{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:39:58Z","timestamp":1782401998207,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2006,6,12]],"date-time":"2006-06-12T00:00:00Z","timestamp":1150070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with highly variable expression generally ascribed to random factors. However, evidence is presented for patterns suggesting non\u2010stochastic processes as follows: (1) We have seen a MZ twin pair concordant for renal vascular hypertension, and another for unilateral ptosis. Other concordances have been reported, including both malformations and tumors, and combinations as well. (2) Four children were seen with a distinct ipsilateral association of glaucoma or iris anomaly, optic glioma, plexiform neurofibromas arising from the trigeminal nerve and its branches, and sphenoid dysplasia. Other cases in the literature support milder forms of this association. (3) We saw six children with apparent gynecomastia or premature thelarche without endocrine abnormalities. Tissue samples from four of these showed an unusual fibrous plexiform neurofibroma. Interestingly, five of the six cases were African Americans, and constitutional factors affecting fibrous reactions may also be involved here.<\/jats:p><jats:p>A tentative hypothesis is presented suggesting vascular fields involving defined areas that can: (1) Support tumor growth. They would be the \u201csoil\u201d determining the ability and the extent of growth. There would, however, still be a need for a \u201csecond hit\u201d tumor transformation. (2) Affect blood supply to organs, creating structural anomalies. NF1 involves a vasculopathy, and would predispose to vulnerabilities of such fields. Genetic factors could induce superimposed susceptibilities of specific fields, leading to twin concordances. \u201cHits\u201d affecting specific fields would increase the likelihood of multiple abnormalities that could include both tumors and structural findings. Finally, tumors may follow the contours of existing fields. The breast is an area normally primed for growth, and the observation of clitoromegally secondary to tumor involvement suggests that such fields exist elsewhere. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31303","type":"journal-article","created":{"date-parts":[[2006,6,13]],"date-time":"2006-06-13T03:32:04Z","timestamp":1150169524000},"page":"2080-2084","source":"Crossref","is-referenced-by-count":11,"title":["Non\u2010random associations and vascular fields in neurofibromatosis 1: A pathogenetic hypothesis"],"prefix":"10.1002","volume":"140A","author":[{"given":"Mark S.","family":"Lubinsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,6,12]]},"reference":[{"key":"e_1_2_4_2_1","volume-title":"Hydrophthalmia; or, congenital glaucoma: Its causes, treatment, and outlook","author":"Anderson JR","year":"1939"},{"key":"e_1_2_4_3_1","first-page":"598","article-title":"Neurofibromatosis and agenesis of the corpus callosum in identical twins: MR diagnosis","volume":"9","author":"Atlas SW","year":"1988","journal-title":"Amer J Neuroradiology"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-196210000-00004"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992288202100408"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0266-7681(05)80088-9"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1983.tb13774.x"},{"key":"e_1_2_4_8_1","first-page":"93","article-title":"Primary optic atrophy in von Recklinghausen's disease","volume":"18","author":"Dresner E","year":"1949","journal-title":"Quart J Med"},{"key":"e_1_2_4_9_1","volume-title":"System of ophthalmology. 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