Table 1.
Hypertension (HTN)-related monogenic syndromes.
| Monogenic Syndrome | Inheritance | Gene | Locus | Phenotype | Therapeutic Indications |
|---|---|---|---|---|---|
| Pheochromocytomas/Paragangliomas | Autosomal dominant |
SDHA
SDHB SDHC SDHD SDHAF2 TMEM127 MAX |
5p15.3 1p36.13 1q23.3 11q23.1 11q12.2 2q11.2 14q23.3 |
Paragangliomas or pheochromocytomas. | Surgery/α adrenergic blockers |
| von Hippel–Lindau syndrome | Autosomal dominant | VHL | 3p25.3 | Retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma, pheochromocytomas, pancreatic tumours. | Surgery/α adrenergic blockers (for pheochromocytoma) |
| Multiple endocrine neoplasia, type 2A | Autosomal dominant | RET | 10q11.2 | Medullary thyroid carcinoma, parathyroid adenomas, pheochromocytoma. | Surgery/α adrenergic blockers (for pheochromocytoma) |
| Neurofibromatosis type 1 | Autosomal dominant | NF1 | 17q11.2 | Skin pigmentation, skin neurofibromas and brain tumours. Pheochromocytoma. | Surgery/α adrenergic blockers (for pheochromocytoma) |
| GRA–familial hyperaldosteronism type 1 | Autosomal dominant | CYP11B1 CYP11B2 | 8q24.3 | Familial form of PA | Glucocorticoids |
| Familial hyperaldosteronism type 2 | Autosomal dominant | N.A. | 7p22.3-7p22.1 | Familial form of PA | Mineralocorticoid receptor antagonist/unilateral adrenalectomy (for APA) |
| Familial hyperaldosteronism type 3 | Autosomal dominant | KCNJ5 | 8q24.3 | Severe form of PA with bilateral adrenal hyperplasia | Bilateral adrenalectomy in drug-resistant patients |
| Familial hyperaldosteronism type 4 | Autosomal dominant | CACNA1H | 16p13.3 | Familial form of PA | Mineralocorticoid receptor antagonist |
| PASNA syndrome | N.A. | CACNA1D | 3p21.3 | PA and complex neurological disorders (seizures and functional neurological abnormalities, resembling cerebral palsy). | N.A. |
| Sporadic APA | N.A. |
KCNJ5
ATP1A1 ATP2B3 CACNA1D |
11q24.3 1p31.1 Xq28 3p21.3 |
Sporadic forms of PA. | Adrenalectomy |
| Pseudohypoaldosteronism, type 2 (Gordon’s syndrome) | Autosomal dominant (*dominant/recessive) |
WNK1
WNK4 CUL3 KLHL3 * |
12p12.3 17q21.2 2q36.2 5q31.2 |
HyperK+ hyperCl− metabolic acidosis. Low PRA and low-normal AC. | Thiazide diuretics |
| Apparent mineralocorticoid excess (AME) Syndrome | Autosomal recessive | HSD11B2 | 16q22.1 | Hypokalemia. Low PRA and AC. Increased cortisol/cortisone ratio. | Mineralocorticoid receptor antagonist |
| Liddle’s syndrome | Autosomal dominant | SCNN1B, SCNN1G | 16p12.2 | ENaC constitutive activation. Hypokalemia. Low PRA and AC. | ENaC blockers (amiloride, triamterene) |
| 11β-hydroxylase deficiency | Autosomal recessive | CYP11B1 | 8q24.3 | Virilisation, short stature. Low PRA and AC. HypoK+ alkalosis. |
Glucocorticoids to inhibit ACTH-driven adrenal hyperpasia |
| 17α-hydroxylase deficiency | Autosomal recessive | CYP17A1 | 10q24.3 | HypoK+ alkalosis. Absent sexual maturation. Androgen deficiency. | Glucocorticoids to inhibit ACTH-driven adrenal hyperpasia |
| Hypertension with brachydactyly Type E | Autosomal dominant | PDE3A | 12p12.3 12p12.1 |
Brachydactyly, short phalanges and metacarpals. | N.A. |
| Hypertension exacerbated by pregnancy | Autosomal dominant | NR3C2 | 4q31.23 | Early onset hypertension exacerbated during pregnancy. | N.A. |
GRA, glucocorticoid remediable aldosteronism. PA, primary aldosteronism. N.A., not available. PASNA, primary aldosteronism, seizures and neurologic abnormalities. APA, aldosterone producing adenoma. HyperK+, hyperkalemic. HyperCl−, hyperchloraemic. PRA, plasma renin activity. AC, aldosterone concentration. HypoK+, hypokalemic. ENaC, epithelial sodium channel. Modified from Padmanabhan et al. [7].