Racial/Ethnic Differences in Pediatric Brain Tumor Diagnoses in Patients with Neurofibromatosis Type 1.

OBJECTIVE: To evaluate evidence for differences in pediatric brain tumor diagnoses by race and ethnicity using a cross-sectional study design in individuals with neurofibromatosis type 1 (NF1). STUDY DESIGN: Subjects with NF1 were ascertained from the NF1 Patient Registry Initiative and through a clinical record database of patients at a large academic medical center. Logistic regression was employed to calculate ORs and 95% CIs to analyze differences in the odds of brain tumor diagnosis by race (White, Black, Asian, other/unknown) and ethnic (Hispanic vs non-Hispanic) groups. RESULTS: Data from a total of 1546, 629, and 2038 individuals who were ascertained from the NF1 Patient Registry Initiative, clinical records, and pooled datasets were analyzed, respectively. After adjusting for birth year, we observed a significantly reduced odds of brain tumor diagnoses in individuals self-identified or clinically reported as Black (OR = 0.13, 95% CI 0.05-0.31), Asian (OR = 0.15, 95% CI 0.04-0.64), and other/unknown (OR = 0.61, 95% CI 0.41-0.93) race compared with those with reported as White race. There was no significant difference in the odds of pediatric brain tumor diagnosis by Hispanic ethnicity. CONCLUSIONS: Consistent with prior smaller studies, these data suggest that pediatric brain tumor diagnoses vary by race in individuals with NF1. Reasons underlying observed differences by race warrant further investigation.

Validity of participant-reported diagnoses in an online patient registry: a report from the NF1 Patient Registry Initiative.

BACKGROUND: With increased internet accessibility worldwide, it is now possible to assemble individuals with rare diseases through web-based patient registries. However, the validity of participant-reported medical diagnoses is unknown. The objective of this study was to evaluate the accuracy of participant-reported Neurofibromatosis Type 1 (NF1) diagnoses among participants in the NF1 Patient Registry Initiative (NPRI). METHODS: Subjects enrolled in the NPRI from 5/17/2011 to 7/7/2014 were included. Medical records (MRs) were obtained for participants who returned medical record release forms (MRRFs) during the study period. Participants were classified as having definite, probable, suspected, or no NF1 diagnosis based on MR information. To assess whether a returned MRRF served as a reliable marker of MR-documented NF1, we calculated the positive predictive value (PPV) as the proportion of individuals with MR-documented NF1 among those from whom MRs were obtained. We further examined whether a returned MRRF predicted the number of reported NF1 clinical signs in multivariable linear regression analyses. RESULTS: A total of 1456 individuals were included in the analyses. Of 416 individuals who returned MRRFs, 205 MRs were reviewed within the study period. The PPV ranged from 72.0 to 98.5% when including definite or definite/probable/suspected cases, respectively. The mean number of reported NF1 clinical signs was similar between those who returned (mean=3.3 ± 1.2) and did not return (mean=3.2 ± 1.3) their MRRFs. MRRF return was not a significant predictor of the number of NF1 clinical signs after adjusting for covariates. CONCLUSION: These data strongly suggest that individuals enrolling in the NPRI accurately report their NF1 diagnosis.

A novel NF1 frame-shift mutation (c.702_703delGT) in a Chinese family with neurofibromatosis type 1.

This study aimed to characterize the clinical features of a Chinese pedigree with neurofibromatosis type 1 (NF1) and to identify mutations in the NF1 gene. In this three-generation family containing 8 members, 5 had been diagnosed with NF1 and the others were asymptomatic. All members of the family underwent complete medical examinations. Molecular genetic analyses were performed on all subjects included in the study. All exons of NF1 were amplified by polymerase chain reaction, sequenced, and compared with a reference database. Possible changes in function of the protein induced by amino acid variants were predicted by bioinformatic analysis. In this family, the 5 patients presented different clinical phenotypes, but all manifested typical café-au-lait macules. One novel frame-shift mutation, c.702_703delGT, in exon 7 of NF1 was identified in all affected family members, but not in the unaffected family members or in 102 normal controls. This mutation generates a premature stop codon at amino acid position 720. Additionally, a synonymous mutation c.702 G>A was found in 3 family members, including 2 affected and 1 normal individuals. In conclusion, our study suggests that a novel c.702_703delGT frame-shift mutation in NF1 is likely to be responsible for the pathogenesis of NF1 in this family. To the best of our knowledge, it is the first time that a c.702_703delGT mutation has been identified in a family with neurofibromatosis type 1.

Objective assessment of nasality in Flemish adults with neurofibromatosis type 1.

When characterizing the speech of a patient with neurofibromatosis type 1 (NF1), hypernasality is often mentioned. As few studies applied technically assisted evaluations of nasality in NF1 patients, the aim of the present study was to document the nasal resonance of adults with NF1 using nasometry. The nasometric data obtained from the NF1 patients were compared with the nasalance scores of a healthy control group and with normative data. The final study group consisted of 24 adult NF1 patients and 16 controls, all living in the East Flemish part of Belgium. Nasalance scores were obtained while the participants sustained three vowels (/a:/, /i./, and /u./) and one consonant (/m/) and read three standard nasalance passages. Despite the inter- and intra-subject variability, we observed that NF1 patients as a group exhibited higher mean nasalance scores than controls. This finding was especially clear in males. Potential genotype-phenotype correlations between NF1 mutation type and hypernasality were examined but could not be demonstrated. Conversely, comparison of the nasometric data obtained from the NF1 patients with magnetic resonance imaging findings showed some degree of interesting correlation. We conclude that, notwithstanding the small sample size for some analyses, nasality is an area of interest in the NF1 population. As altered nasality influences speech intelligibility, nasality requires attention during follow-up visits, particularly when it concerns a male NF1 patient.

