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Case Report: Discordant hypertrophic cardiomyopathy in monozygotic twins with LEOPARD syndrome and an identical PTPN11 c.1391G > C (p.Gly464Ala) mutation

Year: 2026

Type: article

Abstract: LEOPARD syndrome (LS; Noonan syndrome with multiple lentigines) is a rare autosomal dominant RASopathy in which PTPN11 mutations cause hypertrophic cardiomyopathy (HCM) with highly variable expressivity. We report adolescent monozygotic twin brothers carrying an identical PTPN11 c.1391G > C (p.Gly464Ala) mutation that arose de novo , who developed discordant cardiac phenotypes despite sharing a genome and an intrauterine and postnatal environment. The younger twin developed obstructive HCM with systolic anterior motion of the mitral valve and left ventricular outflow tract obstruction (peak resting gradient 36 mmHg, peak Valsalva gradient 61 mmHg), together with pectus excavatum and macroglossia; the older twin had non-obstructive HCM (maximal septal thickness 12 mm) with a patent foramen ovale. Both twins had multiple lentigines, facial dysmorphism, and sensorineural hearing loss requiring cochlear implantation. The younger twin was treated with a beta-blocker and activity restriction, whereas the older twin was managed with surveillance alone. This case demonstrates that an identical RASopathy mutation can produce divergent forms of HCM, supports a role for non-genetic modifiers in cardiovascular expression, and underscores the need for hemodynamics-guided, individualized cardiovascular management in LS.

Source: Frontiers in Cardiovascular Medicine

DOI: 10.3389/fcvm.2026.1978684

Authors: Xin Xue, Yayuan Ning, Fang Yao, Xiaowei Zhang, Xianjing Song

Institutions: Jilin University, Second Affiliated Hospital of Jilin University

Language: English

Topic: Cardiomyopathy and Myosin Studies

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801