Advanced Cardiovascular Disease in Marbach-Rustad Progeroid Syndrome (LEMD2 p.Ser479Phe)
Related Experiment Video
Updated: Nov 3, 2026

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
Tacianne R B Delamain1, Giseli Casarini1, José H H Delamain1
1Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
Background:
Marbach-Rustad progeroid syndrome results from the recurrent heterozygous LEMD2 c.1436C>T (p.Ser479Phe) variant. Four cases have been reported, with cardiac involvement absent or only qualitatively described.
Case Summary:
A 30-year-old man with short stature, skeletal fragility, and facial dysmorphism presented with syncope from high-grade atrioventricular block. Echocardiography showed premature severe calcific aortic stenosis and mild mitral stenosis. Cardiac magnetic resonance showed preserved biventricular function with no late gadolinium enhancement; computed tomography confirmed valvular calcification but no coronary calcium. Chagas serology was negative. Whole-genome sequencing confirmed the p.Ser479Phe variant. He received a permanent pacemaker and, 6 months later, transcatheter aortic valve replacement. Evaluation also revealed overt type 2 diabetes, severe hypertriglyceridemia, and nephropathy: the most advanced metabolic phenotype reported.
Discussion:
This case shows that the p.Ser479Phe variant can cause advanced, intervention-requiring cardiovascular disease (objectively quantified and, to our knowledge, the first in vivo characterization by cardiac magnetic resonance). These findings support routine cardiac and metabolic surveillance in LEMD2-associated progeroid syndromes.
More Related Videos
Related Concept Videos
Rheumatic Heart Disease I: Introduction
Huntington Disease l: Introduction
Lysosomal Hydrolases
Rheumatic Heart Disease II: Clinical Manifestations and Diagnostic Studies
Cardiomyopathy II: Dilated Cardiomyopathy
Cardiomyopathy III: Hypertrophic Cardiomyopathy

