Cerebriform sebaceous nevus: a subtype of organoid nevus due to specific postzygotic FGFR2 mutations

Abstract

Background Postzygotic mutations in FGFR2 have been identified in mosaic forms of acne, keratinocytic epidermal nevi, nevoid acanthosis nigricans / rounded and velvety epidermal nevus and in two fetuses with papillomatous pedunculated sebaceous nevus (PPSN). Objectives To determine the clinical and genetic characteristics of children with cerebriform, papillomatous and pedunculated variants of sebaceous nevi. Methods Infants diagnosed with sebaceous nevi characterized by a cerebriform, papillomatous and/or pedunculated morphology over a 10‐year period (2010–2019) at three paediatric dermatology centres in Switzerland and France were included in this case series. Clinical and histological characteristics were assessed. Next‐generation sequencing was used to assess for FGFR2 mutations. Results All nevi were located on the head, with a rounded or linear shape and a typical cerebriform, sometimes papillomatous and pedunculated, surface. No associated extracutaneous anomalies were found. Nevi harboured postzygotic mutations in the transmembrane domain of FGFR2 in 6/8 children (75%), either the known specific p.(Cys382Arg) mutation in 5 cases, or a novel mutation, p.(Val395Asp), in one. Conclusions We found an exquisite genotype–phenotype correlation in these rare nevi, with specific postzygotic mutations in the transmembrane domain of FGFR2. As not all lesions were truly papillomatous and pedunculated, the term cerebriform sebaceous nevus (CSN) appears more suitable than PPSN to describe this entity. The cerebriform pattern of CSN is reminiscent of cutis gyrata, as seen in Beare–Stevenson syndrome, which is caused by closely related germline FGFR2 mutations. While clinically impressive, CSN seem to carry a good prognosis and a low risk for extracutaneous associations.

Report of a case of RAVEN, hair heterochromia and autism in the setting of FGFR2 mutation

“…In addition, the same mutation has been identified in 5 cases of cerebriform sebaceous nevus on the scalp and none of these children had neurological issues. 5 We found no other cases of RAVEN associated with autism, although it has been suggested that neuronal growth regulator 1 and FGFR2 cooperatively regulate cortical development and core behaviors related to autism in mice. 6 In conclusion, we present a case of RAVEN caused by a heterozygous mutation in FGFR2.The role of the FGFR2 mutation in autism should be further evaluated in this patient.…”

“…Tanaka 4 et al presented a case of congenital extensive linear keratinocytic epidermal nevi of the trunk and acral skin caused by a somatic FGFR2 p.Cys382Arg mutation, the same mutation identified in our patient. In addition, the same mutation has been identified in five cases of cerebriform sebaceous nevus on the scalp and none of these children had neurological issues 5 …”

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

“…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]. Theiler et al [6], examined cerebriform, papillomatous, and/or pedunculated sebaceous nevi from eight pediatric patients. In six of eight nevi, a mutation was found in the FGFR2 transmembrane domain mutation (either C382R or V395D) [6].…”

“…Theiler et al [6], examined cerebriform, papillomatous, and/or pedunculated sebaceous nevi from eight pediatric patients. In six of eight nevi, a mutation was found in the FGFR2 transmembrane domain mutation (either C382R or V395D) [6]. For a patient with FGFR3-ENS (Garcia-Hafner-Happle syndrome), two FGFR3 mutations were identified -R248C [7] and S249C [42].…”

Nevus Sebaceus Arising Within a Scalp Whorl of a Healthy Male Neonate

“…NS is susceptible to hormone-mediated changes during puberty and can develop secondary neoplasms in adulthood. Management for NS has evolved over the years, now typically favoring clinical observation in infancy and early childhood, followed by complete excision during adolescence before puberty [1][2][3][4][5][6][7]. If multiple lesions are present and/or a single lesion is very large in size, NS may be associated with certain syndromes, such as Schimmelpenning syndrome or phakomatosis pigmentokeratotica, both of which can present with extracutaneous defects [5].…”