Intra- and inter- familial phenotypic variability in patients with Marfan syndrome

Introduction: Marfan syndrome (MFS) is an autoso-mal dominant genetic disorder caused by mutations of the fibrillin-1 gene (FBN-1) – 15q21.1, with multisyste-mic implications, associated with cardiovascular, mus-culoskeletal, ocular, cutaneous, pulmonary, neurologi-cal abnormalities.
Objective: The present study aims to highlight the di-versity of intra- and inter-familial phenotypic expressi-on in patients with MFS.
Methods: A series of 31 cases of MFS patients were evaluated at the Center of Expertise for Rare Genetic Cardiovascular Diseases in IUBCV „Prof. Dr. C. C. Ili-escu“ by completing individualized sheets, making a detailed pedigree, as well as by paraclinical and gene-tic investigations. Inclusion criteria were patients dia-gnosed with MFS based on the revised Ghent criteria, as well as their first degree relatives detected by active screening. Subsequently, the phenotypic particularities manifested in each family were then analyzed. Genetic testing was performed in all patients using MLPA assay. Results: 23 MFS index cases (11 men – 47%) were eva-luated, with the subsequent detection of 8 affected rela-tives (2 males – 25%). The median age of the probands was 46±13.2 years and the one of the relatives found 36.8±10 years. Within the pedigrees performed, there were noted between 1 and maximum 7 relatives affec-ted in a family. There were 16 cases with no significant heredity for MFS, possibly de novo mutations. On the basis of the family screening, 7 cases of MFS were re-ported in first degree relatives, as well as 1 case in rela-tives of second degree. There were two families where the penetration of the disease was 100% in the 2nd ge-neration, but in the 3rd generation none of the chil-dren were affected. As far as the main disorders of the disease are concerned, 30 patients (96.7%) had cardiac manifestations (aortic aneurysm/dissection/MVP), 16 ocular abnormalities (51.6%) and 25 skeletal features (80.6%). As common intrafamilial manifestations, the aortic pathology (aortic aneurysm/dissection) was found in 9 families, and that of the mitral valve at 5 of them. Also within 5 families there was both aortic and mitral involvement, but varying degrees among various family members (depending on their age). There were no families where the manifestations were completely different among its members. In one family, isolated ocular manifestations have been encountered. Only 5 patients were detected with genetic mutations in the fibrillin gene.
Conclusions: Marfan disease is a complex nosologi-cal entity with severe manifestations at a young age, requiring a good understanding of the full diagnostic criteria. There is an important interfamiliar variability in the clinical picture of dominant manifestations, the most common being the ocular and aortic pathology, while within the same family the dominant manifes-tations are similar. Family screening is essential in the management of these patients, leading to an early di-agnosis of the affected organs in first degree relatives.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)
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