HRAS-related epidermal nevus syndromes: Expansion of the spectrum with first branchial arch defects.

Epidermal nevus syndrome (ENS) comprises a heterogeneous group of neurocutaneous syndromes associated with the presence of epidermal nevi and variable extracutaneous manifestations. Postzygotic activating HRAS pathogenic variants were previously identified in nevus sebaceous (NS), keratinocytic epidermal nevus (KEN), and different ENS, including Schimmelpenning-Feuerstein-Mims and cutaneous-skeletal-hypophosphatasia syndrome (CSHS). Skeletal involvement in HRAS-related ENS ranges from localized bone dysplasia in association with KEN to fractures and limb deformities in CSHS. We describe the first association of HRAS-related ENS and auricular atresia, thereby expanding the disease spectrum with first branchial arch defects if affected by the mosaic variant. In addition, this report illustrates the first concurrent presence of verrucous EN, NS, and nevus comedonicus (NC), indicating the possibility of mosaic HRAS variation as an underlying cause of NC. Overall, this report extends the pleiotropy of conditions associated with mosaic pathogenic variants in HRAS affecting ectodermal and mesodermal progenitor cells.

Identification of Codon 146 KRAS Variants in Isolated Epidermal Nevus and Multiple Lesions in Oculoectodermal Syndrome: Confirmation of the Phenotypic Continuum of Mosaic RASopathies.

Mosaic RASopathies are a molecularly heterogeneous group of (neuro)cutaneous syndromes with high phenotypical variability. Postzygotic variants in KRAS have been described in oculoectodermal syndrome (OES), encephalocraniocutaneous lipomatosis (ECCL) and epidermal nevus syndrome (ENS). This study confirms the continuum of mosaic neurocutaneous RASopathies showing codon 146 KRAS variants in an individual with OES and, for the first time, in an individual with (isolated) epidermal nevus. The presence of a nevus psiloliparus in individuals with OES indicates that this finding is not specific for ECCL and highlights the phenotypical overlap between ECCL and OES. The presence of the somatic KRAS variant in the nevus psiloliparus resolves the underlying molecular etiology of this fatty-tissue nevus. In addition, this finding refutes the theory of non-allelic twin-spotting as an underlying hypothesis to explain the concurrent presence of two different mosaicisms in one individual. The identification of codon 146 KRAS variants in isolated epidermal nevus introduces a new hot spot for this condition, which is useful for increasing molecular genetic testing using targeted gene sequencing panels.

The proactive wet-wrap method with diluted corticosteroids versus emollients in children with atopic dermatitis: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Wet-wrap treatment (WWT) has been advocated as a relatively effective treatment in children with severe atopic dermatitis (AD). WWT often serves as crisis intervention for AD. OBJECTIVES: We sought to evaluate the use of WWT with diluted corticosteroids in comparison with emollient in children with severe AD during 4 weeks in a proactive schedule during which the frequency of corticosteroid applications was tapered. METHODS: A randomized, double-blind, placebo-controlled study was performed in children aged 6 months to 10 years with severe AD (objective SCORAD at least 40 ± 5), comparing WWT with diluted corticosteroids (1:3 mometasone furoate 0.1% ointment and for the face 1:19 mometasone furoate 0.1% ointment under a mask) with emollient (petrolatum 20% in cetomacrogol cream). The primary outcome was improvement of the objective SCORAD; secondary outcomes included Patient-Oriented Eczema Measure and quality-of-life index. RESULTS: WWT with diluted corticosteroids acted faster and was more efficacious than WWT with emollients. Best results were obtained in age groups 6 to 9 years and 0 to 3 years. The difference in efficacy evaluated by objective SCORAD was significant at all measuring points. This also applied to the quality-of-life index. LIMITATIONS: The study group was relatively small. CONCLUSIONS: WWT for severe AD is an effective therapy option for at least a period of 4 weeks.