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Peer-reviewedCC BY 4.0Frontiers in Cardiovascular Medicine

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

  • Xin Xue1
  • Yayuan Ning1
  • Fang Yao1
  • Xiaowei Zhang1
  • Xianjing Song1
  1. 1Department of Cardiology, Second Hospital of Jilin University
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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.

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Cite

BibTeXRIS
BibTeX
@article{xue2026case,
  title = {{Case Report: Discordant hypertrophic cardiomyopathy in monozygotic twins with LEOPARD syndrome and an identical PTPN11 c.1391G > C (p.Gly464Ala) mutation}},
  author = {Xin Xue and Yayuan Ning and Fang Yao and Xiaowei Zhang and Xianjing Song},
  journal = {Frontiers in Cardiovascular Medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fcvm.2026.1978684},
  url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1978684/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Case Report: Discordant hypertrophic cardiomyopathy in monozygotic twins with LEOPARD syndrome and an identical PTPN11 c.1391G > C (p.Gly464Ala) mutation
AU  - Xin Xue
AU  - Yayuan Ning
AU  - Fang Yao
AU  - Xiaowei Zhang
AU  - Xianjing Song
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Cardiovascular Medicine
DO  - 10.3389/fcvm.2026.1978684
UR  - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1978684/full
AB  - 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.
SN  - 2297-055X
ER  -