The long QT syndromes (LQTS) are Mendelian inherited conditions where syncope and sudden death are due to precipitous occurrence of polymorphic ventricular tachycardia. In South Africa a number of white, some coloured and some Asian individuals have been identified but, interestingly, not a single black person and neither has it been reported from Africa. With over 400 known causal-mutations, mostly in cardiac ion channel-genes, it is unlikely to be absent in African populations. LQTS is notorious for going undiagnosed or misdiagnosed, perhaps even more so in Africa. Amongst persons of Afrikaner descent the KCNQ1 A341V-mutation represents a founder effect. The availability of 170 living individuals sharing the same mutation has made it possible to study factors modifying risk. A blunted autonomic response has been shown to decrease risk of attacks.

The presence of founder effects in South Africa for many single-gene diseases, which include heart diseases such as progressive familial heart block types I and II, hypertrophic cardiomyopathy and the long QT syndromes, afforded us the opportunity to identify causal genes and associated mutations through genetic mapping and positional cloning. From finding the genes, the emphasis has shifted to elucidating how primary defects cause disease and recognising factors that could explain the often pronounced phenotypic variability seen in persons carrying the same inherited defect. In some of these diseases, sudden unexpected death has been a frequent occurrence in young, apparently healthy individuals who had not been aware that they had inherited an underlying risk. Herein, we review progress in identifying genes, mutations and risk factors associated with the diseases mentioned.

A link between dissociation proneness in adulthood and self-reports of childhood traumatic events (including familial loss in childhood, sexual/physical abuse and neglect) has been documented. Several studies have also provided evidence for an association between dissociative experiences and trauma in patients with various psychiatric disorders, including post-traumatic stress disorder, borderline personality, dissociative identity and eating disorders. Based on the relative paucity of data on dissociation and trauma in obsessive-compulsive disorder (OCD) and trichotillomania (TTM), the primary objective of this study was to examine the relationship between trauma and dissociative experiences (DE) in these two diagnostic groups. Furthermore, the availability of clinical and genetic data on this sample allowed us to explore clinical and genetic factors relevant to this association. A total of 110 OCD and 32 TTM patients were compared with respect to the degree of dissociation (using the Dissociative Experiences Scale [DES]) and childhood trauma (using the Childhood Trauma Questionnaire [CTQ]). Patients were classified on the DES as either “high” (mean DES score ≥ 30) or “low” (mean DES score < 30) dissociators. Additional clinical and genetic factors were also explored with chi-square and t tests as appropriate. A total of 15.8% of OCD patients and 18.8% of TTM patients were high dissociators. OCD and TTM groups were comparable on DES and CTQ total scores, and in both OCD and TTM groups, significant positive correlations were found between mean DES scores and mean CTQ subscores of emotional abuse, physical abuse, sexual abuse, and physical neglect. In the OCD group, high dissociators were significantly younger than low dissociators, and significantly more high dissociators than low dissociators reported a lifetime (current and past) history of tics (P < .001), Tourette’s syndrome (P = .019), bulimia nervosa (P = .003), and borderline personality disorder (P = .027). In the TTM group, significantly more high dissociators than low dissociators reported (lifetime) kleptomania (P = .005) and depersonalisation disorder (P = .005). In the Caucasian OCD patients (n = 114), investigation of genetic polymorphisms involved in monoamine function revealed no significant differences between high and low dissociator groups. This study demonstrates a link between childhood trauma and DE in patients with OCD and TTM. High dissociative symptomatology may be present in a substantial proportion of patients diagnosed with these disorders. High dissociators may also be differentiated from low dissociators on some demographic features (e.g., lower age) and comorbidity profile (e.g., increased incidence of impulse dyscontrol disorders). Additional work is necessary before conclusions about the role of monoaminergic systems in mediating such dissociation can be drawn.

Background: There is increasing recognition that obsessive-compulsive disorder (OCD) is not a homogeneous entity. It has been suggested that gender may contribute to the clinical and biological heterogeneity of OCD. Methods: Two hundred and twenty patients (n = 220; 107 male, 113 female) with DSM-IV OCD (age: 36.40 +/- 13.46) underwent structured interviews. A subset of Caucasian subjects (n = 178), including subjects from the genetically homogeneous Afrikaner population (n = 81), and of matched control subjects (n = 161), was genotyped for polymorphisms in genes involved in monoamine function. Clinical and genetic data were statistically analyzed across gender. Results: Compared with females, males with OCD (1) had an earlier age of onset, and a trend toward having more tics and worse outcome, (2) had somewhat differing patterns of OCD symptomatology and axis I comorbidity, and (3) in the Caucasian group, were more likely to have the high activity T allele of the EcoRV variant of the monoamine oxidase A (MAO-A) gene compared to controls, and (4) in the Afrikaner subgroup, were more frequently homozygous for the G allele at the G861C variant of the 5HT(1Dbeta) gene than controls. Females with OCD (1) reported more sexual abuse during childhood than males, (2) often noted changes in obsessive-compulsive symptoms in the premenstrual/menstrual period as well as during/shortly after pregnancy, and with menopause, and (3) in the Caucasian subgroup, were more frequently homozygous for the low activity C allele of the EcoRV variant of the MAO-A gene compared to controls, with this allele also more frequent in female patients than controls. Conclusion: This study supports the hypothesis that gender contributes to the clinical and biological heterogeneity of OCD. A sexually dimorphic pattern of genetic susceptibility to OCD may be present. Further work is, however, needed to delineate the mechanisms that are responsible for mediating the effects of gender. (C) 2003 Elsevier B.V. and ECNP. All rights reserved.

There is increasing evidence that obsessive–compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

Objective: We investigate the role of functional variants in the catecholamine-O-methyl transferase gene ( COMT) and the monoamine oxidase-A gene ( MOA-A), as well as previously identified non-genetic risk factors in the manifestation of violent behaviour in South African male schizophrenia patients. Method: A cohort of 70 acutely relapsed male schizophrenia patients was stratified into violent and non-violent subsets, based on the presence or absence of previous or current violent behaviour. Standardized violence rating scales were also applied and the COMT/NlaIII and MAO-A promoter region variable number of tandem repeats (VNTR) polymorphisms were genotyped. Results: A multiple logistic regression model based on the clinical, genetic and sociodemographic variables indicated that delusions of control (OR = 3.7, 95% CI = 1.21–11.61) and the combined use of cannabis and alcohol (OR = 6.89, 95% CI = 1.28–37.05) were two significant predictors of violent behaviour in this schizophrenia population. No association was found between the tested polymorphisms and violent behaviour. Conclusions: Although the sample size may have limited power to exclude a minor role for these specific gene variants, such a small contribution would have limited clinical relevance given the strong significance of the non-genetic markers. These findings suggest that currently proactive management of violent behaviour in this schizophrenia population should continue to be based on clinical predictors of violence.

An evaluation of a 38-year-old Caucasian woman, who was referred to Tygerberg Hospital (Western Cape Province, RSA) with Wenckebach second-degree or possibly complete atrioventricular (AV) block that had progressed from first-degree AV block, identified a family history of the cardiac conduction system disorder progressive familial heart block type II (PFHBII). This prompted a retrospective clinical review of the subjects described in the original study, as well as additional family members who had not been examined in the original study. Progression of clinical features was observed, but more importantly, PFHBII was clinically redefined as an AV nodal disorder, which may progress to dilated cardiomyopathy (DCM).