Blood pressure and cardiovascular involvement in children with neurofibromatosis type1

Lama, Giuliana; Graziano, Luisa; Calabrese, Elvira; Grassia, Carolina; Rambaldi, Pier Francesco; Cioce, Fabrizio; Tedesco, Michele Adolfo; Salvo, Giovanni Di; Esposito-Salsano, Maria

doi:10.1007/s00467-003-1397-5

Cited by 36 publications

(13 citation statements)

References 36 publications

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“…[8] Many reports in the literature have shown cardiac involvement in NF1, including valvular pulmonary stenosis, branch peripheral pulmonary stenosis, atrial and ventricular septal defects, coarctation of the aorta (thoracic and abdominal), and hypertrophic cardiomyopathy. [3,[9][10][11] In a recent study, Lin et al [10] reported that the prevalence rate of cardiovascular abnormalities in patients with NF1 is low (2.3%). However, in another study, Lama et al [11] described cardiac abnormalities in 13 of 69 patients (18.8%) with NF1.…”

Section: Discussionmentioning

confidence: 99%

“…[3,[9][10][11] In a recent study, Lin et al [10] reported that the prevalence rate of cardiovascular abnormalities in patients with NF1 is low (2.3%). However, in another study, Lama et al [11] described cardiac abnormalities in 13 of 69 patients (18.8%) with NF1. They found 4 patients with cardiac heart disease, 2 patients with mild mitral regurgitation, 2 patients with mild aortic regurgitation, 2 patients with hypertrophic cardiomyopathy, and 1 patient with mitral valve prolapse.…”

Section: Discussionmentioning

confidence: 99%

“…Lama et al [11] reported 4 patients with cardiac heart disease; 2 had secundum ASD, 1 had pulmonary artery stenosis, and 1 had coarctation thoracic aorta. Additionally, in published series, the frequency of congenital heart defects ranges from 0.4% to 6.4%.…”

Section: Discussionmentioning

confidence: 99%

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Neurofibromatosis type 1 and cardiac manifestations

İncecik

Hergüner

Erdem

et al. 2015

Arch Turk Soc Cardiol

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Neurofibromatosis type 1 and cardiac manifestations

İncecik

Hergüner

Erdem

et al. 2015

Arch Turk Soc Cardiol

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“…Our literature review found six cohorts from seven articles that considered the prevalence of pre-hypertension and hypertension in patients with NF-1; 7.4–22% and 6.1–23.4% for pre-hypertension and hypertension, respectively ( 16 – 22 ). In five of the studies ( 16 – 20 , 22 ), the patients were children and young adults (1.5–25 years) with a high prevalence of early-onset hypertension, suggesting the necessity of regular blood pressure monitor in young patients with NF-1, and the patients in the study conducted by Zinnamosca et al ( 21 ) were middle-aged adults. Dubov et al ( 19 ) found the lowest prevalence of hypertension (6.1%) by measuring office blood pressure of 114 patients with NF-1, whereas Tedesco et al ( 17 ) found the highest prevalence (23.4%) using the same method and criteria in a different cohort of 64 patients with NF-1.…”

Section: Discussionmentioning

confidence: 98%

Identification of NF1 Frameshift Variants in Two Chinese Families With Neurofibromatosis Type 1 and Early-Onset Hypertension

Zhang

Liu

et al. 2021

Front. Pediatr.

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Background: Neurofibromatosis type 1 (NF-1) is a common autosomal dominant disorder caused by mutations in the NF1 gene. It is characterized by multiple café-au-lait macules, cutaneous neurofibromas, optic glioma, Lisch nodules, and axillary and inguinal freckling. The aim of this study was to investigate NF1 mutations in two Chinese families with NF-1 who presented with early-onset hypertension, and to determine the prevalence of hypertension associated with NF-1 to better understand this complication.Methods: Whole-exome sequencing was performed for the probands with NF-1 from two unrelated families. Possible pathogenic mutation was predicted by bioinformatic tools. Sanger sequencing was used to confirm candidate variants in all available individuals for familial co-segregation analysis. We also performed a systematic literature review of studies that reported the prevalence of hypertension in patients with NF-1.Results: In family 1, a recurrent mutation c.6789_6792delTTAC in NF1 was identified in the proband but in no other family members, indicating that this is a de novo mutation. In family 2, a novel mutation c.6934_6936delGCAinsTGCT in NF1 was detected in the proband and two other family members, which co-segregated with the disease phenotype within the family. Both mutations were predicted to be pathogenic by bioinformatic analysis. We found hypertension was a relatively common complication of NF-1, with a prevalence range of 6.1–23.4%. Ambulatory blood pressure monitoring is a stable method for detecting initial alterations of the blood pressure pattern, particularly for pre-hypertension.Conclusions: We identified one recurrent (c.6789_6792delTTAC) and one novel frame-shift mutation (c.6934_6936delGCAinsTGCT) in two unrelated families with NF-1 using whole-exome sequencing. In consideration of phenotypic heterogeneity in NF-1, genetic testing is a robust tool which helps early and accurate diagnosis. Because hypertension is not a rare complication of NF-1, routine screening for hypertension in patients with NF-1, especially children and adolescents, is important to avoid serious cardiovascular events.

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“…In addition, clinical manifestations include learning disabilitiesand an increased risk of malignancy [1–3]. Hypertension and precocious puberty (PP) are frequent complications in NF occurring in approximately 16% [4,5] and 2,5–5% [6–8] respectively. More than a half of hypertensive NF1 patients do not have one of the two well-known causes either renal artery stenosis or pheochromocytoma [9].…”

Section: Introductionmentioning

confidence: 99%

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

et al. 2015

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BackgroundNeurofibromatosis type I (NF1, MIM#162200) is a relatively frequent genetic condition, which predisposes to tumor formation. Apart from tumors, individuals with NF1 often exhibit endocrine abnormalities such as precocious puberty (2,5–5% of NF1 patients) and some cases of hypertension (16% of NF1 patients). Several cases of adrenal cortex adenomas have been described in NF1 individuals supporting the notion that neurofibromin might play a role in adrenal cortex homeostasis. However, no experimental data were available to prove this hypothesis.Materials and MethodsWe analysed Nf1Prx1 mice and one case of adrenal cortical hyperplasia in a NF1patient.ResultsIn Nf1Prx1 mice Nf1 is inactivated in the developing limbs, head mesenchyme as well as in the adrenal gland cortex, but not the adrenal medulla or brain. We show that adrenal gland size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed deregulation of multiple proteins, including steroidogenic acute regulatory protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol into steroid making mitochondria. This was associated with a marked upregulation of MAPK pathway and a female specific increase of cAMP concentration in murine adrenal lysates. Complementarily, we characterized a patient with neurofibromatosis type I with macronodular adrenal hyperplasia with ACTH-independent cortisol overproduction. Comparison of normal control tissue- and adrenal hyperplasia- derived genomic DNA revealed loss of heterozygosity (LOH) of the wild type NF1 allele, showing that biallelic NF1 gene inactivation occurred in the hyperplastic adrenal gland.ConclusionsOur data suggest that biallelic loss of Nf1 induces autonomous adrenal hyper-activity. We conclude that Nf1 is involved in the regulation of adrenal cortex function in mice and humans.

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Blood pressure and cardiovascular involvement in children with neurofibromatosis type1

Cited by 36 publications

References 36 publications

Neurofibromatosis type 1 and cardiac manifestations

Neurofibromatosis type 1 and cardiac manifestations

Identification of NF1 Frameshift Variants in Two Chinese Families With Neurofibromatosis Type 1 and Early-Onset Hypertension

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

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