Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the \"snowflake sign\", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible.

Epidermolysis bullosa (EB) is a group of skin disorders with skin fragility characterized by blistering from minimal mechanical trauma with rupture at the dermoepidermal junction. There are four major classical heritable EB types, due to mutations in as many as 20 distinct genes: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB). This study is aimed at reporting case series on patients (N = 8; males, n = 5 and females, n = 3, age range 12-68 years) affected by EB and performs a review of the literature on this topic. This group of disorders can affect oral soft and hard tissues in various ways, resulting in various effects including enamel hypoplasia, dental caries, microstomia, ankyloglossia, oral blistering, and ulcerations early-onset periodontal disease. From the sample results, it can be concluded that the clinical manifestation of EB patients is highly variable and very different in prognosis. Oral health deeply influences the quality of life of EB patients. Dental management is essential to prevent the aggravation of soft tissue damage and tooth loss and to improve the quality of life through prosthetic and restorative therapies. Dentists should consider the oral alterations of EB subtypes to perform a personalized approach to the patients\' needs in a preventive and therapeutic point of view.

OBJECTIVE: Laryngo-onycho-cutaneous syndrome (LOC) is a rare subtype of junctional epidermolysis bullosa (JEB), featuring aberrant granulation tissue formation in the skin, larynx, and eyes. So far, three mutations including the specific (founder) mutation in exon 39 of LAMA3 (c.151dup) have been identified, but sparse data exists regarding the natural history, the genotype-phenotype correlation, and its differentiation from other JEB types.
METHODS: We reviewed our pediatric EB database to identify English children with clinical and genetically diagnosed LOC within the last 15 years. Their demographic, clinical, and laboratory data were examined. We searched three databases for case reports of LOC between January 1986 and November 2020 and extracted clinical and molecular details.
RESULTS: We identified 6 LOC patients, all female (mean age 5.4 years). Periungual hypergranulation and skin fragility were the earliest presenting signs (0-3 months), followed by laryngeal stenosis, symblepharon (mean onset 10.7 and 11.8 months, respectively), and dental abnormalities. Five children developed anemia at an average of 19.2 months. We identified 22 published studies in English with 31 cases.
CONCLUSIONS: This study delineates the disease course of LOC and highlights the overlap with some forms of JEB. Classical signs/symptoms including anemia appear early in life. Genetic analysis revealed three new LOC-associated variants and underscores the finding that interpretation of skin immunolabeling and molecular diagnostics can be challenging. We provide recommendations on management of this complex syndrome.

Loss of α6 and β4 integrin expression caused by germ line mutations in ITGA6 and ITGB4 usually leads to junctional epidermolysis bullosa (JEB) with pyloric atresia (PA) (JEB-PA; Online Mendelian Inheritance in Man #226730). However, recent studies have suggested that integrin-associated JEB may occur without PA but with other symptoms of the epithelial tissues. Here, we present a case of a Chinese woman with JEB without PA but with profound urinary symptoms. Mutation analysis revealed that the patient carried compound heterozygous mutations in the ITGB4 gene: a frameshift mutation c.600dupC (p.Phe201Leufs*15) and a novel missense mutation c.599C>G (p.Pro200Arg). Our report not only raises the question of whether the designation JEB-PA is appropriate, but also expands our current knowledge of the ITGB4 mutation spectrum.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a heterogeneous group of rare genetic skin disorders characterized by fragility of the skin and mucous membranes. The prevalence of all types of EB is estimated at approximately 11 per million, based on recent data from the American National Epidermolysis Bullosa Registry.
METHODS: A national registry of EB has not yet been established in Slovenia. Because all cases of EB are diagnosed and treated at our department, we have collected data on all known cases of EB in Slovenia.
RESULTS: Based on our data, the prevalence of all EB types in Slovenia is about 20 per million. As of December 2020, our data consist of 29 EB simplex, three junctional EB, 10 dominant dystrophic EB, and four recessive dystrophic EB patients.
CONCLUSIONS: The prevalence of all EB types in Slovenia is higher compared to the estimated prevalence in the United States. The multidisciplinary care of EB patients in Slovenia has been developed based on patients\' needs, including a wide group of various specialists, and it has been adapted to the resources and treatment options available. This article also reviews the up-to-date classification and diagnostic protocol for EB, and international recommendations for interdisciplinary patient care.

Epidermolysis bullosa (EB) is a hereditary mechanobullous disease of animals and humans, characterized by an extreme fragility of the skin and mucous membranes. The main feature of EB in humans and animals is the formation of blisters and erosions in response to minor mechanical trauma. Epidermolysis bullosa is caused by mutations in the genes that code for structural proteins of the cytoskeleton of the basal keratinocytes or of the basement membrane zone. Based on the ultrastructural levels of tissue separation, EB is divided into the following three broad categories: epidermolysis bullosa simplex, junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. Human types of EB are divided into several subtypes based on their ultrastructural changes and the mode of inheritance; subtypes are not fully established in animals. In humans, it is estimated that EB affects one in 17,000 live births; the frequency of EB in different animals species is not known. In all animal species, except in buffalo with epidermolysis bullosa simplex, multifocal ulcers are observed on the gums, hard and soft palates, mucosa of the lips, cheek mucosa and dorsum of the tongue. Dystrophic or absent nails, a frequent sign seen in human patients with EB, corresponds to the deformities and sloughing of the hooves in ungulates and to dystrophy or atrophy of the claws in dogs and cats. This review covers aspects of the molecular biology, diagnosis, classification, clinical signs and pathology of EB reported in animals.

