An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation

Instituto Dermatológico de Jalisco "Dr. José Barba Rubio", Guadalajara, Mexico.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 09/2008; 146A(17):2275-9. DOI: 10.1002/ajmg.a.32429
Source: PubMed


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.

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    • "In addition, these mutated cells do not undergo a form of self-destruction called apoptosis as readily as normal cells. These effects result in overgrowth of skin cells, leading to epidermal nevi.18-10 "
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    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
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    • "Even her slight scoliosis may be part of the syndrome, although the finding could be coincidental and independent from the mosaicism. Hitherto the R248C FGFR3 mutation has been identified in two cases of an EN syndrome: - one with facial dysmorphism, and the other patient with cerebral involvement [21,22]. A preliminary designation of "FGFR3 EN syndrome" has been proposed, while acknowledging that a genetic heterogeneity may underlie the clinical phenotype of this syndrome [1,22]. "
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    ABSTRACT: Epidermal nevi (EN) represent benign congenital skin lesions following the lines of Blaschko. They result from genetic mosaicism, and activating FGFR3 and PIK3CA mutations have been implicated. We report a female patient with a systemic keratinocytic nevus also involving the oral mucosa. Molecular genetic analysis revealed a mosaicism of the FGFR3 hotspot mutation R248C in the EN lesions of the skin and of the oral mucosa. The detection of the R248C mutation in a proportion of blood leukocytes and a slight scoliosis suggest an EN syndrome. Our results show that activating FGFR3 mutations can also affect the oral mucosa and that extracutaneous manifestations of EN syndrome can be subtle. We highlight the theoretical risk of the patient having an offspring with thanatophoric dysplasia as gonadal mosaicism for the R248C mutation cannot be excluded.
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