aldosterone-producing adenoma with seizures and neurological abnormalities

Aldosterone-producing adenoma with seizures and neurological abnormalities is a very rare multisystem condition that combines endocrine dysfunction with significant developmental and neurological features. It arises from pathogenic variants in the CACNA1D gene, which encodes a calcium channel important for hormone secretion as well as brain and heart function. Symptoms usually appear in infancy or early childhood and affect individuals of any sex. Fewer than one in a million people are thought to be affected worldwide, and most known cases have been reported as single occurrences rather than through family clusters.

The clinical picture varies widely between individuals, but developmental and neurological concerns are often the first clues. All reported children have global developmental delay or intellectual disability, and many meet criteria for autism spectrum disorder. Seizures, including bilateral tonic–clonic and myoclonic episodes, are common and may appear in the first years of life. Muscle tone differences such as hypotonia, spasticity, or athetosis contribute to motor delays, and some children are described as having a cerebral palsy–like presentation. Cerebral visual impairment has also been noted. Endocrine and cardiovascular findings stem from excessive aldosterone production. Nearly all individuals have persistent hypertension, low blood potassium (hypokalemia), suppressed renin levels, and metabolic alkalosis. Some develop classic primary hyperaldosteronism and, in a subset, nephrolithiasis or congenital hyperinsulinemic hypoglycemia. Cardiac structural or functional changes such as ventricular septal defect, patent foramen ovale, left or biventricular hypertrophy, and second-degree atrioventricular block have been reported. Not every person experiences every feature, and severity ranges from mild endocrine abnormalities with manageable blood pressure to complex neurological impairment with refractory seizures. Additional challenges can include self-injurious behavior and distinctive facial features, underscoring the need for individualized care.

This condition is caused by disease-causing variants in CACNA1D, which encodes the alpha-1 subunit of an L-type voltage-gated calcium channel. Gain-of-function changes keep the channel open longer than usual, increasing calcium influx into cells. In the adrenal glands, this triggers excess aldosterone release, while in the brain and heart it disrupts normal electrical signaling and development. Aldosterone-producing adenoma with seizures and neurological abnormalities follows an autosomal dominant inheritance pattern, meaning one altered copy of CACNA1D can cause disease. However, most documented variants have arisen de novo, appearing for the first time in the affected child. When a variant is de novo the risk to siblings is usually low, though a person who carries the variant has a 50 percent chance of passing it to each child. Even within the same family the presentation can differ markedly, reflecting variable expressivity. Genetic counseling is recommended for families to discuss testing, recurrence risk, and family-planning options.

Currently, management focuses on supportive care and symptom control, coordinated through a multidisciplinary team. Antihypertensive medications and mineralocorticoid receptor antagonists are used to control blood pressure and correct hypokalemia. In selected cases, surgical removal of an adrenal adenoma may improve hormonal balance, but endocrine follow-up remains essential. Standard anti-seizure therapies are prescribed according to seizure type, and neurologists monitor for treatment response and side effects. Children benefit from early developmental interventions such as physical, occupational, and speech therapy, with individualized education plans to address cognitive and behavioral needs. Because this is a multi-system condition, regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Recommended monitoring typically includes periodic blood pressure and serum electrolyte checks, cardiac imaging, renal ultrasounds for kidney stones, and ongoing assessments of growth and developmental progress. Genetic counseling and psychological support for families round out comprehensive care.

Long-term outlook depends on the severity of endocrine and neurological involvement, and individual experiences with this condition differ significantly. Blood pressure and electrolyte abnormalities can often be controlled with medication or surgery, improving cardiovascular outcomes. Developmental and intellectual challenges usually persist into adulthood, but early intervention services can maximize functional skills and quality of life. Seizure control varies; some individuals achieve good management, while others need multiple medications. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling for ongoing guidance and family planning discussions.