CASE REPORT article
Front. Cardiovasc. Med.
Sec. Cardiovascular Genetics and Systems Medicine
Severe cardiac valvular calcification in two Chinese brothers with Mandibuloacral dysplasia type A: A Case Report
Provisionally accepted
- Yunnan Fuwai Cardiovascular Hospital, Kunming, China
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Mandibuloacral dysplasia type A (MADA) is a rare progeroid syndrome associated with mutations in the Lamin A/C (LMNA) gene, primarily affecting skeletal, cutaneous, and adipose tissues. While certain LMNA gene mutations are known to cause cardiomyopathy and conduction system disease, severe early-onset calcific valvular heart disease is not conventionally considered a typical feature of MADA. This report describes two brothers from a consanguineous Han Chinese family who presented with classical MADA phenotypes alongside severe, early-onset cardiac valvular calcification. Genetic investigation revealed that both affected brothers carried a homozygous missense mutation, c.785A>G (p.Glu262Gly), in the LMNA gene. The elder brother, aged 41, successfully underwent transcatheter aortic valve implantation (TAVI) due to severe aortic valve stenosis. This finding represents the first association, to our knowledge, between the homozygous LMNA c.785A>G (p.Glu262Gly) mutation and significant severe early-onset cardiac valvular calcification manifesting as a prominent feature within the MADA phenotype, thus expanding the clinical spectrum associated with MADA and this specific LMNA variant. This case highlights a potentially underrecognized cardiovascular manifestation in MADA patients and underscores the importance of comprehensive cardiac assessment in affected individuals, particularly those from consanguineous families.
Keywords: Cardiac valvular calcification, progeroid syndromes, aortic stenosis, Transcatheter aortic valve implantation (TAVI), laminopathies
Received: 02 Jul 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Guo, Zhang, Meng, Guo and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoqi Wang, yiguo003@ynpfph.org
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