We have expanded the clinical spectrum of autosomal recessive variants by describing a syndrome with features overlapping CS/CISS1 and BOS.

Interstitial deletions of chromosome 3p are rare, and specific genotype-phenotype correlations cannot always be assessed. We report the case of a 3p14.2 proximal microdeletion in a 60-year-old female patient with mild intellectual disability, severe speech delay, and mild dysmorphism. An array-CGH analysis detected a 500-kb deletion in the 3p14.2 region, including FEZF2, CADPS, and PTPRG. FEZF2 and CADPS are known to network within the neurodevelopmental pathways. It is possible that their rearrangements lead to the phenotypic features observed in the patient, and therefore, they can be considered candidate genes responsible for such abnormalities.

Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all sudden cardiac death cases in individuals with a structurally normal heart. Pathogenic variants associated with Brugada syndrome have been identified in over 19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In contrast to other arrhythmogenic channelopathies (such as long QT syndrome), digenic inheritance has never been reported in Brugada syndrome. Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient. The parents were heterozygous for each variation. This novel finding highlights the role of mutation load in Brugada syndrome and strongly suggests the adoption of a gene panel to obtain an accurate genetic diagnosis, which is mandatory for risk stratification, prevention, and therapy.

The proportion of cases with additional risk factors is smaller than reported in previous studies, but it remains substantial and confirms the need for strategies to increase awareness of the public and health professionals responsible for the care of women in childbearing age.

We produced a short digital film on telegenetic counseling for pregnant women of advanced maternal age. Reasoning that the increasing number of women and couples requiring genetic testing, many of whom will not have easy access to counseling centers, need a standardized, reliable approach, we explain the genetic risks associated with advanced maternal age, as well as possible preventive measures, prenatal testing procedures (both invasive and noninvasive), laboratory assessment methods (stating the specificity and accuracy of the available tests), and best-practice communication of results. We also explain any possible causes of test failure and stress the role of the medical geneticist and the importance of effective communication during genetic counseling. This video is freely available in both English and Italian (www.ospfe.it/geneticamedica). It is our hope that this initiative will facilitate communication among geneticists, obstetricians, pregnant women, and all stakehold ers involved in prenatal care and diagnosis