SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism.
While the majority of cases of primary aldosteronism (PA) are sporadic, four forms of autosomal-dominant inheritance have been described: familial hyperaldosteronism (FH) types I to IV. FH-I, also called glucocorticoid-remediable aldosteronism, is characterized by early and severe hypertension, usually before the age of 20 years. It is due to the formation of a chimeric gene between the adjacent CYP11B2 and CYP11B1 genes (coding for aldosterone synthase and 11β-hydroxylase, respectively). FH-I is often associated with family history of stroke before 40years of age. FH-II is clinically and biochemically indistinguishable from sporadic forms of PA and is only diagnosed on the basis of two or more affected family members. No causal genes have been identified so far and no genetic test is available. FH-III is characterized by severe and early-onset hypertension in children and young adults, resistant to treatment and associated with severe hypokalemia. Mild forms, resembling FH-II, have been described. FH-III is due to gain-of-function mutations in the KCNJ5 gene. Recently, a new autosomal-dominant form of familial PA, FH-IV, associated with mutations in the CACNA1H gene, was described in patients with hypertension and PA before the age of 10years. In rare cases, PA may be associated with complex neurologic disorder involving epileptic seizures and cerebral palsy (Primary Aldosteronism, Seizures, and Neurologic Abnormalities [PASNA]) due to de novo germline CACNA1D mutations.
INSERM, U970, Paris Cardiovascular Research Center-PARCC, 56, rue Leblanc, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de génétique, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, Paris, France. Electronic address: maria-christina.zennaro@inserm.fr.
Maria-Christina
MC
Zennaro
INSERM, U970, Paris Cardiovascular Research Center-PARCC, 56, rue Leblanc, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de génétique, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, Paris, France.
Xavier
X
Jeunemaitre
D000328:Adult; D020747:Calcium Channels, T-Type / Q000235:genetics; D002648:Child; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005602:France; D005820:Genetic Testing; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics*; D006973:Hypertension / Q000235:genetics; D007008:Hypokalemia / Q000235:genetics; D009154:Mutation; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D020521:Stroke / Q000235:genetics; D055815:Young Adult
C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase
Calcium channel; Canal calcique; Canal potassique; Familial hyperaldosteronism; Glucocorticoid-remediable hyperaldosteronism; Hyperaldostéronisme familial; Hyperaldostéronisme suppressible par les glucocorticoïdes; Phenotypic variability; Potassium channel; Variabilité phénotypique