Liddle syndrome: clinical and genetic profiles

Cui, Yunying; Tong, Anli; Jiang, Jun; Wang, Fen; Li, Chunyan

doi:10.1111/jch.12949

Cited by 50 publications

(40 citation statements)

References 10 publications

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“…LS patients lacking a family history have also been noted. Cui et al reported that de novo pathogenic variants accounted for 50% of cases, 26 and Yang et al found that 86% index cases with LS had a family history. 25 Consistent with our review in this study, only 4 (10%) pediatric cases were isolated with de novo pathogenic variants.…”

Section: Discussionmentioning

confidence: 99%

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Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension

Fan

Pan

Zhang

et al. 2020

American Journal of Hypertension

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BACKGROUND Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of epithelial sodium channel (ENaC)-gene-positive LS cases to conclude the clinical genetic features of LS in childhood. METHODS Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years. RESULTS Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors. CONCLUSIONS This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents are important to prevent the development of hypertensive end-organ disease.

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Section: Discussionmentioning

confidence: 99%

“… 25 Consistent with our review in this study, only 4 (10%) pediatric cases were isolated with de novo pathogenic variants. 13 , 26 , 27 Although a family history of childhood hypertension is a clue for pediatric LS, physicians should consider the isolated LS individual with a de novo pathogenic variant.…”

Section: Discussionmentioning

confidence: 99%

Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension

Fan

Pan

Zhang

et al. 2020

American Journal of Hypertension

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“…On average, hypertension develops around the second decade of life (15.5 ± 3.3 years) [10], with variation in the age of onset and severity of hypertension [6]. Without treatment, subjects will present with complications of severe hypertension during the third or fourth decade of life.…”

Section: Liddle Syndromementioning

confidence: 99%

The Research Progress of Monogenic Inherited Hypertension

Liu¹,

Yin²

2020

Rare Diseases

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Monogenic inherited hypertension, which is caused by a single gene mutation, generally conforms to the Mendel's law, but its phenotype is affected by environmental factors as well. This type of hypertension is characterized by early onset (more common in adolescents), family history, severe hypertension, or refractory hypertension. It is often accompanied by abnormal hormone level and biochemical indicators, including low activity of plasma renin, abnormal potassium, and acidbase metabolization disorder. For adolescents with a family history of moderate to severe hypertension, hormone level (including plasma renin-angiotensin-aldosterone, cortisol, and sex hormone) and blood electrolytes should be measured and the detailed diagnosis should be determined according to medical history, physical signs, and test results. Currently, 17 kinds of monogenic hereditary hypertension have been clearly determined. Thanks to the development of gene detection technology, the diagnostic level of monogenic inherited hypertension has greatly improved and the pathogenesis has been gradually clarified. Our review mainly discussed the research progress in this field.

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“…Since increased luminal ENaC in the distal nephron is the common final mechanism for MR-mediated sodium reabsorption, Liddle syndrome resembles states of mineralocorticoid excess. The classical clinical presentation is severe hypertension in a young patient, with hypokalemia and metabolic alkalosis, in the setting of suppressed renin; however, unlike PA, aldosterone levels are low or undetectable and the syndrome does not improve with MR antagonist therapy [ 73 , 74 , 75 , 76 ]. The diagnosis of Liddle syndrome can be confirmed by genetic sequencing of the SCNN1B and SCNN1G genes, which encode for the β and γ subunits of ENaC [ 75 ], or the SCNN1A gene [ 77 ], and the treatment of choice are ENaC inhibitors such as amiloride or triamterene [ 74 ].…”

Section: Liddle Syndromementioning

confidence: 99%

The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor

Baudrand

Vaidya

2018

IJMS

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A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH) may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH. Classically, the individual causes of LRH have been considered to be rare diseases; however, recent advances suggest that there are milder and “non-classical” variants of many LRH-inducing conditions. In this regard, our understanding of the underlying genetics and mechanisms accounting for LRH, and therefore, potentially the pathogenesis of a large subset of essential hypertension, is evolving. This review will discuss the potential causes of LRH, with a focus on implicated genetic mechanisms, the expanding recognition of non-classical variants of conditions that induce LRH, and the role of the mineralocorticoid receptor in determining this phenotype.

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Liddle syndrome: clinical and genetic profiles

Cited by 50 publications

References 10 publications

Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension

Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension

The Research Progress of Monogenic Inherited Hypertension

The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor

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