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Weiss-Kruszka syndrome (WKS) is a rare genetic disorder characterized by metopic ridging, ptosis, arched eyebrows, down slanting palpebral fissures, abnormalities in the corpus callosum, cardiac malformations, and variable neurodevelopmental delay. To date, 32 individuals with a diagnosis of WKS have been reported in the literature. The syndrome is caused by a heterozygous pathogenic variant in the ZNF462 gene or a deletion of the 9p31.2 region involving ZNF462. There is significant phenotypic heterogeneity and intrafamilial variability among these patients. Our study reviewed nine patients from seven unrelated families and identified seven novel heterozygous ZNF462 variants through exome sequencing. GestaltMatcher analysis of our cohort's facial images, alongside previously published images of ZNF462 patients, demonstrated a high degree of facial similarity. Further longitudinal research is needed to delineate this rare condition's long-term health implications and adult-onset features., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Population medical genetics aims at translating clinically relevant findings from recent studies of large cohorts into healthcare for individuals. Genetic counseling concerning reproductive risks and options is still mainly based on family history, and consanguinity is viewed to increase the risk for recessive diseases regardless of the demographics. However, in an increasingly multi-ethnic society with diverse approaches to partner selection, healthcare professionals should also sharpen their intuition for the influence of different mating schemes in non-equilibrium dynamics. We, therefore, revisited the so-called out-of-Africa model and studied in forward simulations with discrete and not overlapping generations the effect of inbreeding on the average number of recessive lethals in the genome. We were able to reproduce in both frameworks the drop in the incidence of recessive disorders, which is a transient phenomenon during and after the growth phase of a population, and therefore showed their equivalence. With the simulation frameworks, we also provide the means to study and visualize the effect of different kin sizes and mating schemes on these parameters for educational purposes., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)