Skill Checkup: A Student With an Inherited Blistering Condition and Painful Bullae on His Feet

William D. James, MD


April 12, 2021

Pseudosyndactyly (fusion of the fingers) is characteristic of severe recessive dystrophic epidermolysis bullosa (RDEB). In this subtype of DEB, there is a complete absence of collagen VII expression due to biallelic mutations in the COL7A1 gene. Clinically, blisters form from birth and cover the body in a generalized distribution, and pseudosyndactyly of the hands and feet occurs and results in joint contractures. Severe RDEB is associated with extracutaneous manifestations, including blistering and scarring of the gastrointestinal tract and ulcerations of the cornea. Research is underway for CRISPR/Cas9-based correction of COL7A1 mutations to allow for the development of autologous cell therapies for RDEB in the form of skin grafts for the management of wounds in EB patients.

EBS with pyloric atresia is inherited in an autosomal recessive manner. The manifestations of severe EBS with pyloric atresia are the occurrence of blisters in the neonatal period, the presence of pyloric atresia and, frequently, premature death. Mutations in the PLEC (plectin) gene can lead to different subtypes of EBS, one of which is severe EBS with pyloric atresia. JEB with pyloric atresia is associated with mutations in the α6β4 integrin gene. Phenotypic manifestations of this subtype of disease are heterogeneous and include, in addition to pyloric atresia, generalized distribution of blisters, congenital absence of skin, and early lethality in some cases. The pectin protein coded for by the PLEC gene has a role in stabilizing cellular adhesion structures. Pyloric atresia is not reported in DEB cases.      

EBS with muscular dystrophy (EBS-MD) is autosomally inherited and is characterized by the occurrence of blisters since birth and progressive muscle weakness that manifests between infancy and adulthood. Blisters are often hemorrhagic and heal with atrophic scarring and (rarely) milia formation. Extracutaneous manifestations include enamel hypoplasia and dentition decay, respiratory and breathing difficulties secondary to blistering in the respiratory tract mucosa, and neurologic disorders. EBS-MD is a result of mutation in the PLEC gene (one of the plectinopathies) where disruption of the myofilament anchorage to hemidesmosomes eventually results in blistering. It is not reported to occur in DEB.      

Laryngo-onycho-cutaneous (LOC) syndrome is a variant of junctional epidermolysis bullosa (JEB). Autosomal recessive mutations in the gene LAMA3A affect production of the protein alpha-3A laminin. JEB-LOC is characterized by skin erosions, nail abnormalities, and excessive granulation tissue in the conjunctiva and larynx, and by generalized enamel hypoplasia with small, yellow hypoplastic teeth.


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