When the standard diagnosis is not enough: Late-Onset Noonan Syndrome in a Patient with Hypertension and Cardiomyopathy

Left ventricular hypertrophy (LVH) requires careful differential diagnosis between acquired conditions and genetic forms, including sarcomeric cardiomyopathies and phenocopies. An asymptomatic 46-year-old woman presented with hypertensive crisis and marked LVH initially attributed to hypertension. A more detailed clinical examination, advanced imaging, and multidisciplinary assessment raised suspicion for a syndromic aetiology. Genetic testing identified a variant in the *LZTR1* gene, leading to a diagnosis of Noonan syndrome. Cascade family screening revealed the same variant in both children, who exhibited mild clinical signs, and not in the parents, who had negative phenotypes, confirming it as a de novo variant. This case illustrates a rare adult-onset presentation of Noonan syndrome, a RASopathy known to be a phenocopy of hypertrophic cardiomyopathy. Subtle systemic features, advanced imaging and genetic testing were key in reaching the correct diagnosis. This case also raises the issue of gene–environment interplay and underscores the importance of cascade genetic testing for family screening. Learning objective This case aims to highlight the importance of a comprehensive diagnostic approach to left ventricular hypertrophy, particularly when the degree of hypertrophy appears disproportionate to hypertension. Clinicians should recognize red flags suggestive of phenocopies, including systemic and dysmorphic features. The report underscores the role of multimodality imaging, detailed phenotypic assessment, and genetic testing in identifying RASopathies such as Noonan syndrome, even in adulthood, with important implications for management, prognosis, and family screening.