Analysis of variability of clinical manifestations in children with Marfan syndrome

Abstract

Marfan syndrome is often found in clinical practice, first of all, by pediatricians, cardiologists, orthopedists, ophthalmologists. The disease is caused by heterozygous mutations of the FBN1 gene. This gene encodes the fibrillin-1 glycoprotein, which is a component of elastic microfibrils of connective tissue. Based on the examination of adult patients with Marfan syndrome, it was suggested that the variability of the clinical symptoms is apparently largely due to the nucleotide variants of the FBN1 gene.Purpose. Comparative analysis of clinical and genetic data of a group of children with molecularly and genetically confirmed Marfan syndrome.Results. Examination of 55 children showed that the clinical picture of Marfan syndrome is characterized by various symptom complexes. The most severe form of the disease with the presence of a triad of cardinal signs (aortic dilatation, ectopia lentis, skeletal disorders) was diagnosed in less than 1/3 of cases. In more than 2/3 of patients, individual cardinal manifestations were absent, making the symptom complex incomplete. According to the molecular genetic results, the patients were divided into 2 groups: 31 children had FBN1 gene mutations leading to haploinsufficiency, or loss-of-function (LoF) mutations; 24 children had FBN1 gene mutations with a dominant negative effect. Comparison of clinical and genetic data of patients of these two groups showed that LoF mutations were significantly (p<0.05) associated with the indicator of involvement in the pathological process of connective tissue, with an earlier manifestation of pathology of the visual organ and at the same time with the absence of ectopia lentis.Conclusion. Further analysis of clinical and genetic relationships is required to develop criteria for predicting the course of Marfan syndrome and substantiating medical observation of patients.