Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder with wide clinical heterogeneity, ranging from localized skin fragility to life-limiting systemic complications. Understanding genotype-phenotype correlations in COL7A1, the causative gene, is critical for clinical prognostication, genetic counseling, and the rational design of emerging molecular therapies. To determine the frequency of genotypic and phenotypic subtypes, and to assess whether variant type or location can predict phenotypic severity and extracutaneous complications in patients with RDEB carrying homozygous variants. This was a systematic review of all RDEB genotypes and phenotypes reported to the International Dystrophic Epidermolysis Bullosa Patient Registry (DEB Registry) and eligible studies published in English from May 1993 to September 2025. PubMed, Cochrane Library, and Web of Science were searched and eligible studies were reviewed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020) guidelines. Included studies reported bi-allelic COL7A1 variants and clinical phenotypes. Data from the DEB Registry were cross-checked to supplement the published cases. Descriptive statistics were used for data analyses, and Fisher exact and χ2 methods were used to test additional genotype-phenotype correlations in patients with RDEB carrying homozygous variants. A total of 1802 patients with RDEB comprising 1002 pathogenic variants within COL7A1 were identified from 217 articles. Among the 706 patients with homozygous variants (mean [SD; range] age, 12.2 [13.0; 0-72] years), 533 (75.5%) had severe RDEB, most frequently associated with frameshift and nonsense variants (388 [72.8%] premature termination codons [PTCs]). In contrast, intermediate and milder subtypes were associated with missense or non-PTC variants. Variant location also influenced phenotype: homozygous variants affecting the noncollagenous 1 domain were associated with severe RDEB in 74 of 83 unique variants (89.2%). Extracutaneous involvement clustered in homozygous PTC carriers and was observed almost exclusively in severe RDEB, with occasional cases in the intermediate subtype and rare instances in the inversa, localized, and self-improving subtypes. Recurrent and population-specific variants suggested founder effects. Splice site and missense variants showed phenotypic variability, with augmented intelligence-based predictions correlating with severity. In this systematic review, the type and site of pathogenic variants in COL7A1 correlated with the severity of RDEB phenotype across different nationalities, races, and ethnicities. These findings may provide improved patient prognosis, genetic counseling, and personalized therapeutics.

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

Epidermolysis bullosa (EB) comprises a heterogeneous group of skin fragility disorders, classified in four major types based on skin cleavage level, i.e. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, and in more than 30 subtypes defined by the combination of laboratory and clinical data, including disease course. Our aims were to address whether, in the age of genomics, electron microscopy (TEM) has still a role in diagnosing EB, and whether the genotype per se may be sufficient to sub-classify EB. A thoroughly characterized single-centre EB case series was retrospectively evaluated to compare the power of TEM with immunofluorescence mapping (IFM) in establishing the EB type, and the ability of TEM, IFM and genetics to predict selected EB subtypes, i.e. severe dominant EBS (DEBS), severe JEB, severe recessive DEB (RDEB) and DEB self-improving, using genetic and final diagnosis, respectively, as gold standard. The series consisted of 87 patients, including 44 newborns, with a median follow-up of 54 months. Ninety-five mutations were identified in EB-associated genes, including 25 novel variants. Both IFM and TEM were diagnostic in about all cases of JEB (21/21 for both) and DEB (43/44 for IFM, 44/44 for TEM). TEM sensitivity was superior to IFM for EBS (19/20 vs. 16/19). As to EB subtyping, IFM performed better than genetics in identifying severe JEB cases due to laminin-332 defect (14/14 vs. 10/14) and severe RDEB (eight/nine vs. seven/nine). Genetics had no role in self-improving DEB diagnosis; it almost equalled TEM in predicting severe DEBS (eight/nine vs. nine/nine) and enabled to discriminate dominant from recessive non-severe DEB phenotypes and to identify special subtypes, e.g. DEBS with KLHL24 mutations. Transmission electron microscopy remains relevant to the diagnosis of EBS. IFM and genetics are essential and complementary tools in the vast majority of EB cases.

Self-improving dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by significant improvement in skin fragility within the first few years of life. Genetic inheritance has previously been reported as autosomal dominant or recessive with both forms harboring mutations in COL7A1. To date, there have been no reports of this rare clinical entity from various Southeast Asian ethnicities. Here, we describe the clinical and molecular features of five patients from the Southeast Asia region who presented with predominantly acral-distributed blisters and erosions in the first few days of life. Blistering resolved over several months, without appearance of new blisters. By immunofluorescence, intraepidermal retention of Type VII collagen was observed in all patient skin biopsies when investigated with antibody staining. Genetic analysis of four patients revealed pathogenic variants in COL7A1 which have not been previously reported. The clinical diagnosis in these rare patients is confirmed with molecular histology and genetic characterization.