ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Familial hyperaldosteronism

Familial hyperaldosteronism
Literature review current through: Jan 2024.
This topic last updated: Jun 15, 2023.

INTRODUCTION — Familial hyperaldosteronism (FH) is an uncommon subset of primary aldosteronism. There are five forms of FH:

FH type I or glucocorticoid-remediable aldosteronism (GRA) due to a CYP11B1/CYP11B2 chimeric gene

FH type II caused by germline CLCN2 pathogenic variants

FH type III caused by germline KCNJ5 pathogenic variants

FH type IV caused by germline CACNA1H pathogenic variants

Primary aldosteronism with seizures and neurologic abnormalities (PASNA) caused by germline CACNA1D pathogenic variants

The five forms of FH will be reviewed here. Primary aldosteronism is discussed separately. (See "Diagnosis of primary aldosteronism" and "Pathophysiology and clinical features of primary aldosteronism" and "Treatment of primary aldosteronism".)

FAMILIAL HYPERALDOSTERONISM TYPE I (FH TYPE I) OR GLUCOCORTICOID-REMEDIABLE ALDOSTERONISM (GRA) — GRA was first described in a single family in 1966 [1]. Twenty-six years later the causative CYP11B1/CYP11B2 chimeric gene was discovered (figure 1) [2]. GRA is a form of hyperaldosteronism in which the hypersecretion of aldosterone can be reversed with physiologic doses of glucocorticoid [3-5].

It is rare, as illustrated by a study of 300 consecutive patients with primary aldosteronism; only two patients were diagnosed with GRA (prevalence = 0.66 percent) [6].

Pathophysiology — Normal subjects synthesize aldosterone in the zona glomerulosa (which lacks the 17-hydroxylase enzyme required for cortisol synthesis), but not in the corticotropin (ACTH)-sensitive zona fasciculata (which lacks the enzymes required to add the necessary aldehyde to corticosterone at the 18-carbon position). (See "Adrenal steroid biosynthesis".)

Patients with GRA, on the other hand, have ACTH-sensitive aldosterone production occurring in the zona fasciculata. Two isozymes of 11-beta-hydroxylase encoded by two genes on chromosome 8 are responsible for the biosynthesis of aldosterone and cortisol (figure 2):

The isozyme in the zona glomerulosa (CYP11B2, aldosterone synthase, P450as) catalyzes the conversion of deoxycorticosterone to corticosterone and of 18-hydroxycorticosterone to aldosterone.

The isozyme in the zona fasciculata (CYP11B1, P450c11) catalyzes the conversion of 11-deoxycortisol to cortisol and does not contribute to aldosterone synthesis.

The mutation in patients with GRA is fusion of the promoter region of the gene for CYP11B1 and the coding sequences of CYP11B2, resulting in ACTH-dependent activation of the aldosterone synthase effect on cortisol, corticosterone, and cortisol precursors (figure 1) [2,7]. As a result, these patients are biochemically unique in having markedly increased levels of 18-oxocortisol and 18-hydroxycortisol [2,3,7].

The zona fasciculata location of aldosterone synthesis is probably responsible for another interesting physiologic feature of GRA: Aldosterone release appears to be insensitive to the normally potent stimulus of potassium loading [8].

Clinical characteristics — GRA is inherited as an autosomal dominant trait, as a single copy of the abnormal gene is sufficient to cause the disease. The presence of this rare disorder as the cause of primary aldosteronism should be suspected from the positive family history and the typical onset of hypertension before age 21 years [3].

The plasma potassium concentration is normal in more than one-half of cases of GRA in contrast to the hypokalemia sometimes seen in primary aldosteronism due to an adrenal adenoma [3,8]. One possible explanation for this difference is that aldosterone release in GRA is primarily under the influence of ACTH; with the normal circadian rhythm of ACTH release, aldosterone secretion should be above normal for only part of the day. The lack of aldosterone response to dietary potassium mentioned above would also diminish net aldosterone release [8]. (See "Pathophysiology and clinical features of primary aldosteronism".)

The main clinical clues suggesting GRA in the normokalemic, hypertensive patient are the family history of hypertension, onset at a young age, and the frequent development of marked hypokalemia after the administration of a thiazide diuretic (which increases sodium delivery to the aldosterone-sensitive potassium secretory site in the cortical collecting tubule). The diagnostic approach to patients with the different forms of mineralocorticoid excess is reviewed elsewhere. (See "Pathophysiology and clinical features of primary aldosteronism" and "Diagnosis of primary aldosteronism".)

