Analysis of 786 NF1 mutation-positive subjects with clinical diagnosis of neurofibromatosis type 1 (NF1) allowed to identify the heterozygous c.5425C4T missense variant (p.Arg1809Cys) in six (0.7%) unrelated probands (three familial and three sporadic cases), all exhibiting a mild form of disease. Detailed clinical characterization of these subjects and other eight affected relatives showed that all individuals had multiple cafè-au-lait spots, frequently associated with skinfold freckling, but absence of discrete cutaneous or plexiform neurofibromas, Lisch nodules, typical NF1 osseous lesions or symptomatic optic gliomas. Facial features in half of the individuals were suggestive of Noonan syndrome. Our finding and revision of the literature consistently indicate that the c.5425C4T change is associated with a distinctive, mild form of NF1, providing new data with direct impact on genetic counseling and patient management.

We report 281 individuals carrying a pathogenic recurrent NF1

The aim of the study was to evaluate the prevalence of pheochromocytoma (PHEO) in patients with neurofibromatosis type 1 (NF1), and to analyze the behavior of some anthropometric and cardiovascular parameters. In 48 consecutive NF1 patients, urinary metanephrines and vanillylmandelic acid excretion were assessed. The body mass index (BMI), waist circumference (WC), ambulatory blood pressure monitoring (ABPM), echocardiography and ultrasound carotid arterial wall evaluation were performed. In NF1 patients, 11 (29.3%) had arterial hypertension, 7 (14.6%) had a PHEO. Four (57%) NF1 patients with PHEO were symptomatic at the diagnosis. In PHEO-NF1 patients, we revealed a lower BMI and WC values with respect to NF1 patients without PHEO and normal subjects (NSs) (p < 0.05), respectively. The nocturnal non-dipping pattern at the ABPM was present in 40.4% of NF1 patients, and in particular this phenomenon was present in PHEO-NF1 patients (71.4%). Left ventricular mass index and intima media thickness were significantly higher in NF1 patients as compared to NS (p < 0.05), particularly in NF1-PHEO patients (p < 0.05). In conclusions, these findings revealed high prevalence of PHEO in NF1 patients and suggest that, in addition to blood pressure, humoral factors (increased sympathetic activity or neurofibromin), influence the pathogenesis of remodeling of cardiovascular system.