Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1

Abstract

Although it is well recognized that a peripheral vasculopathy may occur in patients with neurofibromatosis 1 (NF1), it is unclear whether cardiovascular abnormalities are more common. We reviewed the frequency of cardiovascular abnormalities, in particular, cardiovascular malformations (CVMs), among 2322 patients with definite NF1 in the National Neurofibromatosis Foundation International Database from 1991-98. Cardiovascular malformations were reported in 54/2322 (2.3%) of the NF1 patients, only 4 of whom had Watson syndrome or NF1-Noonan syndrome. There was a predominance of Class II "flow" defects [Clark, 1995: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. p 60-70] (43/54, 80%) among the NF1 patients with CVMs. Pulmonic stenosis, that was present in 25 NF1 patients, and aortic coarctation, that occurred in 5, constitute much larger proportions of all CVMs than expected. Of interest was the paucity of Class I conotruncal defects (2 patients with tetralogy of Fallot), and the absence of atrioventricular canal, anomalous pulmonary venous return, complex single ventricle and laterality defects. Besides the 54 patients with CVMs, there were 27 patients with other cardiac abnormalities (16 with murmur, 5 with mitral valve prolapse, 1 with intracardiac tumor, and 5 with electrocardiogram abnormalities). No patient in this study had hypertrophic cardiomyopathy. There were 16 patients who had a peripheral vascular abnormality without an intracardiac CVM, plus an additional 4 patients among those with a CVM who also had a peripheral vascular abnormality.

Increased rate of missense/in-frame mutations in individuals with NF1-related pulmonary stenosis: a novel genotype–phenotype correlation

“…In 28 of them, information regarding the cardiac status was available. The difference in PS prevalence between the NFNS group and the NF1 group, was shown to be driven by the NFNS patients with non-truncating mutation: 66.7% (8/12) of NFNS with non-truncating mutation patients had PS vs 1.1% (25/2322) 23 in NF1 (Po0.001, LR ¼ 55); only 6.2% (1/16) NFNS patients with a truncating mutation had PS, not significantly different from NF1 patients: 1.1% (P ¼ 0.164) ( Table 1).…”

“…No clear genotype-phenotype correlation for the cardiac phenotype in NF1 and/or NFNS has been suggested, although a trend of association was found between heart defects, NFNS and in-frame/single amino-acid substitution. 18 Given the previous observations of an increased prevalence of nontruncating mutations in NFNS, 18 of an excess of PS in patients with NF1, 23 particularly in patients with the non-truncating 3 bp exon 17 deletion, 9 we hypothesized that non-truncating mutations in NF1 may be responsible for particular disease features, especially those which overlap with other Ras-MAPK disorders. Here, we report our analysis of mutation type in patients with PS and NF1, WS or NFNS.…”

“…23 PS is the most common cardiac defect in NF1 and represented almost 50% of the cardiac malformations in the largest series of NF1 cases with cardiac problems (25/54). 23 At this frequency, PS is six times more prevalent in NF1 patients compared with the general population.…”

“…23 PS is the most common cardiac defect in NF1 and represented almost 50% of the cardiac malformations in the largest series of NF1 cases with cardiac problems (25/54). 23 At this frequency, PS is six times more prevalent in NF1 patients compared with the general population. No clear genotype-phenotype correlation for the cardiac phenotype in NF1 and/or NFNS has been suggested, although a trend of association was found between heart defects, NFNS and in-frame/single amino-acid substitution.…”

Ruptured Extracranial Vertebral Artery Aneurysm Associated With Neurofibromatosis Type 1

“…The frequency of vascular lesions in NF1 patients is hard to define because screening studies are not routinely performed, but the prevalence of vascular lesions in large series is 0.4% to 6.4%. 3,4,11,14) Renal artery lesions are most common (41%) and are more often stenotic than aneurysmal, but carotid artery, vertebral artery (VA), and cerebral artery aneurysms, reported in 46 patients, occur in the third decade of life and are more common in women. The renal artery is most frequently involved, resulting in renovascular hypertension.…”