Epidermolysis bullosa (EB) is a genodermatosis that encompasses a group of clinically and genetically heterogeneous disorders classified in four major types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome. Our aim was to characterize recurrent and novel mutations associated to EB in a sample of Brazilian patients. Eighty‐seven patients (25 EBS, 4 JEB and 58 DEB) were studied. We performed a next‐generation sequencing‐based multigene panel through ion torrent technology including 11 genes: KRT5, KRT14, PLEC, TGM5, LAMA3, LAMB3, LAMC2, COL17A1, ITGB4, COL7A1, and FERMT1. A total of 72 different pathogenic or likely pathogenic variants were identified, 32 of them are novel. The causal variant was detected in 82 patients (efficiency of 94.3%). Pathogenic variants in the residue 125 of KRT14 were identified in 32% of all EBS patients. In DEB patients, four COL7A1 variants were quite frequent, some of them clustered in specific Brazilian regions. Our study extends the spectrum of known mutations in EB and describes, for the first time, the genetic profile of EB patients from Brazil.

Congenital absence of skin (CAS) is a clinical sign associated with the main types of epidermolysis bullosa (EB). Very few studies have investigated the genetic background that may influence the occurrence of this condition. Our objective was to investigate genotype-phenotype correlations on EB with CAS through a literature revision on the pathogenic variants previously reported. A total of 171 cases (49 EB simplex, EBS; 23 junctional EB, JEB; and 99 dystrophic EB, DEB), associated with 132 pathogenic variants in eight genes, were included in the genotype-phenotype analysis. In EBS, CAS showed to be a recurrent clinical sign in EBS with pyloric atresia (PA) and EBS associated with kelch-like protein 24; CAS was also described in patients with keratins 5/14 alterations, particularly involving severe phenotypes. In JEB, this is a common clinical sign in JEB with PA associated with premature termination codon variants and/or amino acid substitutions located in the extracellular domain of integrin α6β4 genes. In DEB with CAS, missense variants occurring close to non-collagenous interruptions of the triple-helix domain of collagen VII appear to influence this condition. This study is the largest review of patients with EB and CAS and expands the spectrum of known variants on this phenomenon.

Background Epidermolysis bullosa is characterized by cutaneous fragility and blistering. Historically, diagnosis is achieved by immunofluorescence mapping or transmission electron microscopy, both involving biopsy procedures. Genetic analysis, especially through next-generation sequencing, is an important tool for the diagnosis of this disease. In Brazil, access to diagnostic methods is limited, and consequently, most patients do not have an accurate diagnosis. Diagnosis allows the indication of prognosis and genetic counselling of the patient. Objectives To evaluate the cost-effectiveness of a gene panel compared to immunofluorescence mapping and transmission electron microscopy by analyzing its benefits, limitations, and economic aspects. Methods The gene panel included the 11 main genes associated with epidermolysis bullosa. The techniques were compared, assessing the average cost, advantages, and limitations, through a price survey and literature review. Results Both immunofluorescence mapping and transmission electron microscopy require skin biopsy, are dependent on the investigator’s expertise, and are subject to frequent inconclusive results. The gene panel is effective for the conclusive diagnosis of epidermolysis bullosa, presents high efficiency and accuracy, is economically feasible, and excludes the need for biopsy. The gene panel allows for prognosis, prenatal genetic diagnosis, and genetic counseling. Study limitations It was not possible to find laboratories that perform transmission electron microscopy for epidermolysis bullosa diagnosis in Brazil. Conclusion This study supports the gene panel as the first-choice method for epidermolysis bullosa diagnosis.

We report the case of an infant with Adams-Oliver syndrome, a rare disorder characterized by aplasia cutis congenita, defects of the limbs and extremities, and cutis marmorata telangiectatica. Other associated anomalies have been reported, such as facial dysmorphism, heart defects, and disorders of the central nervous system.