Epidermal nevus syndromes (ENS) are a group of complex disorders characterized by the presence of epidermal hamartomas in association with extracutaneous manifestations involving numerous organ systems. The diseases included within the spectrum of ENS are quite rare and specific molecular defects have been elucidated in only a few cases. An epidermal nevus syndrome with a mutation of the ZMYM2 gene has not been reported to the best of our knowledge.

This is a case of a 17-year-old female who presented at birth with prominent skeletal deformities and multiple erythematous verrucous papules and plaques in a blaschkoid distribution on the back and extremities, increasing in size and number as the patient grew. The patient was also noted to have delayed gross motor and speech milestones as well as marked mixed hearing loss on both ears. Histologic findings of the skin lesions were consistent with Verrucous Epidermal Nevus. Further imaging workups revealed the presence of bilateral diminutive kidneys. Whole exome sequencing by orthogonal method (Sanger sequencing) was performed revealing a likely pathogenic variant of the ZMYM2 gene, a gene which as of writing, has not been associated with any epidermal nevus syndrome.

We provide the first evidence of the possibility of involvement of the gene ZMYM2 in ENS. Considering the detected variant does not fully explain the patient’s phenotype, proceeding to genome sequencing and performing targeted testing by next generation sequencing on the affected tissue to assess the mosaicism of the detected variant is highly considered.

Human ; Female ; Adolescent: 13-18 Yrs Old

Netherton Syndrome (NS) is characterized by a triad of congenital ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis. Diagnosis of NS poses a challenge due to its variable presentation and overlap with other dermatological conditions. Herein, we report a case of NS in a sibling pair, underscoring the challenges in diagnosis and genetic implications of this condition.

We present a case of an 8-year-old female and a 7-year-old male sibling pair, with Netherton Syndrome, who initially presented with atopic dermatitis and erythroderma without hair shaft abnormalities. Further investigation and genetic testing revealed homogeneous SPINK5 gene mutations in both patients, leading to the diagnosis of NS.

Early recognition and diagnosis of Netherton Syndrome are essential for proper management. In patients with early-onset atopic dermatitis resistant to treatment and recurrent erythroderma, further investigation is needed to exclude other diagnoses like Netherton Syndrome.

Human ; Male ; Female ; Child: 6-12 Yrs Old ; Netherton Syndrome