Key result
Novel CACNA1H and PPP2R5D variants linked to early-onset primary aldosteronism with intellectual disability.
Why the study?
Cases of early-onset hypertension with intellectual disability associated with concurrent CACNA1H and PPP2R5D mutations are rare and not well characterized.
Case Report (n=1)
No
Genetic forms of primary aldosteronism, such as CACNA1H mutations, should be considered and tested for in young patients presenting with atypical early-onset hypertension.
May prompt genetic testing in syndromic aldosteronism; leaves open digenic causality pending replication.
Mutations in the CACNA1H and PPP2R5D genes have been associated with functional abnormalities affecting both the endocrine and nervous systems. The CACNA1H gene encodes the T-type calcium channel CaV3.2, and pathogenic variants may alter channel activation and inactivation, resulting in increased intracellular calcium influx. Elevated intracellular calcium in adrenal zona glomerulosa cells acts as a key signal for aldosterone biosynthesis, thereby promoting excessive aldosterone secretion and contributing to the development of hypertension. The PPP2R5D gene encodes a regulatory subunit of protein phosphatase 2A (PP2A). Mutations in this gene may disrupt the regulatory function of PP2A, impairing the dephosphorylation of key neuroproteins and consequently affecting neural signal transduction and brain function. Cases of early-onset hypertension accompanied by intellectual disability associated with concurrent CACNA1H and PPP2R5D mutations remain rare. We report the case of an 18-year-old female presenting with early-onset hypertension and intellectual disability. Hypertension was first diagnosed at the age of 10 years and was accompanied by recurrent dizziness and headache. Physical examination revealed central obesity and signs of hyperandrogenism. Laboratory evaluation demonstrated elevated aldosterone levels with suppressed plasma renin activity, suggesting primary aldosteronism. Genetic analysis identified heterozygous variants in CACNA1H (c.6866C>T) and PPP2R5D (c.985A>G). Based on the clinical features and genetic findings, the patient was diagnosed with familial hyperaldosteronism type IV complicated by intellectual disability. This case highlights the importance of considering genetic forms of primary aldosteronism in young patients with early-onset hypertension and atypical clinical manifestations. Genetic testing may facilitate accurate diagnosis and guide individualized management.
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Zhang et al. (2026) conducted a case report in Primary aldosteronism with intellectual disability (n=1). CACNA1H and PPP2R5D mutations was evaluated on Clinical and genetic diagnosis. Concurrent heterozygous variants in CACNA1H and PPP2R5D were identified as the likely genetic cause of early-onset primary aldosteronism and intellectual disability in an 18-year-old female.
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