IllnessHyperaldosteronism, familial; differential diagnosis

NGS +

[Sanger]

Familial hyperaldosteronism is a group of inherited diseases in which the adrenal glands produce excessive aldosterone causing renal salt retention and hypertension. The latter is often severe at a young age, sometimes with strokes, heart attacks and kidney failure. Familial hyperaldosteronism is classified into different types according to clinical features and genetic causes. In type I, hypertension begins in childhood or early adulthood and can range from mild to severe, but can be treated with glucocorticoids. Type I is usually caused by the fusion of the CYP11B1 and CYP11B2 genes. The CYP11B1 gene codes for cortisol and corticosterone, while aldosterone is produced via the CYP11B2 gene. When CYP11B1 and CYP11B2 are fused, too much aldosterone synthase and aldosterone is synthesized leading to hyperaldosteronism type I. In type II, caused by CLCN2 gene mutations, hypertension usually occurs in early to middle adulthood but is unaffected by glucocorticoids. In type III due to KCNJ5 mutations, the adrenal glands are grossly enlarged with severe childhood hypertension with frequent heart and kidney disease in consequence. Type IV results from mutations in the CACNA1H gene. A more complex syndromic type V includes primary aldosteronism with seizures and neurologic abnormalities due to mutations in the CACNA1D gene. Familial hyperaldosteronism is inherited in an autosomal dominant manner. Other forms of hyperaldosteronism are not transmitted in families, but they are caused e.g. by somatic driver mutations in various genes. The diagnostic yield in familial hyperaldosteronism is incomplete, and hence a negative DNA test result cannot exclude the clinical diagnosis.

Reference: https://www.nature.com/articles/s12276-019-0337-9

• Alias: Familial hyperaldosteronism [Conn syndrome]
• Allelic: Epilepsy, childhood absence, susceptibility to, 6 (CACNA1H)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 11 (CLCN2)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 6 (CACNA1H)
• Allelic: Epilepsy, juvenile absence, susceptibility to, 2 (CLCN2)
• Allelic: Epilepsy, juvenile myoclonic, susceptibility to, 8 (CLCN2)
• Allelic: Hypoaldosteronism, congenital, due to CMO I deficiency (CYP11B2)
• Allelic: Hypoaldosteronism, congenital, due to CMO II deficiency (CYP11B2)
• Allelic: Leukoencephalopathy with ataxia (CLCN2)
• Allelic: Long QT syndrome 13 (KCNJ5)
• Allelic: Low renin hypertension, susceptibility to (CYP11B2)
• Allelic: Sinoatrial node dysfunction and deafness (CACNA1D)
• Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (CYP11B1)
• Aldosterone to renin ratio raised (CYP11B2)
• Aldosteronism, glucocorticoid-remediable (CYP11B1)
• Hyperaldosteronism, familial, type I (CYP11B1)
• Hyperaldosteronism, familial, type II (CLCN2)
• Hyperaldosteronism, familial, type III (KCNJ5)
• Hyperaldosteronism, familial, type IV (CACNA1H)
• Primary hyperaldosteronism-seizures-neurological abnormalities; type V (CACNA1D)