Monogenic forms of hypertension

Area of Science:

• Pediatric Nephrology
• Clinical Genetics
• Endocrinology

Background:

• Childhood arterial hypertension is less common than in adults but often secondary to underlying conditions.
• Some pediatric hypertension cases remain unexplained after excluding common causes, suggesting genetic origins.
• Single gene mutations can cause familial hypertension, inherited in autosomal dominant or recessive patterns.

Purpose of the Study:

• To highlight the role of monogenic disorders in pediatric secondary hypertension.
• To outline the distinct mechanisms of inherited hypertension.
• To emphasize the importance of hormonal and genetic testing for diagnosis.

Main Methods:

• Review of monogenic hypertensive disorders and their pathogenic mechanisms.
• Correlation of electrolyte abnormalities (potassium, acid-base balance) and renin levels with specific genetic mutations.
• Discussion of diagnostic approaches including hormonal assays and genetic testing.

Main Results:

• Three primary mechanisms of monogenic hypertension identified: hyperactivity of renal sodium/chloride reabsorption, enzyme deficiencies in adrenal steroidogenesis, and excessive aldosterone synthesis.
• Specific examples provided: Liddle's syndrome, Gordon's syndrome, congenital adrenal hyperplasia, apparent mineralocorticoid excess (AME), and glucocorticoid remediable aldosteronism.
• Abnormal potassium levels and suppressed renin secretion suggest familial hypertension, but mild cases may lack these markers.

Conclusions:

• Monogenic disorders are an important, often overlooked, cause of secondary hypertension in children.
• Understanding the distinct molecular mechanisms aids in diagnosis and management.
• Integrated hormonal and genetic evaluation is essential for early and accurate diagnosis of hereditary hypertensive disorders.