and playing (n = 3). For treatment, 33 patients received propranolol, 1 received atenolol, 13 received primidone, 3 received metoprolol, and 1 received nadolol. In total, 99 patients were followed for a mean ± standard deviation of 1.82 ± 2.21 years.If left untreated, tremor remained unchanged in 33 patients, and 7 had an apparent short-term improvement. On propranolol, 15 of 20 patients significantly improved., Conclusions: This is the largest series to date of ET in children. The current findings indicate that onset at birth is possible, family history is less common in children than in adults, and tremor at rest is possible. Functional disability was noted in 55% of children, and 29.4% required medication.

Background: The objective of this study was to determine the frequency, nature, and impact of sleep disorders in children and adolescents with Tourette syndrome and to raise awareness about their possible inclusion as a Tourette syndrome comorbidity., Methods: Using a prospective questionnaire, we interviewed 123 patients of age ≤21 years with a confirmed diagnosis of Tourette syndrome. Each completed questionnaire was then reviewed in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for categorization to a form of sleep disorder., Results: Of the 123 patients with Tourette syndrome, 75 (61%) had comorbid attention deficit hyperactivity disorder and 48 (39%) had Tourette without attention deficit hyperactivity disorder. The sleep problems observed included problems in the nature of sleep, abnormal behaviors during sleep, and impact of sleep disturbances on quality of life. Within these cohorts, 31 (65%) of the 48 Tourette-only patients and 48 (64%) of the 75 Tourette + attention deficit hyperactivity disorder patients could fit into some form of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, coded sleep disorders. Of the 48 Tourette + attention deficit hyperactivity disorder patients with sleep disorders, 36 (75%) had insomnia signs, which could be explained by the co-occurrence of attention deficit hyperactivity disorder and high stimulant use. However, 10 (32%) of the 31 Tourette-only patients with sleep disorders had insomnia irrespective of attention deficit hyperactivity disorder or medication use., Conclusions: Sleep problems are common in children with Tourette syndrome irrespective of comorbid attention deficit hyperactivity disorder, justifying their inclusion as a comorbidity of Tourette syndrome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study compares primary stereotypies (repetitive, self-stimulating, and seemingly nonsensical movements that can occur within typically developing children) and secondary stereotypies (those occurring within autistic or mentally retarded children). Utilizing a retrospective chart review from 1995 to 2010, the current study compares primary and secondary stereotypies by the application of a classification system that organizes the movement by its type (motor only, phonic only, mixed) and complexity. In addition, it investigates other parameters associated with the movements such as duration, frequency, age, functional impairment, and progression. The sample group consisted of 28 primary and 28 secondary cases. Primary stereotypies were predominantly motor, simple, of shorter duration, and of less frequency, whereas secondary stereotypies had more vocalization, complexity, longer durations, and higher frequencies. Moreover, functional impairment due to stereotypies was noted in 3 primary and 7 secondary cases, and worsening of stereotypies was noted in 70% of primary versus 44% of secondary cases.

Objective: The authors analyzed the frequency of occurrence of headaches in children and adolescents with Tourette syndrome (TS) to address their possible inclusion as a comorbidity., Study Design: Using a prospective questionnaire, administered directly, we interviewed a total sample size of 109 patients with TS ≤ 21 years of age. The questionnaires were then analyzed according to the International Headache Society's diagnostic criteria., Results: We found headaches to be present in 55% of the patients, with the 2 most common headache types being migraine headaches and tension-type headaches. The rate of migraine headache within the TS group was found to be 4 times greater than that of the general pediatric population, as reported in the literature. In addition, the rate of tension-type headache was found to be more than 5 times greater than that of the general pediatric population., Conclusions: Overall, the high rates of migraine and tension-type headache within this population support the proposition that headaches are a comorbidity of TS., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Tourette Syndrome (TS) has a complex etiology and wide variability in phenotypic expression. Identifying underlying symptom patterns may be useful for etiological and outcome studies of TS., Methods: Lifetime tic and related symptom data were collected between 1996 and 2001 in 121 TS subjects from the Central Valley of Costa Rica and 133 TS subjects from the Ashkenazi Jewish (AS) population in the US. Subjects were grouped by tic symptoms using an agglomerative hierarchical cluster analysis. Cluster membership was tested for association with available ancillary information (age of onset, tic severity, comorbid disorders, medication treatment and family history)., Results: Cluster analysis identified two distinct groups in each sample, those with predominantly simple tics (cluster 1), and those with multiple complex tics (cluster 2). Membership in cluster 2 was correlated with increased tic severity, global impairment, medication treatment, and presence of comorbid obsessive-compulsive symptoms in both samples, and with family history of tics, lower verbal IQ, earlier age of onset, and comorbid obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in the AS sample., Conclusions: This study provides evidence for consistent and reproducible symptom profiles in two independent TS study samples. These findings have implications for etiological studies of TS.

Rare sequence variants may be important in understanding the biology of common diseases, but clearly establishing their association with disease is often difficult. Association studies of such variants are becoming increasingly common as large-scale sequence analysis of candidate genes has become feasible. A recent report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette Syndrome (TS). The statistical evidence for this suggestion came from association analyses of a rare 3'-UTR variant, var321, which was observed in two patients but not observed in more than 2000 controls. We genotyped 307 Costa Rican and 515 Ashkenazi individuals (TS probands and their parents) and observed var321 in five independent Ashkenazi parents, two of whom did not transmit this variant to their affected child. Furthermore, we identified var321 in one subject from an Ashkenazi control sample. Our findings do not support the previously reported association and suggest that var321 is overrepresented among Ashkenazi Jews compared with other populations of European origin. The results further suggest that overrepresentation of rare variants in a specific ethnic group may complicate the interpretation of association analyses of such variants, highlighting the particular importance of precisely matching case and control populations for association analyses of rare variants.