Intrafamily variability appears to occur with GRA, suggesting the presence of variations in the regulation of the altered gene and/or significant effects of modifier genes. This was shown in an affected family in which only one of three individuals with the chimeric gene had classic features of GRA, with the other two being normotensive, normokalemic, and having normal plasma renin activity and aldosterone levels [9].

Initial anecdotal observations of early cerebrovascular complications in patients with GRA have been confirmed in a review from the international registry for GRA [10]. Among patients with GRA, 18 percent had a cerebrovascular complication, 70 percent of which were hemorrhagic strokes due primarily to ruptured intracranial aneurysms. The case fatality rate was 61 percent and the mean age at the initial event was 32 years. In comparison, there were no strokes in GRA-negative family members.

The factors responsible for the increase in hemorrhagic stroke are uncertain, but it is likely that congenital hypertension during the early stages of cerebrovascular development plays a role. The possible presence of early cerebral hemorrhage in Liddle's syndrome, another form of congenital hypertension, is consistent with this hypothesis [11]. (See "Genetic disorders of the collecting tubule sodium channel: Liddle syndrome and pseudohypoaldosteronism type 1".)

The frequency of aneurysm rupture in GRA is somewhat higher than that reported in autosomal dominant polycystic kidney disease, another disorder in which hemorrhagic stroke can occur at a young age. It has been suggested that all patients with genetically proven GRA should undergo screening magnetic resonance (MR) angiography at puberty and every five years thereafter [10]. However, the benefit of such an approach has not been proven and must be weighed against the risk of prophylactic surgery for small aneurysms that might not rupture. This issue is discussed in detail elsewhere. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations".)

Diagnosis — The diagnosis of GRA is suspected on the basis of the clinical features described above. The plasma aldosterone is elevated and plasma renin activity is suppressed, but the aldosterone-renin ratio is typically not as high as with primary aldosteronism caused by an aldosterone-producing adenoma. (See "Diagnosis of primary aldosteronism".)

The diagnosis has, in the past, been established by dexamethasone suppression testing and demonstration of hypersecretion of 18-carbon oxidation products of cortisol: 18-hydroxycortisol and 18-oxocortisol [3]. However, we suggest that dexamethasone suppression testing be replaced by genetic testing, as described below.

Genetic testing using molecular biologic techniques to detect the chimeric gene is now preferred over dexamethasone suppression testing for making the diagnosis of GRA [12,13]. The value of this approach was illustrated in a study of 117 patients with primary aldosteronism, none of whom had the chimeric gene but six of whom (one with an adenoma and five with idiopathic hyperaldosteronism) had false-positive dexamethasone suppression tests [14].

The laboratories that provide clinical genetic testing can be found in the Genetic Testing Registry.

GRA is a rare subtype of primary aldosteronism, and the genetic screen should be performed on selected patients [15]. Indications include primary aldosteronism patients with onset at a young age (eg, <20 years), or a family history of primary aldosteronism or of strokes at a young age (eg, <40 years) [16].

In 2016, the Endocrine Society published an updated evidence-based guideline for the diagnosis and treatment of primary aldosteronism [17]. Our diagnostic and treatment approach to GRA outlined here is consistent with the guidelines.

Treatment — We suggest the exogenous administration of physiologic doses of a glucocorticoid (such as prednisone, dexamethasone, or hydrocortisone) as the first-line therapy. It will correct the overproduction of aldosterone by diminishing ACTH release and will usually lower the blood pressure toward or to normal and correct hypokalemia (if present) [4,18].

The smallest effective dose of an intermediate-acting glucocorticoid (eg, prednisone) should be administered at bedtime to suppress the early morning surge in ACTH. Target blood pressure in children should be guided by age-specific blood pressure percentiles. Children should be monitored by pediatricians with expertise in glucocorticoid therapy, with careful attention paid to preventing retardation of linear growth by overtreatment.

An alternative approach is treatment with mineralocorticoid receptor antagonists, which may be just as effective and avoids the potential disruption of the hypothalamic-pituitary-adrenal axis and risk of iatrogenic side effects [19]. In addition, glucocorticoid therapy or mineralocorticoid receptor blockade may even have a role in normotensive GRA patients.

