Mosaic KRAS mutation in a patient with encephalocraniocutaneous lipomatosis and renovascular hypertension

Somatic KRAS mutation affecting codon 146 in linear sebaceous nevus syndrome

“…McDonell et al, 2018) further lending credibility to the concept that LSNS, ECCL and OES are part of the same spectrum of mosaic RASopathies.Merging these entities has clinical implications. A thorough neurological examination should be pursued for any child presenting with a scalp nevus, especially when other anomalies like corneal dermoids or choroidal osteomas are noted.…”

Novel findings and expansion of phenotype in a mosaic RASopathy caused by somatic KRAS variants

“…Mosaic variants in KRAS have been described in multiple conditions with increasingly recognized overlapping features, as recently summarized by Boppudi et al (2016). These include the Schimmelpenning syndrome (Groesser et al, 2012;Mitchell et al, 2019;Nagatsuma et al, 2019), oculo-ectodermal syndrome (OES) (Boppudi et al, 2016;Peacock et al, 2015), encephalocraniocutaneous lipomatosis (ECCL) (Boppudi et al, 2016;McDonell et al, 2018), autoimmune lymphoproliferative syndrome (OMIM 614470) (Takagi et al, 2011), nevus sebaceous (Groesser et al, 2012;Levinsohn et al, 2013;Lihua et al, 2017;Wang et al, 2015) and epidermal nevus (OMIM 162900) (Bourdeaut et al, 2010;Farschtschi et al, 2015;Igawa et al, 2016), phacomatosis pigmentokeratotica (PPK) (Om et al, 2017), low-flow vascular malformations and AVMs (OMIM 108010) (Al-Olabi et al, 2018;Goss et al, 2019;Oka et al, 2019;Ten Broek et al, 2019), and melorheostosis (OMIM 155950) (Whyte et al, 2017). The spectrum of phenotypes likely reflects the individual KRAS variant effects (including those of recurrent dominant hotspots), location, and timing of the genetic change.…”

“…Two individuals (patients 1 and 2) had bony cortical lesions which appear similar to the findings of melorheostosis (mono-or polyostotic osteosclerosis and hyperostosis) described by Whyte et al (2017) in a patient with a large epidermal nevus and a leg length discrepancy, found to have a mosaic KRAS p.Gln61His pathogenic variant. Lytic lesions with features of giant cell-rich benign tumors or nonossifying fibromas have been described in patients with mosaic KRAS variants diagnosed with OES (Boppudi et al, 2016;Peacock et al, 2015) and ECCL (Delfino et al, 2011;McDonell et al, 2018). There is limited information regarding the evaluations and natural history of these lesions.…”

Parkes Weber syndrome with lymphedema caused by a somatic KRAS variant

“…Somatic variants in KRAS also have been associated with encephalocraniocutaneous lipomatosis and Schimmelpenning syndrome (Groesser et al, 2012;McDonell et al, 2018). Patients with Schimmelpenning syndrome have an increased risk of vascular anomalies, including lymphatic malformations (Greene, Rogers, & Mulliken, 2007).…”