Early-onset hypertension associated with a CACNA1H variant of uncertain significance: a case report and literature review

BACKGROUND: The prevalence of early-onset hypertension is rising annually and is accompanied by progressive target organ damage, contributing to a higher risk of cardiovascular mortality. In patients with early-onset hypertension characterized by refractory hypertension, elevated plasma aldosterone levels, and a family history of hypertension, monogenic hereditary hypertension, such as familial hyperaldosteronism, should be suspected, although this condition is rare. CASE PRESENTATION: A 36-year-old male patient with hypertension fails to achieve target blood pressure despite receiving four antihypertensive medications, including a diuretic. The patient exhibited elevated plasma aldosterone levels, while the aldosterone-to-renin ratio and serum potassium levels remain within normal ranges. Further genetic analysis identifies a heterozygous variant of uncertain significance in the CACNA1H gene (nucleotide change: c.3988G > A, amino acid change: p.V1330I, chromosomal location: chr16:1260601). This genetic variant has not been previously reported. The CACNA1H gene is associated with familial hyperaldosteronism type IV. Sanger sequencing validation and family pedigree analysis were performed, confirming an autosomal dominant inheritance pattern among family members. CONCLUSIONS: For patients with early-onset hypertension characterized by refractory hypertension, elevated plasma aldosterone levels, and a family history of hypertension, monogenic forms of hypertension, such as familial hyperaldosteronism, should be suspected. However, For patients with negative ARR but atypical clinical manifestations of elevated aldosterone levels, exclusive reliance on common biochemical markers, such as the aldosterone-to-renin ratio and serum potassium levels, may lead to misdiagnosis or underdiagnosis. Therefore, in addition to routine biochemical markers, genetic testing should be considered a complementary diagnostic tool for patients with early-onset hypertension and a family history of hypertension.