FAMILIAL HYPERALDOSTERONISM TYPE II (FH TYPE II) — Familial hyperaldosteronism (FH) type II may be the most common form of FH. Like FH type I, FH type II is associated with hyperaldosteronism and autosomal dominant inheritance. Unlike FH type I, hyperaldosteronism in FH type II is not dexamethasone suppressible and is not associated with the hybrid gene mutation. FH type II is the familial occurrence of aldosterone-producing adenoma or bilateral idiopathic hyperplasia, or both, in the same kindred. Biochemically and morphologically, FH type II is indistinguishable from apparently nonfamilial primary aldosteronism.

In a study of 300 consecutive patients with primary aldosteronism, two patients were diagnosed with FH type I (prevalence = 0.66 percent) [6]. In the remaining 199 families who consented to be further investigated, 12 were diagnosed with FH type II (6 percent). The clinical and biochemical phenotypes of FH type II families were not different from sporadic primary aldosteronism patients [6]. Similar results were seen in a second series [20].

Pathogenic variants — In a recent report of a family with FH type II and 80 additional probands with unsolved early-onset primary aldosteronism, a germline CLCN2 chloride channel pathogenic variant was found in eight of the probands [21]. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa cells. All relatives with early-onset primary aldosteronism carried the CLCN2 pathogenic variant found in the proband. Pathogenic variants in the CLCN2 chloride channel may be responsible for all or some of the individuals who have been classified at FH type II [22]. Over time we may learn of a series of genes with pathogenic variants that contribute to what has been classified as FH type II.

Clinical features — FH type II is inherited as an autosomal dominant trait. The presence of FH type II should be suspected from the positive family history of hypertension. Intrafamily variability is common with some kindred members having primary aldosteronism due to aldosterone-producing adenomas and others due to bilateral idiopathic hyperplasia. Except for familial occurrence, there are no unique features or risks related to FH type II beyond those known for primary aldosteronism. (See "Diagnosis of primary aldosteronism" and "Pathophysiology and clinical features of primary aldosteronism" and "Treatment of primary aldosteronism".)

Approach to diagnosis — The laboratories that provide clinical genetic testing can be found in the Genetic Testing Registry. As highlighted in the 2016 Endocrine Society guidelines for the diagnosis and treatment of primary aldosteronism [17], all hypertensive first-degree relatives of patients with primary aldosteronism should undergo case-detection testing for primary aldosteronism with measurement of plasma aldosterone concentration and plasma renin activity. (See "Diagnosis of primary aldosteronism" and "Pathophysiology and clinical features of primary aldosteronism".)

Until more is learned about the genes with pathogenic variants that cause FH type II, the subtype evaluation of these patients should be identical to patients with apparent sporadic primary aldosteronism (algorithm 1) [23]. (See "Diagnosis of primary aldosteronism", section on 'Subtype classification'.)

Management — The treatment of patients with FH type II should be identical to patients with apparent sporadic primary aldosteronism. (See "Treatment of primary aldosteronism".)

FAMILIAL HYPERALDOSTERONISM TYPE III (FH TYPE III)

Mutations in KCNJ5 gene — Familial hyperaldosteronism (FH) type III was first described in a single family in 2008 [24]. This initial report included a father and two daughters who all presented with refractory hypertension before age seven years, and all three were treated with bilateral adrenalectomy. The adrenal glands showed massive hyperplasia [24]. Three years later, the causative germline pathogenic variant in this family was discovered: a pathogenic variant in and near the selectivity filter of the potassium channel KCNJ5 [25]. This KCNJ5 mutation produces increased sodium conductance and cell depolarization, triggering calcium entry into glomerulosa cells, the signal for aldosterone production and cell proliferation.

Thus far, 12 kindreds carrying six different germline KCNJ5 pathogenic variants have been identified: p.Thr158Ala, p.Gly151Glu, p.Gly151Arg, p. Ile157Ser, p.Tyr152Cys, and p.Glu145Gln [25-29]. The estimated prevalence of germline KCNJ5 pathogenic variants is 0.3 percent in patients with primary aldosteronism and 8 percent among patients with familial primary aldosteronism [26]. Most patients with germline KCNJ5 pathogenic variants present with polyuria, polydipsia, and refractory hypertension in childhood; investigations show marked hypokalemia and marked primary aldosteronism. In most cases, the degree of aldosterone hypersecretion is so marked that bilateral adrenalectomy is required. However, there is some heterogeneity in age at presentation (as old as 48 years) [30].

