The Spectrum of Epidermolysis Bullosa in KwaZulu-Natal, South Africa.

Abstract

Background: Epidermolysis bullosa (EB) is a rare, heterogeneous genodermatosis characterized by skin fragility due to inherited defects in genes encoding proteins that maintain epidermal-dermal integrity. The severity and complications of EB vary by subtype, and no cure currently exists. The epidemiology is unknown in South Africa.

Methods: This prospective observational study in KwaZulu-Natal correlated African Zulu EB patients' phenotypic features with genotypic and histological findings. Whole-exome sequencing, electron microscopy, and immunofluorescence mapping were used to identify EB subtypes.

Results: Fourteen of the 15 patients recruited initially were confirmed to have EB, while one was excluded due to poor clinicopathological-genetic correlation. Junctional EB (JEB) was identified in 11 patients, with 10 cases linked to a recurrent homozygous pathogenic variant in LAMB3, causing severe JEB, and one to ITGA3 with an unusual variant of interstitial lung disease, nephrotic syndrome, and EB (ILNEB). Two patients had autosomal dominant EB simplex, both with heterozygous KRT14 variants, and one had dominant dystrophic EB associated with a heterozygous COL7A1 variant. Eleven patients presented during the neonatal period, with a mean survival of four weeks, highlighting a high mortality rate, especially in the severe JEB cases. The cohort exhibited a balanced sex distribution, with no clear cases of consanguinity observed.

Conclusion: JEB, with a recurrent pathogenic variant in LAMB3, emerged as the predominant subtype among African Zulu patients, underscoring the critical need for early diagnosis and tailored management strategies in resource-limited settings. Integrating clinicopathological and genetic data is essential for accurate diagnosis and prognosis, emphasizing the importance of advanced diagnostic tools in improving outcomes for EB patients in South Africa.