Pediatrics 2027

Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosiform dermatoses which primarily affects the skin characterized by a profound thickening of the keratin layer in fetal skin which is associated with the adenosine triphosphate (ATP) – binding cassette subfamily A member 12 (ABCA12) gene mutation. This is a case of a full-term neonate with clinical features of harlequin ichthyosis noted at birth described as plate-like configuration separated by fissures with associated ectropion, eclabium, and underdeveloped hands and feet. Skin punch biopsy was facilitated which showed massive hyperkeratosis in the stratum corneum of epidermis which was consistent with harlequin ichthyosis. Invitae Congenital Ichthyosis Panel, which includes testing of ABCA12 gene associated with autosomal recessive congenital ichthyosis, was performed. Data analysis showed one pathogenic variant, c.1210C>T (p.Arg404*) which was concluded to be a new variant and another of uncertain significance, c.7405T>C (p.Cys2469Arg) which was later on reclassified as likely pathogenic, associated with autosomal recessive congenital ichthyosis. Further parental studies showed one likely pathogenic variant, c.7405T>C (p.Cys2469Arg) from the paternal sample and a pathogenic variant, c.1210C>T (p.Arg404*), was detected from the maternal sample resulting in the trait being inherited by the patient. Genetic evaluation has mapped an autosomal recessive mutation in the ABCA12 gene with the probable implication that ABCA12, Exon 11, c.1210C>T (p.Arg404*) sequence change creates a premature translational stop signal (p.Arg404*) in the ABCA12 gene that is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA12 are known to be pathogenic and this variant is not currently present in population databases. In addition, this has not been reported in the literature in individuals with ABCA12-related conditions. For these reasons, it has been classified as a new variant and pathogenic. Because of the disease's rarity, no information on its racial and gender predisposition is available.

Adrienne C. Ang is a Diplomate of the Philippine Pediatric Society with a background in pharmacy and medicine, earning her BS in Pharmacy in 2014 and medical degree in 2019. She currently serves as a Medical Officer at Mangatarem District Hospital under a Department of Health deployment program and has completed residency training in General Pediatrics at Region I Medical Center. Her case report on a novel pathogenic variant in a rare case of Harlequin ichthyosis was presented at the 18th APCP Research and Scientific Exhibit Committee in Cebu and selected for digital poster presentation at the European Congress of Perinatal Medicine, both in September 2024.