Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene

Segmental neurofibromatosis (NF) is generally thought to result from a postzygotic NF1 (neurofibromatosis type 1) gene mutation. However, this has not yet been demonstrated at the molecular level. Using fluorescence in situ hybridisation (FISH) we identified an NF1 microdeletion in a patient with segmental NF in whom café-au-lait spots and freckles are limited to a single body region. The mutant allele was present in a mosaic pattern in cultured fibroblasts from a café-au-lait spot lesion, but was absent in fibroblasts from normal skin as well as in peripheral blood leukocytes. These findings prove the hypothesis that the molecular basis of segmental cutaneous NF is a mutation in the NF1 gene and that the regional distribution of manifestations reflects different cell clones, commensurate with the concept of somatic mosaicism.     

Early childhood diagnosis of acoustic neuromas in presymptomatic individuals at risk for neurofibromatosis 2

We report on a family in which individuals at risk for NF 2 were investigated with the use of gadolinium-enhanced MRI. This technique has allowed the diagnosis of small ( < 8 mm) acoustic neuromas in two asymptomatic children (age 7 and 11), one of whom had normal audiometric and brainstem-evoked response testing. To our knowledge these are the youngest asymptomatic patients in whom the diagnosis of NF 2 has been demonstrated. It is possible that acoustic neuromas develop at an early age more commonly than recognized previously. The early diagnosis of acoustic neuromas with the use of gadolinium-enhanced MRI may lead to better outcome following surgery. This technique will provide the opportunity to better determine the natural course of this disease.     

Early childhood diagnosis of acoustic neuromas in presymptomatic individuals at risk for neurofibromatosis 2.

We report on a family in which individuals at risk for NF 2 were investigated with the use of gadolinium-enhanced MRI. This technique has allowed the diagnosis of small (less than 8 mm) acoustic neuromas in two asymptomatic children (age 7 and 11), one of whom had normal audiometric and brainstem-evoked response testing. To our knowledge these are the youngest asymptomatic patients in whom the diagnosis of NF 2 has been demonstrated. It is possible that acoustic neuromas develop at an early age more commonly than recognized previously. The early diagnosis of acoustic neuromas with the use of gadolinium-enhanced MRI may lead to better outcome following surgery. This technique will provide the opportunity to better determine the natural course of this disease.     

Clitoromegaly in neurofibromatosis

Genitourinary neurofibromas are rare and clitoral involvement in neurofibromatosis (NF) has been reported infrequently. However, when it occurs, clitoromegaly is often the presenting sign. In many cases, it is congenital. In 236 families with type 1 neurofibromatosis (NF-1) evaluated through the USF Regional Genetics Program between January 1982 and September 1993, four patients had clitoral involvement. In three, involvement was limited to the clitoris. Biopsy/surgical excision in two of them showed a neurofibroma in one and non-specific hamartomatous soft tissue overgrowth in the other. In the fourth patient, the involvement was asymmetric and extended to the labia majora and mons pubis. Endocrine studies and chromosomes in all patients were normal; there was no exposure to androgens, progestins, or coumadin. There was no gestational history of maternal luteomas. Review of the literature documented 26 patients with NF and clitoral involvement. Clitoral involvement in NF-1 appears to be more common than previously reported and the differential diagnosis of ambiguous genitalia should include clitoromegaly due to NF. Pathogenesis of clitoral lesions appears similar to other lesions of NF. Biopsy of such lesions appears to be justified only when malignancy is suspected. © 1995 Wiley-Liss, Inc.     