Branch retinal vein occlusion in a Japanese patient with neurofibromatosis 1.

BACKGROUND: To report an Asian patient with branch retinal vein occlusion secondary to neurofibromatosis 1. CASE: A 64-year-old woman presented with a loss of vision in her right eye of 9-month duration. A diagnosis of neurofibromatosis 1 was made. A general medical examination showed no abnormalities except the signs of neurofibromatosis 1. OBSERVATIONS: Fundus examination of the right eye revealed irregularities of the venous caliber, partial sheathing of the corresponding vein and macular edema. Multiple dilated and tortuous collateral channels and an arteriovenous communication bridged the perfused and nonperfused retina. Fundus examination of the left eye showed a tortuous vein in the temporal region of the fovea. Fluorescein angiography of the right eye confirmed delayed filling in a superotemporal artery and in the corresponding vein. The temporal region of the fovea had large areas of capillary loss. The collaterals were tortuous and mimicked a neovascularization. Fluorescein angiography of the left eye confirmed that the vein in the temporal part of the fovea was tortuous and not leaking. A diagnosis of branch retinal vein occlusion of the superotemporal vein was made. CONCLUSIONS: Neurofibromatosis 1 should be considered in the differential diagnosis of retinal vascular occlusive disease without other risk factors.

[Type I neurofibromatosis presenting as a progressive cervical myelopathy. The first case reported in Kaxinawa Indians]. / Neurofibromatosis tipo I manifestada como mielopatía cervical progresiva. Primer caso descrito entre los indios Kaxinawa.

INTRODUCTION: Type I neurofibromatosis is an autosomal dominant disorder with an estimated prevalence of 1/3,000. Half of the new cases are due to mutations; their penetration is complete in adults and may affect any ethnic group. We describe the first reported case of type I neurofibromatosis in a Kaxinawa Indian from the state of Acre, Brazil, in whom the presenting symptoms were of progressive tetraparesis due to multiple paraspinal neurofibromata. CLINICAL CASE: A 16 year old indigenous Kaxinawa boy presented with progressive myelopathy for the past six months. On neurological examination he had hyperreflexive spastic tetraparesia, predominantly on the right side, with the sensory level at C3/C4, multiple medullary automatisms and respiratory difficulty. He also had diffuse café-au-lait stains, including one particularly prominent one measuring 15 cm on his right buttock. MR of the spine showed many hypo-intense lesions at T1 and hyperintense lesions at T2, which took up contrast and were present at all the conjugation foramens bilaterally. These lesions originated at the roots and were suggestive of neurofibromata. On mediastinal tomography there were several neurofibromata in the mediastinum. The patient had a surgical operation for spinal decompression, with a laminectomy at C1/C2 and removal of the neurofibromata on the spinal cord at C1 and C2. The patient has a sister with multiple café-au-lait stains. CONCLUSIONS: Because of the traditional isolation of the Kaxinawa Indians, with whom contact was made at the beginning of the twentieth century, this first case reported of type I neurofibromatosis may be due to a new mutation which presented as a florid form of the disease with multiple spinal neurofibromata.

Neurofibromatosis type 1 in Israel: survey of young adults.

Neurofibromatosis type 1 (NF1) (von Recklinghausen's disease) is one of the most common human autosomal dominant disorders. In a survey of 374440 17 year old Jewish recruits for military service, 390 cases of NF1 were discovered, with a prevalence of 1.04/1000 (0.94/1000 for males and 1.19/1000 for females), or two to five times the reported prevalence of this disease. NF1 was more common in youngsters whose parents were of North African and Asian origin (1.81/1000 and 0.95/1000, respectively) and less common in those of European and North American origin (0.64/1000). All these differences were statistically significant and may be partially explained by the more advanced parental age of the NF group (as suggested by the larger number of children in the North African and Asian families) or by founder effect or both. The height and weight of the NF1 subjects was significantly lower than those of the controls. The intelligence score of persons with NF1 was similar to that of the control group when corrected for gender and ethnic origin. No significant increase in epilepsy or mental illnesses was found. This study provides evidence of the high overall prevalence of NF1 among Jews in Israel, with significantly increased prevalence in certain ethnic groups.

Clinical manifestations of neurofibromatosis-1 in Chinese children.

The complications of 50 Chinese children with neurofibromatosis-1 were found to be different from other ethnic groups. There was a predominance of scoliosis, speech problems, and blood malignancies, but brain tumors were rare. The majority had good prognosis. Clinical manifestations depend on the age of ascertainment and, therefore, the prediction of associated complications should be made accordingly.

Somatostatin-producing duodenal carcinoids in patients with von Recklinghausen's neurofibromatosis. A predilection for black patients.

Eight patients with von Recklinghausen's disease (VRD) and duodenal carcinoids are presented. Seven patients were black, and one white. Six of the eight were women. The presenting symptom was either jaundice or abdominal pain. All tumors were located in the second portion of the duodenum, and three were multiple. Associated tumors other than neurofibromas included multiple leiomyomas, meningioma, neurofibrosarcoma, and prostatic sarcoma. Seven tumors had psammoma bodies, and in three they were numerous. Somatostatin-positive cells were demonstrated in all cases. Two tumors had spread to regional lymph nodes at the time of surgery. There appears to be a predilection for black patients among those with VRD and duodenal carcinoids.