Somatic KRAS mutation affecting codon 146 in linear sebaceous nevus syndrome

Abstract

Linear Sebaceous Nevus Syndrome is a rare disorder that presents with nevus sebaceus in association with corneal dermoids, colobomas, choroidal osteomas, and arachnoid cysts. It is thought to represent a mosaic RASopathy. These are disorders characterized by postzygotic somatic mutation in genes involved in RAS/MAPK signaling pathway. In this report we describe two patients with linear sebaceous nevus syndrome found to have mutations in codon 146 of KRAS with evidence of mosaicism. This specific mutation has previously been reported in Oculoectodermal Syndrome and Encephalocraniocutaneous Lipomatosis, two other mosaic RASopathies with predominantly cerebrooculocutaneous manifestations. These findings suggest that, while initially classified as different syndromes, these disorders should be evaluated and managed as a spectrum of related disorders.

Clinicopathological profile of sclerosing polycystic adenoma/adenosis: A systematic review

“…6,10 It is important to point out that mutations such as PIK3CA, KRAS, and PTEN can be found in non-neoplastic conditions. [30][31][32] Alterations in the KRAS and PTEN were reported in syndromes-related hamartomatous development. 30,31 Recently, mutations in the PIK3CA and KRAS were related to a subset of vascular malformations.…”

“…[30][31][32] Alterations in the KRAS and PTEN were reported in syndromes-related hamartomatous development. 30,31 Recently, mutations in the PIK3CA and KRAS were related to a subset of vascular malformations. 32,33 While PTEN alterations were associated with neurological diseases, 30 showing that the wide clinical spectrum of PIK3CA, KRAS, and PTEN expression may be not often associated with neoplastic development.…”

Nevus Sebaceous Syndrome: A Case Report and Literature Review of the Associated Neurological Complications

“…[28], Salman et al [29]. "Other" includes neurofibroma associated with the nevus [32], severe quadriplegia [17], plagiocephaly [33], asymmetry of spontaneous movements (no diagnosis provided) [28], hearing loss [34], hypoglossal palsy [34], and diffuse hypotonia [31]. Please note that in these cases, the authors did not provide a specific diagnosis beyond ENS.…”

“…Importantly, the earlier in embryogenesis they occur, the more widespread the nevus and the greater the chance (and more extensive and severe) of extracutaneous anomalies. Among patients diagnosed with NSS (which we consider identical to LNSS), HRAS mutations were the most common, including G13R [34,35,[48][49][50][51], G12C [25], G12S [26], and G13V [23], as were KRAS mutations, specifically G12D [14,22,24,25,26,27,30], G12V [28], G12C [20,53], and A146T [31]. One NRAS mutation (Q61R) was found, marking the first causative NRAS mutation in NSS [5], as well as unique mutations such as in the PRKRIR gene (A1674T, R558S) for one patient, and a mutation in the RRP7A gene (C670T, R224W) in another [27].…”