P2A297: Infant with a Hereditary Blistering Disorder, an Interesting Case in the NICU

Introduction: Inherited blistering disorders, including Epidermolysis Bullosa (EB) is a rare group of genetic skin blistering disorders affecting the underlying structural proteins. This is a lifelong condition requiring consistent and dedicated care to prevent further complications. As such, the burden on caregivers is significant enough to warrant a standard of care. There are available recommendations for the management of these disorders, but currently no gold standard of acute symptomatic treatment exists, as the disease management is actively under investigation with a focus on gene targets [2, 3]. The goal of this case report is to give a detailed account of a hereditary blistering disorder with genetic variant of unknown significance (VUS) and provide management recommendations which could be applied to similar cases and settings in the newborn period.

Case Description: Full term female with reported family history of EB, developed skin blisters (Figure 1) on the first day of life (DOL) without mucosal or ocular involvement. Multidisciplinary approach was taken to prevent worsening skin blistering and associated complications. The patient was placed on a rigorous wound care regimen with topical antibiotics, two layers of emollients, gauze, and z-flo mattress. On DOL 7, infant was discharged home without blisters (figure 2) with close dermatology and genetic follow up. Genetic testing revealed variants of unknown significance (VUS) in two genes: KRT1 c. 1012T>C (p.S338P) (autosomal dominant inheritance) and PLEC c.7269G>A (p.Q2423=) (autosomal recessive or dominant inheritance). The patient is heterozygous for both variants. The KRT1 variant was determined to be maternally inherited from a parent with history of skin blistering and hyperkeratosis. To the best of our knowledge, these variants are new and will provide an opportunity to further explore their clinical implications.

Discussion: Multidisciplinary care including dermatology, wound care, and occupational therapy, lead to full recovery in our patient within six days of life. Although these results are encouraging, more studies are needed to establish a standard of care for acute skin blistering disorder management. Home care instructions are needed for caregivers in order to prevent skin trauma and lifelong complications.

Conclusion: From a genetics perspective, pathogenic variants in the KRT1 gene are typically associated with epidermolytic ichthyosis; a condition which presents at birth with erythroderma, blisters, large areas of denuded skin and subsequent hyperkeratosis [3]. This variant is classified as a VUS by the laboratory based on the American College of Medical Genetics (ACMG) variant classification criteria; however, inheritance from a symptomatic family member and a previously published case report increase suspicion that this is a disease-causing variant (4, 5). Further investigation into the segregation of the KRT1 variant within this family may help provide additional information to reassess the clinical significance of the patient’s genetic findings.