Early cardiac morphologic and functional changes in neurofibromatosis type 1 hypertensives: an echocardiographic and tissue Doppler study

Tedesco, Michele Adolfo; Salvo, Giovanni Di; Natale, Francesco; Graziano, Luisa; Grassia, Carolina; Calabrò, Raffaele; Lama, Giuliana

doi:10.1016/j.ijcard.2004.03.028

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…In our study, TVR was increased to a similar degree in both the pre‐eclamptic IUGR and the normotensive IUGR groups, but the MAP and stroke volume were lower in the normotensive IUGR group, which is consistent with either a relatively reduced LV contractility, reduced diastolic filling or both. DTI allows the detection of abnormalities of LV longitudinal function which precede abnormalities of transverse systolic function in ischemia22, cardiomyopathies, essential hypertension and LV hypertrophy22–24. Systolic function assessed using the DTI systolic (S′) peak velocity25 was significantly lower in the pre‐eclamptic IUGR group, suggesting relatively reduced LV contractility in this group26.…”

Section: Discussionmentioning

confidence: 99%

Maternal cardiac function in normotensive and pre‐eclamptic intrauterine growth restriction

Bamfo

Kametas

Chambers

et al. 2008

Ultrasound in Obstet & Gyne

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Section: Discussionmentioning

confidence: 99%

Maternal cardiac function in normotensive and pre‐eclamptic intrauterine growth restriction

Bamfo

Kametas

Chambers

et al. 2008

Ultrasound in Obstet & Gyne

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“…Our findings of early asymptomatic alterations in cardiac function deserve some comments as well. Both morphologic and functional cardiac alterations were previously reported in young patients with NF1 with hypertension 26,27 . However, a later study describing cardiac characterization of NF1 with or without large deletions of the NF1 gene, reported no impairment of cardiac systolic or diastolic function 28 .…”

Section: Discussionmentioning

confidence: 60%

Functional and morphological cardiovascular alterations associated with neurofibromatosis 1

Cutruzzolà

Irace

Frazzetto

et al. 2020

Sci Rep

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Subjects with Neurofibromatosis 1 (NF1) develop vascular complications. The protein product of the gene affected in NF1, neurofibromin, physiologically modulates endothelial function and preserves vascular and myocardial structure. Our study aimed to verify whether subjects with NF1 have early, preclinical abnormalities of carotid artery structure, brachial artery function, and cardiac function. We recruited 22 NF1 subjects without previous cardiovascular events and 22 healthy control subjects. All subjects underwent measurement of carotid artery intima-media thickness (IMT), evaluation of brachial artery endothelial function after ischemia and exercise, and cardiac function. Mean IMT was 543 ± 115 μ in NF1 subjects and 487 ± 70 μ in Controls (p < 0.01). Endothelial function was significantly dumped in NF1 subjects. The dilation after ischemia and exercise was respectively 7.5(± 4.8)% and 6.7(± 3.0)% in NF1 versus 10.5(± 1.2)% and 10.5(± 2.1)% in control subjects (p < 0.02; p < 0.002). Left ventricular systolic function assessed by Global Longitudinal Strain was significantly different between NF1 subjects and Controls: − 19.3(± 1.7)% versus − 21.5(± 2.7)% (p < 0.008). These findings demonstrate that NF1 patients have early morphological and functional abnormalities of peripheral arteries and systolic cardiac impairment and suggest the need for a tight cardiovascular risk evaluation and primary prevention in subjects with NF1. Neurofibromatosis 1 (NF1) is a common genetic disease, affecting approximately 1 in 3,500 subjects. It has an autosomal dominant inheritance with complete penetrance, variable expression, and a high rate of new mutations. The disease is characterized by cafe-au-lait spots, dermal neurofibromas, skeletal dysplasia, Lish nodules, and optic glioma 1. Neurofibromin (encoded by the NF1 gene) is a modulator of cell growth, downregulates ras signaling, and its loss of function promotes cellular proliferation 2. For these reasons, subjects with NF1 have increased risk for malignancies like peripheral nerve sheath tumor, leukemia, and rhabdomyosarcoma. Furthermore, they may develop vascular complications as renal artery stenosis with secondary hypertension, aneurysm, arterial stenosis/occlusion, myocardial infarction, and cerebral or visceral infarcts arteriovenous fistulae 3. The vascular involvement does not seem directly linked to the proliferation and malignant transformation of neural-crest derivatives 2. Though pathogenesis of vascular lesions in NF1 remains unclear, previous studies in murine models and humans demonstrated that neurofibromin is expressed in the endothelial cells and vascular smooth muscle cells as well 2,4. Therefore NF1 vasculopathy might be the consequence of a direct involvement in vascular layers 5. Cardiac alterations have also been under the spotlight in NF1. The neurofibromin protein is physiologically involved in cardiac development 6. Besides, microdeletions of the NF1 gene often involve the nearby SUZ12 and CENTA2 genes, whose haploinsufficiency may also influence c...

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“…It has been widely demonstrated that the protein Na v 1.5 encoded by the SCN5A gene is an essential controller of cardiac excitability, and recent studies underlined that loss of function mutations in SCN5A is associated with increased cardiac dimensions and reduced contractility (van Hoorn et al., 2012). Another study by Tedesco and colleagues highlighted that also NF1 patients even without arterial hypertension can show alterations in Doppler tissue imaging (Tedesco et al., 2005). Understanding the clinical significance of individual SCN5A mutations is challenging, given the extreme clinical variability seen in patients with SCN5A mutations (Kyndt et al., 2001; Six et al., 2008), the variability in the types of mutations and locations within the gene, the number of mutations, genetic heterogeneity, and the fact that some of these variants are found in the general population (Juang et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis

et al. 2019

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In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction.

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Early cardiac morphologic and functional changes in neurofibromatosis type 1 hypertensives: an echocardiographic and tissue Doppler study

Cited by 6 publications

References 23 publications

Maternal cardiac function in normotensive and pre‐eclamptic intrauterine growth restriction

Maternal cardiac function in normotensive and pre‐eclamptic intrauterine growth restriction

Functional and morphological cardiovascular alterations associated with neurofibromatosis 1

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis

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