Genotype-phenotype spectrum and prognosis of early-onset Marfan syndrome.

BACKGROUND: Marfan syndrome is a genetic connective tissue disorder affecting skeletal, ocular, and cardiovascular organ systems. Previous research found that pathogenic variants clustered in exons 24-32 of fibrillin-1 (FBN1) gene result in more severe clinical phenotypes. Furthermore, genotype-phenotype correlation studies suggested that more severe cardiovascular phenotypes were related to variants held responsible for haploinsufficiency. Our objective was to analyze the differences in clinical manifestations and genotypes of individuals with early-onset Marfan syndrome and to assess their impact on management strategies. METHODS: We analyzed clinical and genetic data of a new patient with early-onset Marfan syndrome together with 51 previously reported ones in the PubMed database between 1991 and 2022. RESULTS: Analysis showed 94% (49/52) of pathogenic variants clustered in exons 24-32 of the FBN1. The most common skeletal features were arachnodactyly (98%), reduced elbow extension (48%), pectus deformity (40%), and scoliosis (39%). Haploinsufficiency variants were reported as having poor outcome in 87.5% of the cases. Among patients carrying variants that substitute a cysteine for another amino acid and those that do not change cysteine content, cardiac intervention was found to be associated with a better outcome (p = 0.035 vs. p = 0.002). Variants that create an extra cysteine residue were found to be associated with a higher risk of ectopia lentis. Additionally, children up to 36-months-old were more often reported as still alive at the time of publication compared to newborns (p < 0.01). CONCLUSIONS: Our findings have implications for prognosis, because different genotype groups and their resulting phenotype may require personalized care and management.

Bioarchaeological Notes on the Commingled Human Remains Held in the Church of Saint Francis of Paola, Sant'Angelo di Brolo, Sicily, Italy.

In this study, we examine human skeletal remains from the church of Saint Francis of Paola located in the small town of Sant'Angelo di Brolo, in the Italian region of Sicily. The preserved skeletal remains were temporarily transferred from their permanent resting place in the crypt for a macroscopic examination and evaluation. Various established methods were used to estimate age at death, sex, stature, any evidence of disease(s) as well as the fact that there was a minimum of 15 individuals. The findings were then subdivided into different groups of pathologies and recorded as individual cases. Amongst which, dental issues and cases of trauma were most prevalent. Additional conditions such as joint disease, congenital, metabolic and multifactorial disorders were also identified. The prevalence of dental decay indicates that the group's diet consisted largely of carbohydrates, and that their oral hygiene was poor. Furthermore, evidence of trauma and poor healing suggested that the town was isolated from the main medical centres of the island. Severe complications of traumas linked with a loss of movement and overall independence, as well as physical pain, must have had a significant impact on the lives of those affected.