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

• Published in: American journal of medical genetics. Part A 2008-09, Vol.146A (17), p.2275-2279
• Main Authors: García‐Vargas, Alejandro, Hafner, Christian, Pérez‐Rodríguez, Adriana G., Rodríguez‐Rojas, L. Ximena, González‐Esqueda, Pedro, Stoehr, Robert, Hernández‐Torres, Mercedes, Happle, Rudolf
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Adult and adolescent clinical studies; Biological and medical sciences; Cerebrum - abnormalities; Child, Preschool; CNS defects; Dermatology; epidermal nevus syndromes; Epidermis - abnormalities; Epilepsy - genetics; epileptic seizures; Female; FGFR3 mutation; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Intellectual deficiency; Intellectual Disability - genetics; Medical genetics; Medical sciences; mental retardation; Mosaicism; Mutation; Nervous system (semeiology, syndromes); Neurology; Nevus, Pigmented - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Skin Neoplasms - genetics; Syndrome; systematized non‐organoid, non‐epidermolytic epidermal nevus; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32429

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. © 2008 Wiley‐Liss, Inc.