RESUMEN
Marfan syndrome (MFS) is an autosomal dominant condition characterized by aortic aneurysm, skeletal abnormalities, and lens dislocation, and is caused by variants in the FBN1 gene. To explore causes of MFS and the prevalence of the disease in Iceland we collected information from all living individuals with a clinical diagnosis of MFS in Iceland (n = 32) and performed whole-genome sequencing of those who did not have a confirmed genetic diagnosis (27/32). Moreover, to assess a potential underdiagnosis of MFS in Iceland we attempted a genotype-based approach to identify individuals with MFS. We interrogated deCODE genetics' database of 35,712 whole-genome sequenced individuals to search for rare sequence variants in FBN1. Overall, we identified 15 pathogenic or likely pathogenic variants in FBN1 in 44 individuals, only 22 of whom were previously diagnosed with MFS. The most common of these variants, NM_000138.4:c.8038 C > T p.(Arg2680Cys), is present in a multi-generational pedigree, and was found to stem from a single forefather born around 1840. The p.(Arg2680Cys) variant associates with a form of MFS that seems to have an enrichment of abdominal aortic aneurysm, suggesting that this may be a particularly common feature of p.(Arg2680Cys)-associated MFS. Based on these combined genetic and clinical data, we show that MFS prevalence in Iceland could be as high as 1/6,600 in Iceland, compared to 1/10,000 based on clinical diagnosis alone, which indicates underdiagnosis of this actionable genetic disorder.
Asunto(s)
Síndrome de Marfan , Humanos , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/epidemiología , Síndrome de Marfan/genética , Islandia/epidemiología , Fibrilina-1/genética , Genotipo , Linaje , Mutación , Adipoquinas/genéticaRESUMEN
In recent months the incedence of invasive group A streptococcal infections (Streptococcus pyogenes) has increased worldwide. In the Children's Hospital Iceland 20 such cases were admitted during a four month period, until which time the avarage was one or two children admitted with an invasive GAS infection per year. To demonstrate the variability in the presentation of these invasive infections four cases were chosen for discussion in this case-series. Empyema with toxic shock syndrome, meningitis, orbital abscess and fascitis of the leg are reviewed.
