An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation
ABSTRACT A 5-year-old Mexican girl had a bilateral, systematized epidermal nevus of a non-epidermolytic, non-organoid type covering large parts of her body with the exception of the scalp. Clinically, this nevus was of a soft, velvety type showing affinity to the large body folds. Histopathological examination revealed orthohyperkeratosis and papillomatosis without granular degeneration and without any abnormality of adnexal structures. During infancy she developed seizures, and subsequently a delayed mental development was noted. Computer tomography of the brain revealed cortical and subcortical atrophy, a subdural hygroma in the left frontoparietotemporal region, and hypoplasia of corpus callosum. Molecular analysis of a biopsy specimen obtained from the epidermal nevus revealed a heterozygous R248C hotspot mutation in FGFR3, whereas in normal skin the FGFR3 wild-type allele was exclusively found. The R248C mutation was also present in DNA extracted from blood leukocytes. Because FGFR3 is involved in the development of the central nervous system, the clinical and genetic findings of this case indicate a widespread mosaicism of the FGFR3 mutation. This unusual mosaic phenotype may represent a distinct entity within the group of epidermal nevus syndromes.
BMC Medical Genetics 12/2015; 16(1). DOI:10.1186/s12881-015-0146-5 · 2.45 Impact Factor
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ABSTRACT: Seborrheic keratosis (SK) and epidermal nevi (EN) represent benign skin tumors and congenital lesions, respectively. Oncogenic mutations are fundamentally involved in their pathogenesis and SK is characterized by a broad spectrum of somatic mutations in the FGFR3, PIK3CA, RAS, AKT1 and EGFR genes. In contrast to malignant tumors, SK is genetically stable without alterations of tumor suppressor genes. The ENs are caused by postzygotic activating hot spot mutations in FGFR3, PIK3CA and particularly HRAS, resulting in a genetic mosaicism. The size of the lesions and the differentiation potential of the mutated cell into various tissue types depends on the time point of the mutation during embryogenesis. The genetic mosaic may predispose to a later growth of benign and malignant (adnexal) tumors.Der Pathologe 09/2014; 35(5):413-23. DOI:10.1007/s00292-014-1928-9 · 0.64 Impact Factor
Article: Congenital Epidermal Nevus[Show abstract] [Hide abstract]
ABSTRACT: Epidermal nevi are hamartomas that are characterized by hyperplasia of the epidermis and adnexal structures, and may be associated with serious disfiguration. Germline mutations in the FGFR3 gene have found to be the etiology of epidermal nevus. Patients often seek treatment from dermatologic surgeons but even an alert dentist can help to diagnose the lesion from its clinical appearance. Various treatment modalities are available and it is the clinician's choice to choose depending upon the patient's condition. How to cite this article: Arora B, Khinda VIS, Bajaj N, Brar GS. Congenital Epidermal Nevus. Int J Clin Pediatr Dent 2014;7(1): 43-46.04/2014; 7(1):43-6. DOI:10.5005/jp-journals-10005-1232