Dermatoglyphics in von Recklinghausen neurofibromatosis

We studied dermatoglyphic traits in 27 patients (12 males and 15 females) with neurofibromatosis type I (NF-1) to verify which characteristics may be considered typical of this disorder. The frequency of digital central pockets in the patients was significantly greater than in control individuals (P less than .005), but when we evaluated the sexes separately, the difference was significant only among females (P less than .002). The distribution of central pockets on the various fingers was significantly different in affected females, compared with normal controls, but only on fingers II (P less than .05), IV (P .002), and V (P less than .05). The quantitative finger tip pattern values and the total finger ridge count (TFRC) were always higher in the patients, as well as was the a-b ridge count. The latter was significantly increased only on the right hand in females (P less than .01). Among the patients, the atd angle values were increased on both hands of females and on the right hand in males, whereas both the ulnar index A'-d and the a-t' ridge counts were diminished. The frequency of high endings (5' or 5") of line A was increased in NF-1 patients on both hands. Like in previous investigations, our patients showed an increased number of secondary creases, limited to II degree according to Vormittag et al. [1986] (P less than .048). Our results only partially confirmed prior data. Therefore, we think that there is no typical dermatoglyphic pattern in NF-1 and that this parameter is not a diagnostic indicator in this disorder.     

Intrasellar cavernous angioma in neurofibromatosis

A case of neurofibromatosis complicated by a large intrasellar (pituitary) cavernous angioma is reported. Vascular abnormalities, consisting of smooth muscle cell proliferation in the intima of the intermediate and small arteries, were also observed in branches of the renal and pulmonary arteries. An association between neurofibromatosis and intracranial cavernous angioma is discussed.     

COVID-19 in people with neurofibromatosis 1, neurofibromatosis 2, or schwannomatosis

PurposePeople with pre-existing conditions may be more susceptible to severe COVID-19 when infected by SARS-CoV-2. The relative risk and severity of SARS-CoV-2 infection in people with rare diseases such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) is unknown.MethodsWe investigated the proportions of people with NF1, NF2, or SWN in the National COVID Cohort Collaborative (N3C) electronic health record data set who had a positive test result for SARS-CoV-2 or COVID-19.ResultsThe cohort sizes in N3C were 2501 (NF1), 665 (NF2), and 762 (SWN). We compared these with N3C cohorts of patients with other rare diseases (98-9844 individuals) and the general non-NF population of 5.6 million. The site- and age-adjusted proportion of people with NF1, NF2, or SWN who had a positive test result for SARS-CoV-2 or COVID-19 (collectively termed positive cases) was not significantly higher than in individuals without NF or other selected rare diseases. There were no severe outcomes reported in the NF2 or SWN cohorts. The proportion of patients experiencing severe outcomes was no greater for people with NF1 than in cohorts with other rare diseases or the general population.ConclusionHaving NF1, NF2, or SWN does not appear to increase the risk of being SARS-CoV-2 positive or of being a patient with COVID-19 or of developing severe complications from SARS-CoV-2.     

Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis,central neurofibromatosis,NF2, neurofibromatosis type II]

Neurofibromatosis 2 is a dominantly inherited tumor predisposition syndrome caused by mutations in the NF2 gene on chromosome 22. Affected individuals inevitably develop schwannomas typically affecting both vestibular nerves leading to deafness. Rehabilitation with brainstem implants is improving this outcome. Schwannomas also occur on other cranial nerves, on spinal nerve roots, and on peripheral nerves. Meningiomas and ependymomas are other tumor features. In excess of 50% of patients represent new mutations and as many as one third are mosaic for the underlying disease causing mutation. Although truncating mutations (nonsense and frameshifts) are the most frequent germline event and cause the most severe disease, single and multiple exon deletions are common. A strategy for detection of the latter is vital for a sensitive analysis. NF2 represents a difficult management problem with most patients facing substantial morbidity and reduced life expectancy. Surgery remains the focus of current management, although watchful waiting and occasionally radiation treatment have a role. In the future, the development of tailored drug therapies aimed at the genetic level are likely to provide huge improvements for this devastating, life limiting condition.     

Segmental glomerulonephritis.

The renal biopsy findings in 40 patients with segmental glomerulonephritis are reported. The term is used to describe a condition in which one or more segments of the glomerular tuft is involved by disease when other segments appear unaffected on light microscopy. The word 'focal' is not used as it may be taken to imply that the changes affect some glomeruli but not others and the evidence for this is not convincing. Segmental glomerulonephritis was a relatively common finding in cases of proteinuria with or without the nephrotic syndrome. The severity of the glomerular changes did not correlate with the ultimate prognosis. On the other hand the tubular and interstitial changes, as assessed by a grading procedure and by point counting, were significantly less severe in those patients who showed clinical recovery than in those who did not.