Independent NF1 mutations underlie café-au-lait macule development in a woman with segmental NF1

Segmental Neurofibromatosis

“…2,3 It is hypothesized to occur due to a postzygotic mutation of the NF1 gene late in the course of embryonic development affecting a subset of cells (localized neural crest lines) in the fetus rather than a germline NF1 gene mutation that would affect all cells in the body. 4 As a consequence, the disease is localized (i.e., segmental) and further these mutations are detected only in cells in the affected region and not elsewhere in the body or in leucocytes in circulating blood as in most cases of NF. 4,5 SNF was initially classified as NF type V and was considered to have the following characteristics, skin changes or neurofibromas in a single, unilateral body part with no crossing of the midline and absence of family history and systemic involvement.…”

“…4 As a consequence, the disease is localized (i.e., segmental) and further these mutations are detected only in cells in the affected region and not elsewhere in the body or in leucocytes in circulating blood as in most cases of NF. 4,5 SNF was initially classified as NF type V and was considered to have the following characteristics, skin changes or neurofibromas in a single, unilateral body part with no crossing of the midline and absence of family history and systemic involvement. 3,6 However, rarely bilateral SNF has been noted (6% cases) 2,3 and patients with SNF have had children with systemic NF as well.…”

Phacomatoses, genetic testing for personalisation of clinical management (part 1.)

“…Most often, this form results from the appearance of the de novo mutation during embryogenesis (mosaicism) and usually does not affect germ cells (no risk of transmission of the disease). This disease is very difficult to diagnose [27].…”

Large, linear pigmentation anomaly: an unusual dyspigmentation case

“…When CALMs are segmental in nature, an important entity in the differential diagnosis to consider is segmental neurofibromatosis (SNF; type V). Segmental neurofibromatosis is a rare form of neurofibromatosis (NF) in which the classic signs of NF such as neurofibromas, freckling, and CALMs appear in a restricted, mosaic distribution related to a late mutation in the NF1 gene during embryogenesis [3,4]. Prevalence of SNF is approximately 0.0014-0.002% [5].…”