Evidence for autosomal dominant transmission in Tourette's Syndrome–United Kingdom Cohort Study

National Hospital for Neurology and Neurosurgery, London.
The British Journal of Psychiatry (Impact Factor: 7.99). 06/1993; 162(5):593-6. DOI: 10.1192/bjp.162.5.593
Source: PubMed


Complex segregation analyses were performed on families ascertained through 40 unselected consecutive patients with Tourette's syndrome to examine the hypothesis that its transmission is consistent with genetic inheritance. Analyses were done using several diagnostic classifications. All results were consistent with an autosomal dominant gene with high penetrance. The penetrances ranged from 0.882 to 1.000 for males and 0.452 to 0.980 for females, depending upon the specific classification scheme incorporated into the analyses.

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    • "Clinical and epidemiological studies point to a very high incidence of other childhood onset behavioral and developmental disorders including up to 60% with ADHD and up to 50% with obsessive–compulsive disorder (OCD). It has long been suggested that chronic tics and OCD within TS families are likely manifestations of the same underlying genetic etiology with gender-dependent differences in expression leading to male members of the family exhibiting more tic behaviors and the female members exhibiting OCD (Eapen et al., 1993). Furthermore, recent SNP association data suggests that OCD in the presence of TS/Chronic tics may have different underlying genetic susceptibility compared to OCD alone (Eapen et al., 1993). "
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    ABSTRACT: Autism spectrum disorder (ASD) is characterized by a broad spectrum of behavioral deficits of unknown etiology. ASD associated mutations implicate numerous neurological pathways including a common association with the neurexin trans-synaptic connexus (NTSC) which regulates neuronal cell-adhesion, neuronal circuitry, and neurotransmission. Comparable DNA lesions affecting the NTSC, however, associate with a diversity of behavioral deficits within and without the autism spectrum including a very strong association with Tourette syndrome. The NTSC is comprised of numerous post-synaptic ligands competing for trans-synaptic connection with one of the many different neurexin receptors yet no apparent association exists between specific NTSC molecules/complexes and specific behavioral deficits. Together these findings indicate a fundamental role for NTSC-balance in stabilizing pre-behavioral control. Further molecular and clinical characterization and stratification of ASD and TS on the basis of NTSC status will help elucidate the molecular basis of behavior - and define how the NTSC functions in combination with other molecular determinates to strengthen behavioral control and specify behavioral deficits.
    Full-text · Article · Feb 2014 · Frontiers in Human Neuroscience
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    • "Thus it would seem that instead of changing the definition and criteria to achieve the various goals and functions, we need to strive for further refinement in categorizing and subtyping autism within the dimensional framework. It would be a great help if nosology of developmental disorders can facilitate the diagnostician through subtyping based on family history , neuro-cognitive characteristics, or symptom dimensions which would then allow early identification using behavioral telltale signs and genetic testing, choice of difference in the expression of the underlying genotype with female members of the family presenting with OCB and male members with tics (Eapen et al., 1993). It has also been shown that there are sex-specific differences in the topographic segregation and functionality of brain regions and that the presence of circulating testosterone is essential for the development of the substantia nigra region in the neonatal period and to a lesser extent in the final maturation in the peripubertal period (Veliskova and Moshe, 2001). "

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    • "obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) [Como, 2001]. The etiopathogenesis of TS is still unclear, although it has long been suspected that this is a heritable condition [Eapen et al., 1993; Pauls, 2003]. However, other mechanisms related to autoimmunity and beta-hemolytic streptococcal infections have also been implicated as a causative mechanism [Mell et al., 2005; Pauls, 2003; Swedo et al., 1998]. "
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    ABSTRACT: The fronto-striato-thalamic circuit has been implicated in the pathomechanism of Tourette Syndrome (TS). To study white and gray matter comprehensively, we used a novel technique called Tract-Based Spatial Statistics (TBSS) combined with voxel-based analysis (VBA) of diffusion tensor MR images in children with TS as compared to typically developing controls. These automated and unbiased methods allow analysis of cerebral white matter and gray matter regions. We compared 15 right-handed children with TS (mean age: 11.6 ± 2.5 years, 12 males) to 14 age-matched right-handed healthy controls (NC; mean age: 12.29 ± 3.2 years, 6 males). Tic severity and neurobehavioral scores were correlated with FA and ADC values in regions found abnormal by these methods. For white matter, TBSS analysis showed regions of increased ADC in the corticostriatal projection pathways including left external capsule and left and right subcallosal fasciculus pathway in TS group compared to NC group. Within the TS group, ADC for the left external capsule was negatively associated with tic severity (r= -0.586, P = 0.02). For gray matter, VBA revealed increased ADC for bilateral orbitofrontal cortex, left putamen, and left insular cortex. ADC for the right and left orbitofrontal cortex was highly correlated with internalizing problems (r = 0.665; P = 0.009, r = 0.545; P = 0.04, respectively). Altogether, this analysis revealed focal diffusion abnormalities in the corticostriatal pathway and in gray matter structures involved in the fronto-striatal circuit in TS. These diffusion abnormalities could serve as a neuroimaging marker related to tic severity and neurobehavioral abnormalities in TS subjects.
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