Since this initial report [25], other families with early-onset hyperaldosteronism have also been identified to have germline point mutations in the KCNJ5 gene [31,32]. In families in Europe with FH (glucocorticoid-remediable aldosteronism [GRA] excluded), a new germline G151E mutation was found in two primary aldosterone subjects from Italy and they presented a remarkably milder clinical and biochemical phenotype [26]. In four families with early-onset primary aldosteronism, germline G151R mutations were found in two with severe hyperplasia requiring surgery; two kindreds had G151E mutations and mild primary aldosteronism [27]. Surprisingly, G151E produced much larger sodium conductance than G151R, resulting in rapid sodium-dependent cell lethality; this may reduce primary aldosteronism and hyperplasia in vivo.

Clinical findings — FH type III is very rare and inherited as an autosomal dominant trait. The presence of FH type III should be suspected in children with primary aldosteronism and in patients with primary aldosteronism found to have massive adrenal hyperplasia.

Evaluation and diagnosis — Commercially available testing for germline KCNJ5 mutations is now available (https://www.ncbi.nlm.nih.gov/gtr/). This rare subtype of primary aldosteronism should be suspected in children with hyperaldosteronism and in families with more than one member with primary aldosteronism. (See "Diagnosis of primary aldosteronism" and "Pathophysiology and clinical features of primary aldosteronism".)

The subtype evaluation of patients with FH type III should be identical to patients with apparent sporadic primary aldosteronism (algorithm 1) [23]. (See "Diagnosis of primary aldosteronism", section on 'Subtype classification'.)

Adrenal computed tomography (CT) may show massive or milder bilateral hyperplasia. Adrenal venous sampling, if performed, would show bilateral aldosterone hypersecretion.

Therapy — The treatment of patients with FH type III should be identical to patients with apparent sporadic primary aldosteronism (algorithm 1) [23]. However, in selected cases of refractory disease associated with massive bilateral adrenal hyperplasia, bilateral laparoscopic adrenalectomy may need to be considered. (See "Treatment of primary aldosteronism".)

FAMILIAL HYPERALDOSTERONISM TYPE IV (FH TYPE IV)

Mutations in CACNA1H gene — An exome-sequencing study identified germline pathogenic variants in CACNA1H (encoding a T-type calcium channel) in five unrelated families with early-onset primary aldosteronism [33]. A subsequent study identified four additional unrelated patients with primary aldosteronism caused by germline pathogenic variants in CACNA1H, one of which had a multiplex developmental disorder [34].

Evaluation and diagnosis — Commercially available testing for germline CACNA1H pathogenic variants is now available (https://www.ncbi.nlm.nih.gov/gtr/). This rare subtype of primary aldosteronism should be suspected in children with hyperaldosteronism and in families with more than one member with primary aldosteronism. (See "Diagnosis of primary aldosteronism" and "Pathophysiology and clinical features of primary aldosteronism".)

The subtype evaluation of patients with FH type IV should be identical to patients with apparent sporadic primary aldosteronism (algorithm 1) [23]. (See "Diagnosis of primary aldosteronism", section on 'Subtype classification'.)

Adrenal computed tomography (CT) may show an apparent cortical adenoma, bilateral hyperplasia, or normal-appearing adrenal glands. Adrenal venous sampling, if performed, would show bilateral aldosterone hypersecretion.

Therapy — The treatment of patients with FH type IV should be identical to patients with apparent sporadic primary aldosteronism (algorithm 2) [23]. However, in selected cases of refractory disease associated with massive bilateral adrenal hyperplasia, bilateral laparoscopic adrenalectomy may need to be considered. (See "Treatment of primary aldosteronism".)

PRIMARY ALDOSTERONISM WITH SEIZURES AND NEUROLOGIC ABNORMALITIES (PASNA) — Germline pathogenic variants in CACNA1D (encoding an L-type calcium channel) have been reported in three children with primary aldosteronism, seizures, and neurologic abnormalities [35,36]. PASNA is caused by de novo germline pathogenic variants in CACNA1D. The severe neurologic abnormalities do not allow these individuals to reproduce, and thus, although due to a germline pathogenic variant, it is not technically a familial form of primary aldosteronism. In addition, a missense CACNA1D germline pathogenic variant was reported in a patient affected by autism and epilepsy [37]. The laboratories that provide clinical genetic testing can be found in the Genetic Testing Registry.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary aldosteronism".)

