Epidemiological overview of multidimensional chromosomal and genome toxicity of cannabis exposure in congenital anomalies and cancer development

Cannabis and cannabinoids are implicated in multiple genotoxic, epigenotoxic and chromosomal-toxic mechanisms and interact with several morphogenic pathways, likely underpinning previous reports of links between cannabis and congenital anomalies and heritable tumours. However the effects of cannabinoid genotoxicity have not been assessed on whole populations and formal consideration of effects as a broadly acting genotoxin remain unexplored. Our study addressed these knowledge gaps in USA datasets. Cancer data from CDC, drug exposure data from National Survey of Drug Use and Health 2003–2017 and congenital anomaly data from National Birth Defects Prevention Network were used. We show that cannabis, THC cannabigerol and cannabichromene exposure fulfill causal criteria towards first Principal Components of both: (A) Down syndrome, Trisomies 18 and 13, Turner syndrome, Deletion 22q11.2, and (B) thyroid, liver, breast and pancreatic cancers and acute myeloid leukaemia, have mostly medium to large effect sizes, are robust to adjustment for ethnicity, other drugs and income in inverse probability-weighted models, show prominent non-linear effects, have 55/56 e-Values > 1.25, and are exacerbated by cannabis liberalization (P = 9.67 × 10–43, 2.66 × 10–15). The results confirm experimental studies showing that cannabinoids are an important cause of community-wide genotoxicity impacting both birth defect and cancer epidemiology at the chromosomal hundred-megabase level.

Prenatal diagnosis of Di George syndrome of the fetus with tetralogy of Fallot

Prenatal diagnosis of deletion 22q11.2 of the fetus in the second trimester of pregnancy, suspected on the basis of congenital heart disease (tetralogy of Fallot) in the combination with thymus hypoplasia, is presented. The pregnancy was interrupted.

Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations

Genetic risk for psychiatric illness is complex, so identification of shared molecular pathways where distinct forms of genetic risk might coincide is of substantial interest. A growing body of genetic and genomic studies suggest that such shared molecular pathways exist across disorders with different clinical presentations, such as schizophrenia and autism spectrum disorder (ASD). But how this relates to specific genetic risk factors is unknown. Further, whether some of the molecular changes identified in brain relate to potentially confounding antemortem or post-mortem factors is difficult to prove. We analyzed the transcriptome from the cortex and hippocampus of three mouse lines modeling human copy number variants (CNVs) associated with schizophrenia and ASD: Df(h15q13)/+, Df(h22q11)/+, and Df(h1q21)/+ which carry the 15q13.3 deletion, 22q11.2 deletion, and 1q21.1 deletion, respectively. Although we found very little overlap of differential expression at the level of individual genes, gene network analysis identified two modules of co-expressed genes that were dysregulated across all three mouse models. One module observed in both cortex and hippocampus was associated with neuronal energetics and firing rate, and overlapped with changes identified in post mortem human brain from SCZ and ASD patients. These data highlight aspects of convergent gene expression in mouse models harboring major risk alleles, and strengthen the connection between neuronal energetic dysfunction and neuropsychiatric disorders in humans.

Nieprawidłowości układu sercowo-naczyniowego w najczęściej występujących zespołach genetycznych u dzieci

Congenital cardiovascular pathology are the most frequent congenital pathologies diagnosed in children and they have an impact on morbidity, mortality and quality of life. About 15-30% of congenital heart malformations are the part of genetic syndromes. Early diagnosis plays a crucial role, specially in life threatening cardiovascular anomalies. Authors discuss the type of cardiovascular pathologies in Down, Turner, Noonan, Williams and deletion 22q11.2 syndromes. Left to right shunt pathology, which lead to the heart failure and pulmonary hypertension, are typical for Down syndrome. Complete form of atrioventricular septal defect is the most sever form of left to right shunt pathologies and is indication for early operation. In Turner syndrome bicuspid aortic valve and aortic coarctation are the most frequent. Noonan syndrome is coexisting with pulmonic valve stenosis, hypertrophic cardiomyopathy and atrial septal defect. Conotruncal anomaly (cyanotic heart pathology) and interrupted aortic arch type B are seen in deletion 22q11.2 syndrome. In Williams syndrome supravalvular aortic stenosis and peripheral pulmonary stenosis are the most frequent. Comprehensive multidisciplinary follow up is very important for those patients.

Pertinence d’un groupe d’affirmation de soi pour des personnes porteuses d’une délétion 22q11.2

L’affirmation de soi fait partie des techniques d’orientation cognitivo-comportementale visant à développer les aptitudes nécessaires pour communiquer de façon adaptée, en tenant compte des codes sociaux consensuels. Elle permet de prévaloir ses droits comme : savoir dire NON, prendre des décisions et gérer leurs conséquences. Cette technique a fait ses preuves auprès de personnes dépressives ou anxieuses, ayant un déficit de l’affirmation de soi et auprès de personnes psychotiques [1] présentant des difficultés à se mettre à la place de l’autre, ce qui entraîne des interprétations erronées et un évitement relationnel. La microdélétion 22q11.2 est une affection cytogénétique. Les troubles du comportement font partie des manifestations les plus fréquentes. Les personnes porteuses de la microdélétion peuvent rencontrer des difficultés pour communiquer avec les autres. Des troubles psychiatriques et de la cognition sociale [3] sont également documentés. D’après Jalbrzikowski et al. [2], ces derniers sont un puissant prédicteur de l’apparition de symptômes positifs. Face à ce constat-là, aider ces personnes à développer leurs compétences relationnelles, pour améliorer leur qualité de vie ou prévenir l’apparition de troubles psychiatriques, nous semble pertinent. Nous avons travaillé à l’adaptation d’un groupe d’affirmation de soi pour les personnes présentant une délétion 22q11.2. Nous animons un groupe hebdomadaire d’affirmation de soi pour cinq jeunes femmes. Les premières séances privilégient la définition des objectifs de chacune et une introduction aux habiletés conversationnelles. Les séances suivantes sont centrées sur la résolution de problèmes interpersonnels, avec jeux de rôles encadrés sur des situations apportées par les participantes. Entre chaque séance, des tâches à domicile sont données. Au-delà des améliorations cliniquement observées, nous présenterons les scores des participantes aux échelles d’évaluation pré- et post-groupe : [échelle des standards personnels de (Frost, 1990), échelle des croyances dysfonctionnelles (Bouvard et al., 1994)].Pour en savoir plusChambon O, et al. Ther Comportementale Cognit 1993;3:78–83.