BACKGROUND: Squamous cell carcinoma (SCC) is the most severe complication and most common cause of death in patients with recessive dystrophic epidermolysis bullosa. The risk of developing SCC among patients with junctional epidermolysis bullosa (JEB) is unclear from the literature; however, in our center we noticed an unexpected number of SCCs among adult patients with JEB.
OBJECTIVE: To review all documented patients with JEB in whom an SCC developed, both from our epidermolysis bullosa (EB) center and those reported in the literature.
METHODS: A search in our EB registry documenting all JEB patients visiting our EB referral center from 1990 through 2010 revealed 7 JEB patients who developed 1 or more SCCs. A systematic literature search revealed 8 relevant articles documenting a total of 7 patients who developed an SCC.
RESULTS: In our EB registry we found 7 patients with JEB who developed an SCC; these were all adults classified with non-Herlitz type JEB. The frequency of developing an SCC among adult JEB patients (n = 28) in our center was therefore 25%. In the literature, we found 7 case reports of JEB complicated by SCC (also classified as JEB, non-Herlitz type), bringing the total number of documented cases to 14. The first SCC in JEB patients developed at an average age of 50 years (median, 52 years; range, 28-70 years). In 9 of 14 cases, multiple primary SCCs occurred, with a total of 45 SCCs. The SCCs are most often located on the lower extremities, in areas of chronic blistering, long-standing erosions, or atrophic scarring. Three patients (21%) developed metastases and died on average 8.9 years after diagnosis of the initial SCC.
CONCLUSIONS: This study was retrospective and the statistical analyses were based on a small number of patients.
CONCLUSIONS: From their third decade, adult patients with JEB have an increased risk (1:4) of developing SCC on their lower extremities. The SCCs have a high recurrence rate and follow an aggressive course that results in death in 1 of 5 patients. We recommend annual checks of all JEB patients for SCC starting at 25 years of age.

OBJECTIVE: The junctional form of epidermolysis bullosa (EB) is a recessively inherited mechanobullous disease in which minimal trauma results in blister formation at the dermal-epidermal junction. A rare form associated with pyloric atresia (JEB-PA) is a severe clinical subtype leading to rapid demise after birth, thus justifying prenatal diagnosis. The case characterized by abnormal ultrasound findings at 35 weeks of gestation (gastric dilatation associated with polyhydramnios) of a patient with no family history is reported.
METHODS: Postabortion skin biopsies were analyzed by immunofluorescence that revealed marked reduction of integrin alpha6beta4 in accordance with the diagnosis of JEB-PA.
RESULTS: Amniotic fluid contained excess total protein (4 MoM), abnormally high AFP (20.4 MoM) related to skin lesions and abnormally elevated digestive enzyme suggestive of fetal vomiting of bile. The electrophoretic pattern of cholinesterases was unusual (additional slow band). Maternal serum AFP was 3.14 MoM and free beta-hCG 13.1 MoM. Because of these concomitant findings, JEB-PA was suspected.
CONCLUSIONS: The case under study was atypical because of late clinical manifestations of the disease: polyhydramnios, gastric enlargement. As maternal serum AFP at 15 weeks may be normal, it was suggested that discovery of polyhydramnios during the second or the third trimester should prompt biochemical analysis of amniotic fluid, such as AFP and GGTP assay in all cases.

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The term epidermolysis bullosa (EB) encompasses a heterogeneous group of genodermatoses, characterised by fragility and blistering of the skin, often associated with extracutaneous manifestations. The clinical picture comprises severe subtypes with lethal outcome in the first years of life as well as milder subtypes with localised blistering or minimal symptoms confined exclusively to nail or teeth abnormalities. We present the case of a male infant, who was born with a few bullae and rapidly developed extensive blistering of the skin. The disease was complicated by painful erosions of the oral mucosa, refused ingestion, and recurrent infections. The child died at the age of 4 months because of cardiac failure due to severe sepsis. Antigen mapping of a skin biopsy showed a split within the lamina lucida of the epidermal basement membrane zone and junctional epidermolysis bullosa (JEB) was diagnosed within the first 3 weeks of life. Markedly reduced staining for laminin 5 indicated the Herlitz type of JEB (OMIM 226700), which could be confirmed by mutation analysis in the LAMB3 gene, showing homozygous nonsense mutations.
CONCLUSIONS: early antigen mapping using antibodies against the proteins affected in epidermolysis bullosa, is a useful tool providing early mutation analysis and valuable prognostic information needed for adequate therapeutic strategies. The recently published literature on current diagnostic procedures and the revised classification system for inherited epidermolysis bullosa aim towards a better understanding of the disease.