European Journal of Pediatrics

, Volume 171, Issue 10, pp 1433–1439 | Cite as

Monogenic forms of hypertension

  • Giacomo Domenico Simonetti
  • Markus G. Mohaupt
  • Mario G. Bianchetti


Arterial hypertension in childhood is less frequent as compared to adulthood but is more likely to be secondary to an underlying disorder. After ruling out more obvious causes, some patients still present with strongly suspected secondary hypertension of yet unknown etiology. A number of these children have hypertension due to single gene mutations inherited in an autosomal dominant or recessive fashion. The finding of abnormal potassium levels (low or high) in the presence of suppressed renin secretion, and metabolic alkalosis or acidosis should prompt consideration of these familial diseases. However, mild hypertension and the absence of electrolyte abnormalities do not exclude hereditary conditions. In monogenic hypertensive disorders, three distinct mechanisms leading to the common final pathway of increased sodium reabsorption, volume expansion, and low plasma renin activity are documented. The first mechanism relates to gain-of-function mutations with a subsequent hyperactivity of renal sodium and chloride reabsorption leading to plasma volume expansion (e.g., Liddle's syndrome, Gordon's syndrome). The second mechanism involves deficiencies of enzymes that regulate adrenal steroid hormone synthesis and deactivation (e.g., subtypes of congenital adrenal hyperplasia, apparent mineralocorticoid excess (AME)). The third mechanism is characterized by excessive aldosterone synthesis that escapes normal regulatory mechanisms and leading to volume-dependent hypertension in the presence of suppressed renin release (glucocorticoid remediable aldosteronism). Hormonal studies coupled with genetic testing can help in the early diagnosis of these disorders.


Aldosterone Arterial hypertension Childhood Children Genetics Renin Steroid profile Mineralocorticoid-like activity 


Conflict of interest

The author declares that he has no conflict of interest and no financial relationships that might have influenced the present work.


  1. 1.
    Dave-Sharma S, Wilson RC, Harbison MD et al (1998) Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab 83:2244–2254PubMedCrossRefGoogle Scholar
  2. 2.
    Dluhy RG, Lifton RP (1995) Glucocorticoid-remediable aldosteronism (GRA): diagnosis, variability of phenotype and regulation of potassium homeostasis. Steroids 60:48–51PubMedCrossRefGoogle Scholar
  3. 3.
    Ferrari P, Lovati E, Frey FJ (2000) The role of the 11beta-hydroxysteroid dehydrogenase type 2 in human hypertension. J Hypertens 18:241–248PubMedCrossRefGoogle Scholar
  4. 4.
    Findling JW, Raff H, Hansson JH et al (1997) Liddle's syndrome: prospective genetic screening and suppressed aldosterone secretion in an extended kindred. J Clin Endocrinol Metab 82:1071–1074PubMedCrossRefGoogle Scholar
  5. 5.
    Gordon RD (1986) Syndrome of hypertension and hyperkalemia with normal glomerular filtration rate. Hypertension 8:93–102PubMedCrossRefGoogle Scholar
  6. 6.
    Gordon RD, Geddes RA, Pawsey CG et al (1970) Hypertension and severe hyperkalaemia associated with suppression of renin and aldosterone and completely reversed by dietary sodium restriction. Australas Ann Med 19:287–294PubMedGoogle Scholar
  7. 7.
    Guyton AC, Coleman TG, Cowley AV Jr et al (1972) Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med 52:584–594PubMedCrossRefGoogle Scholar
  8. 8.
    Lifton RP, Dluhy RG, Powers M et al (1992) A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 355:262–265PubMedCrossRefGoogle Scholar
  9. 9.
    Litchfield WR, Anderson BF, Weiss RJ et al (1998) Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension 31:445–450PubMedCrossRefGoogle Scholar
  10. 10.
    Lurbe E, Cifkova R, Cruickshank JK et al (2009) Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens 27:1719–1742PubMedCrossRefGoogle Scholar
  11. 11.
    Martinez-Aguayo A, Aglony M, Campino C et al (2010) Aldosterone, plasma renin activity, and aldosterone/renin ratio in a normotensive healthy pediatric population. Hypertension 56:391–396PubMedCrossRefGoogle Scholar
  12. 12.
    Milford DV (1999) Investigation of hypertension and the recognition of monogenic hypertension. Arch Dis Child 81:452–455PubMedCrossRefGoogle Scholar
  13. 13.
    Morineau G, Sulmont V, Salomon R et al (2006) Apparent mineralocorticoid excess: report of six new cases and extensive personal experience. J Am Soc Nephrol 17:3176–3184PubMedCrossRefGoogle Scholar
  14. 14.
    National high blood pressure education program working group on high blood pressure in children and adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRefGoogle Scholar
  15. 15.
    Nunez BS, Rogerson FM, Mune T et al (1999) Mutants of 11beta-hydroxysteroid dehydrogenase (11-hsd2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess. Hypertension 34:638–642PubMedCrossRefGoogle Scholar
  16. 16.
    Rodriguez-Soriano J, Vallo A (1988) Renal tubular hyperkalaemia in childhood. Pediatr Nephrol (Berlin, Germany) 2:498–509CrossRefGoogle Scholar
  17. 17.
    Shimkets RA, Warnock DG, Bositis CM et al (1994) Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell 79:407–414PubMedCrossRefGoogle Scholar
  18. 18.
    Spitzer A, Edelmann CM Jr, Goldberg LD et al (1973) Short stature, hyperkalemia and acidosis: a defect in renal transport of potassium. Kidney Int 3:251–257PubMedCrossRefGoogle Scholar
  19. 19.
    Stowasser M, Bachmann AW, Huggard PR et al (2000) Treatment of familial hyperaldosteronism type I: only partial suppression of adrenocorticotropin required to correct hypertension. J Clin Endocrinol Metab 85:3313–3318PubMedCrossRefGoogle Scholar
  20. 20.
    Vehaskari VM (2009) Heritable forms of hypertension. Pediatr Nephrol (Berlin, Germany) 24:1929–1937CrossRefGoogle Scholar
  21. 21.
    Wilson RC, Krozowski ZS, Li K et al (1995) A mutation in the hsd11b2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab 80:2263–2266PubMedCrossRefGoogle Scholar
  22. 22.
    Yang CL, Angell J, Mitchell R et al (2003) Wnk kinases regulate thiazide-sensitive Na-Cl cotransport. J Clin Investig 111:1039–1045PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Giacomo Domenico Simonetti
    • 1
  • Markus G. Mohaupt
    • 2
  • Mario G. Bianchetti
    • 3
  1. 1.Division of Pediatric Nephrology, Children’s HospitalUniversity of BernBerneSwitzerland
  2. 2.Department of Nephrology and Hypertension, InselspitalUniversity of BernBernSwitzerland
  3. 3.Department of PediatricsOspedale Regionale Bellinzona and University of BernBernSwitzerland

Personalised recommendations