RESUMEN
INTRODUCTION: Pseudoxanthoma Elasticum (PXE) is a rare autosomal recessive disorder originated by disease-causing variants in ABCC6 gene. The purpose of this study was to characterize the genetic landscape, phenotypic spectrum and genotype-phenotype correlations in a Portuguese cohort of PXE patients. METHODS: Multicentric cross-sectional study conducted in patients with a clinical and genetic diagnosis of PXE. Patients were identified using the IRD-PT registry (www.retina.com.pt). Genotypes were classified into 3 groups: (1) two truncating variants, (2) two non-truncating variants, or (3) mixed variants. Deep phenotyping comprised a comprehensive ophthalmologic and systemic evaluation using the updated Phenodex Score (PS). RESULTS: Twenty-seven patients (23 families) were included. Sixteen different ABCC6 variants were identified, 7 of which are novel. The most prevalent variant was the nonsense variant c.3421C > T p.(Arg1141*) with an allele frequency of 18.5%. All patients exhibited ocular manifestations. Cutaneous manifestations were present in most patients (88.9%, n = 24/27). A PS score > E2 was strongly associated with worse visual acuity (B = -29.02; p = 0.001). No association was found between genotypic groups and cutaneous, vascular or cardiac manifestations. CONCLUSIONS: This study describes the genetic spectrum of patients with PXE for the first time in a Portuguese cohort. A total of 16 different variants in ABCC6 were found (7 of which are novel), thus highlighting the genotypic heterogeneity associated with this condition and expanding its mutational spectrum. Still, no major genotype-phenotype associations could be established.
RESUMEN
Aortic coarctation is a common congenital heart defect that often requires correction at a young age. Currently, success is defined by the achievement of a durable repair with low morbidity and mortality. We sought to systematically review the literature on risk factors for recoarctation and mortality in infants submitted to aortic arch coarctation repair under 1 year of age. PubMed and Scopus were searched for studies reporting risk factors for recoarctation and mortality from January 1989 to August 2019. Among the 1038 retrieved articles, 18 met the inclusion criteria, with a total of 2891 patients. The extracted risk factors for recoarctation were comprehensively summarized in the following categories: demographic variables, associated anomalies, clinical and repair variables, and morphometric variables. Younger age and lower weight were weak determinants of need for reintervention, while smaller aortic arch was a strong predictor of recoarctation. While balloon angioplasty is a clear risk factor for arch restenosis, the chosen surgical technique is not a strong risk factor. Associated minor cardiac anomalies and lower weight at surgery were important risk factors for death. Younger and smaller infants are at increased risk for adverse outcomes when submitted to aortic arch coarctation repair. This is particularly important when associated with smaller arch morphology. Strategies to improve the management of these patients may play a key role in improving their outcomes. Notably, surgical technique was not a strong predictor of recoarctation and mortality, suggesting that the choice of one over the other should be tailored.
