PASNA syndrome with overlapping CACNA1D and MED12L variants: expanding the spectrum

Hypertension in infancy is rare and usually secondary to renal, cardiovascular, or endocrine disorders. PASNA syndrome (primary aldosteronism, seizures, and neurological abnormalities) (OMIM #615474) caused by activating CACNA1D mutations, has been increasingly recognized with wider availability of genetic testing. We report a 5-month-old male infant with incidentally detected severe hypertension (>99th percentile), neonatal jitteriness, and global developmental delay. Laboratory evaluation showed markedly elevated aldosterone (824 ng/dL) (SI: 22.9 nmol/L) (reference range, 5-150 ng/dL [SI: 0.14-4.2 nmol/L]) with low-normal renin and normal renal and cardiac imaging. Genetic analysis revealed a heterozygous CACNA1D missense variant (c.2241C > G; p.Phe747Leu) likely pathogenic and a heterozygous MED12L variant, classified as variants of unknown significance. The mother was an asymptomatic carrier of the CACNA1D variant. Blood pressure improved with nifedipine followed by spironolactone (2.5 mg/kg/day). Neurological symptoms partially improved, though motor delay persisted. This case expands the phenotypic spectrum of PASNA syndrome and highlights the need for early genetic evaluation in infants with unexplained hypertension and neurological abnormalities. The concurrent MED12L variant may contribute to the neurodevelopmental phenotype, underscoring the complexity of dual-gene involvement.