SUMMARY AND RECOMMENDATIONS

Glucocorticoid-remediable aldosteronism (GRA) or familial hyperaldosteronism (FH) type I is an inherited form (autosomal dominant) of hyperaldosteronism and is usually associated with bilateral adrenal hyperplasia. (See 'Familial hyperaldosteronism type I (FH type I) or glucocorticoid-remediable aldosteronism (GRA)' above.)

The mutation in patients with GRA is fusion of the promoter region of the gene for CYP11B1 and the coding sequence of CYP11B2; these patients are biochemically unique in having markedly increased levels of 18-oxocortisol and 18-hydroxycortisol. (See 'Pathophysiology' above.)

GRA should be suspected as the cause of primary aldosteronism when there is a positive family history and the onset of hypertension is before age 21 years. More than one-half of patients are normokalemic at the time of diagnosis, although they may develop marked hypokalemia after the administration of a thiazide diuretic. Patients with GRA are at increased risk for hemorrhagic stroke, due primarily to ruptured intracranial aneurysms. (See 'Clinical characteristics' above.)

We suggest treating GRA with physiologic doses of a glucocorticoid (Grade 2B). This will correct the overproduction of aldosterone by suppressing corticotropin (ACTH) and will usually lower the blood pressure toward or to normal and correct hypokalemia (if present). Mineralocorticoid receptor antagonists may be equally effective. (See 'Treatment' above.)

FH type II should be considered in all patients with primary aldosteronism who have family members with hypertension. The hypertensive family members should be offered case-detection testing with measurement of plasma aldosterone concentration and plasma renin activity. (See 'Clinical features' above.)

FH type II is transmitted in an autosomal dominant fashion. Germline CLCN2 chloride channel pathogenic variants may be responsible for all or some of the individuals who have been classified at FH type II. (See 'Pathogenic variants' above.)

Patients with FH type II should be treated exactly the same as patients with sporadic primary aldosteronism. (See 'Management' above.)

FH type III is caused by germline pathogenic variants in the potassium channel subunit KCNJ5. In addition, somatic mutations in KCNJ5 have been identified in aldosterone-producing adenomas. (See 'Mutations in KCNJ5 gene' above.)

Commercially available testing for germline KCNJ5 pathogenic variants is now available. This rare subtype of primary aldosteronism should be suspected in children with hyperaldosteronism and in families with more than one member with primary aldosteronism. (See 'Evaluation and diagnosis' above.)

FH type III appears to have a variable clinical phenotype. However, in selected cases of refractory disease associated with massive bilateral adrenal hyperplasia, bilateral laparoscopic adrenalectomy may need to be considered. (See 'Therapy' above.)

FH type IV is caused by germline mutations in CACNA1H (encoding a T-type calcium channel).

Commercially available testing for germline CACNA1H mutations is now available. This rare subtype of primary aldosteronism should be suspected in children with hyperaldosteronism and in families with more than one member with primary aldosteronism. (See 'Evaluation and diagnosis' above.)

In selected patients with FH type IV who have refractory disease associated with massive bilateral adrenal hyperplasia, bilateral laparoscopic adrenalectomy may need to be considered. (See 'Therapy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Norman M Kaplan, MD, who contributed to earlier versions of this topic review.

