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

TL;DR

A 36-year-old man with early-onset hypertension had a new genetic variant in CACNA1H, suggesting the need for genetic testing in similar cases.

Contribution

A novel CACNA1H variant is identified in a patient with early-onset hypertension, expanding understanding of monogenic hypertension.

Findings

A heterozygous CACNA1H variant (c.3988G > A, p.V1330I) was found in a patient with refractory hypertension and elevated aldosterone.

The variant shows autosomal dominant inheritance confirmed by Sanger sequencing and family analysis.

Genetic testing is recommended alongside biochemical markers for accurate diagnosis of monogenic hypertension.

Abstract

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.

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.

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.

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