Development and Pilot Implementation of the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) Intervention in Mexico.

PURPOSE: Genomic cancer risk assessment (GCRA) is standard-of-care practice that uses genomic tools to identify individuals with increased cancer risk, enabling screening for early detection and cancer prevention interventions. GCRA is not available in most of Mexico, where breast cancer (BC) is the leading cause of cancer death and ovarian cancer has a high mortality rate. METHODS: Guided by an implementation science framework, we piloted the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) intervention, combining GCRA training, practice support, and low-cost BRCA1/2 (BRCA) gene testing at four centers in Mexico. The RE-AIM model was adapted to evaluate GRACIAS intervention outcomes, including reach, the proportion of new patients meeting adapted National Comprehensive Cancer Network criteria who participated in GCRA. Barriers to GCRA were identified through roundtable sessions and semistructured interviews. RESULTS: Eleven clinicians were trained across four sites. Mean pre-post knowledge score increased from 60% to 67.2% (range 53%-86%). GCRA self-efficacy scores increased by 31% (95% CI, 6.47 to 55.54; P = .02). Participant feedback recommended Spanish content to improve learning. GRACIAS promoted reach at all sites: 77% in Universidad de Guadalajara, 86% in Instituto Nacional de Cancerología, 90% in Tecnológico de Monterrey, and 77% in Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Overall, a pathogenic BRCA variant was identified in 15.6% (195 of 1,253) of patients. All trainees continue to provide GCRA and address barriers to care. CONCLUSION: We describe the first project to use implementation science methods to develop and deliver an innovative multicomponent implementation intervention, combining low-cost BRCA testing, comprehensive GCRA training, and practice support in Mexico. Scale-up of the GRACIAS intervention will promote risk-appropriate care, cancer prevention, and reduction in related mortality.

Subtelomeric 6p monosomy and 12q trisomy in a patient with a 46,XX,der(6)t(6;12)(p25.3;q24.31) karyotype: Phenotypic overlap with Mutchinick syndrome.

We report on a patient with partial monosomy 6p and partial trisomy 12q identified by fluorescent in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH). She had a complex phenotype characterized by mental retardation (MR), psychomotor developmental delay, speech disorder, hypertelorism, eye anomalies, hearing loss, low-set malformed ears, thin upper lip, heart defect, clinodactyly, pes valgus, and skeletal anomalies. There is phenotypic overlap between our case and Mutchinick syndrome. This is the first report of a combined partial monosomy 6p and partial trisomy 12q due to an unbalanced translocation between subtelomeric regions of these chromosomes.

[Diabetes, pregnancy and birth defects]. / Diabetes, embarazo y defectos al nacimiento.

BACKGROUND: Diabetes mellitus affects 3 to 10% of pregnant women. The reported frequency of congenital malformations (CM) in diabetic mothers is 5.5 to 10%, contributing these defects to approximately 40% of the neonatal mortality in children of diabetic mothers (CDM). OBJECTIVE: To investigate the frequency and type of congenital malformations in a sample of livebirths of diabetic mothers from the Mexican population. MATERIAL AND METHODS: The analyzed information was obtained from the RYVEMCE (Registro y Vigilancia Epidemiológica de Malformaciones Congénitas). We analysed the type and frequency of the different CM diagnosed. These frequencies were compared with the whole amount of those CM included in the database of our registry (20,381). As part of the analysis, other maternal and neonatal variables were also compared between CDM and the control group. RESULTS: A total of 314 CDM (0.77%), 234 malformed and 80 non malformed were identified. The frequencies of cleft palate (CP), limb reduction defect (LRD) and microcephaly (MIC) were significantly higher in CDM than in the rest of malformed newborns of not diabetic mothers of the RYVEMCE (OR: 9.9, 3.8 and 10.0, respectively). A higher frequency of macrosomia was observed in CDM (18.0%) than in controls (6.1%), OR: 3.4, p < 0.001, in the frequency of preterm birth (28.5% than controls 13.0%), OR: 3.02, p < 0.0001 and in caesarean delivery (71.5% than controls 44.4%) OR: 3.15, p < 0.00001. CONCLUSIONS: Our results confirm the higher frequency of CM in CDM and in particular a higher risk for CP, LRD and MIC. Pregnancy and delivery complications such as macrosomia and preterm and caesarean delivery were also more frequent in CDM that controls. Certain associations of CM not described previously, were observed in the studied sample. Our results confirm the need of pregnancy planning including a pre-gestational and gestational control of maternal glycaemia, particularly in a population with such a high prevalence of diabetes mellitus as the observed in the Mexican one.