Primary Aldosteronism, Seizures, And Neurologic Abnormalities

A number sign (#) is used with this entry because of evidence that primary aldosteronism with seizures and neurologic abnormalities (PASNA) is caused by heterozygous mutation in the CACNA1D gene (114206) on chromosome 3p21.

Clinical Features

Scholl et al. (2013) studied 2 patients with primary aldosteronism and neurologic abnormalities. The first patient was a 3-year-old girl of European ancestry who was diagnosed at birth with hypertension as well as biventricular hypertrophy, ventricular septal defect, pulmonary hypertension, and second-degree atrioventricular block. Her aldosterone levels were high, with low plasma renin activity (PRA) and an elevated aldosterone/renin ratio, consistent with primary hyperaldosteronism. Her clinical course was notable for uncontrolled hypertension with hypokalemia. Other features included generalized tonic-clonic seizures beginning at 7 months of age, during the evaluation of which she was noted to have cortical blindness, spasticity, and cerebral palsy. At 12 months of age, the frequency of seizures, which included myoclonic, complex partial, and tonic-clonic seizures, increased to more than once a month. At age 2 years, she spontaneously passed a renal stone. At age 3 years, she was not ambulatory or verbal (global developmental delay). The second patient was a 10-year-old African American girl who was born by cesarean section after uterine rupture and required resuscitation; she was subsequently diagnosed with cerebral palsy, spastic quadriplegia, mild athetosis, severe generalized intellectual disability, and complex and partial generalized seizures. At age 5 years, she was markedly hypertensive with persistently elevated blood pressure and polydipsia, and she also had hypokalemia and metabolic alkalosis. Serum aldosterone levels were high despite suppressed PRA. CT scan showed no adrenal abnormality, and echocardiogram showed mild left ventricular hypertrophy. Neither patient had a family history of early-onset hypertension or seizures.

Molecular Genetics

Scholl et al. (2013) sequenced the candidate gene CACNA1D in 100 unrelated individuals with unexplained early-onset primary aldosteronism and identified 2 girls with de novo heterozygous gain-of-function missense mutations, G403D (114206.0002) and I770M (114206.0003). In addition to hypertension, both patients had seizures and neurologic abnormalities.