  1. Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J 1966; 95:1109.
  2. Lifton RP, Dluhy RG, Powers M, et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992; 355:262.
  3. Rich GM, Ulick S, Cook S, et al. Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann Intern Med 1992; 116:813.
  4. McMahon GT, Dluhy RG. Glucocorticoid-remediable aldosteronism. Cardiol Rev 2004; 12:44.
  5. Torpy DJ, Gordon RD, Lin JP, et al. Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. J Clin Endocrinol Metab 1998; 83:3214.
  6. Mulatero P, Tizzani D, Viola A, et al. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms). Hypertension 2011; 58:797.
  7. Lifton RP, Dluhy RG, Powers M, et al. Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase. Nat Genet 1992; 2:66.
  8. Litchfield WR, Coolidge C, Silva P, et al. Impaired potassium-stimulated aldosterone production: a possible explanation for normokalemic glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 1997; 82:1507.
  9. Fallo F, Pilon C, Williams TA, et al. Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism. J Hum Hypertens 2004; 18:47.
  10. Litchfield WR, Anderson BF, Weiss RJ, et al. Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension 1998; 31:445.
  11. Botero-Velez M, Curtis JJ, Warnock DG. Brief report: Liddle's syndrome revisited--a disorder of sodium reabsorption in the distal tubule. N Engl J Med 1994; 330:178.
  12. Jamieson A, Inglis GC, Campbell M, et al. Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents. Arch Dis Child 1994; 71:40.
  13. Jonsson JR, Klemm SA, Tunny TJ, et al. A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. Biochem Biophys Res Commun 1995; 207:565.
  14. Mulatero P, Veglio F, Pilon C, et al. Diagnosis of glucocorticoid-remediable aldosteronism in primary aldosteronism: aldosterone response to dexamethasone and long polymerase chain reaction for chimeric gene. J Clin Endocrinol Metab 1998; 83:2573.
  15. Gates LJ, Benjamin N, Haites NE, et al. Is random screening of value in detecting glucocorticoid-remediable aldosteronism within a hypertensive population? J Hum Hypertens 2001; 15:173.
  16. Dluhy RG, Anderson B, Harlin B, et al. Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood. J Pediatr 2001; 138:715.
  17. Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101:1889.
  18. Stowasser M, Bachmann AW, Huggard PR, et al. Treatment of familial hyperaldosteronism type I: only partial suppression of adrenocorticotropin required to correct hypertension. J Clin Endocrinol Metab 2000; 85:3313.
  19. Tan ST, Boyle V, Elston MS. Systematic Review of Therapeutic Agents and Long-Term Outcomes of Familial Hyperaldosteronism Type 1. Hypertension 2023; 80:1517.
  20. Pallauf A, Schirpenbach C, Zwermann O, et al. The prevalence of familial hyperaldosteronism in apparently sporadic primary aldosteronism in Germany: a single center experience. Horm Metab Res 2012; 44:215.
  21. Scholl UI, Stölting G, Schewe J, et al. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet 2018; 50:349.
  22. Fernandes-Rosa FL, Daniil G, Orozco IJ, et al. A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat Genet 2018; 50:355.
  23. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf) 2007; 66:607.
  24. Geller DS, Zhang J, Wisgerhof MV, et al. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 2008; 93:3117.
  25. Choi M, Scholl UI, Yue P, et al. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science 2011; 331:768.
  26. Mulatero P, Tauber P, Zennaro MC, et al. KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism. Hypertension 2012; 59:235.
  27. Scholl UI, Nelson-Williams C, Yue P, et al. Hypertension with or without adrenal hyperplasia due to different inherited mutations in the potassium channel KCNJ5. Proc Natl Acad Sci U S A 2012; 109:2533.
  28. Adachi M, Muroya K, Asakura Y, et al. Discordant genotype-phenotype correlation in familial hyperaldosteronism type III with KCNJ5 gene mutation: a patient report and review of the literature. Horm Res Paediatr 2014; 82:138.
  29. Monticone S, Tetti M, Burrello J, et al. Familial hyperaldosteronism type III. J Hum Hypertens 2017; 31:776.
  30. Monticone S, Hattangady NG, Penton D, et al. a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism type III. J Clin Endocrinol Metab 2013; 98:E1861.
  31. Charmandari E, Sertedaki A, Kino T, et al. A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension. J Clin Endocrinol Metab 2012; 97:E1532.
  32. Mussa A, Camilla R, Monticone S, et al. Polyuric-polydipsic syndrome in a pediatric case of non-glucocorticoid remediable familial hyperaldosteronism. Endocr J 2012; 59:497.
  33. Scholl UI, Stölting G, Nelson-Williams C, et al. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife 2015; 4:e06315.
  34. Daniil G, Fernandes-Rosa FL, Chemin J, et al. CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism. EBioMedicine 2016; 13:225.
  35. Scholl UI, Goh G, Stölting G, et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet 2013; 45:1050.
  36. Semenova NA, Ryzhkova OR, Strokova TV, Taran NN. [The third case report a patient with primary aldosteronism, seizures, and neurologic abnormalities (PASNA) syndrome de novo variant mutations in the CACNA1D gene]. Zh Nevrol Psikhiatr Im S S Korsakova 2018; 118:49.
  37. Pinggera A, Mackenroth L, Rump A, et al. New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy. Hum Mol Genet 2017; 26:2923.
Topic 122 Version 27.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