Epidermolysis bullosa simplex with pyloric atresia and mutation in PLEC Q82.8

Epidermolysis bullosa simplex with basal clefting and pyloric atresia (EBS5C) is an early lethal autosomal recessive genodermatosis with mutations in the PLEC gene, characterized by severe blistering over large areas already present at birth and by congenital pyloric atresia.

Molecular basis: Mutation in the PLEC gene (601282.0006). Suspected impaired interactions between plectin and the alpha-6/beta-4 integrin within binding structures expressed during gastrointestinal development. There may be molecular overlap with epidermolysis bullosa junctionalis with pyloresatresia (JEB-PA: OMIM: 226730) in which mutations are present in the ITGA6 and ITGB4 genes encoding these integrins.

Cowton et al (1982) reported a female infant born with epidermolysis bullosa, focal aplasia cutis, and pyloric atresia. The mother had elevated alpha-fetoprotein in early pregnancy.

Morrell et al (2000) reported a male infant with consanguineous parents who had numerous skin erosions and intraepidermal (basal cleft) blisters at birth. The skin was largely absent from the face, trunk, and limbs. Other abnormalities included malformed auricles fused to the scalp, hypoplastic nostrils, and joint contractures.

Abdominal radiographs and clinical signs indicated pyloric atresia, which was surgically repaired. He died of respiratory failure at 5 weeks of age.

Charlesworth et al (2003) reported on three sisters born to consanguineous Turkish parents. Clinical features included congenital absence of nasal skin, skin fragility with blistering, and dysmorphic features such as deep-set eyes, hypoplastic ears, hypoplastic nose, and joint contractures. The pregnancies were complicated by polyhydramnios.

Nakamura et al (2005) reported 3 patients from 2 unrelated families with EBSPA. In the first family, 2 brothers were born with multiple blisters and ulcers on all body sites. Pyloric atresia was detected by ultrasound during the pregnancies. Both infants died at 16 and 4 months of age, respectively. Electron microscopy revealed cleavage at the base of basal keratinocytes and hypoplastic hemidesmosomes in all patients. Immunohistology: decreased or absent expression of PLEC1.

Pfendner and Uitto (2005) reported 4 consanguineous families in which at least one member had EBSPA. All patients had extensive bubble formation at birth, pyloric atresia, extensive aplasia cutis. The infants died shortly after birth. Molecular analysis confirmed homozygous mutations in the PLEC1 gene.

Charlesworth et al (2003) identified a homozygous mutation in the PLEC1 gene (601282.0006) in three Turkish sisters with fatal EBSPA.

Nakamura et al (2005) identified a heterozygous mutation in the PLEC1 gene in 2 unrelated patients with fatal EBSPA (see 601282,0007; 601282,0008).

Epidermolysis bullosa simplex generalized severe (Dowling-Meara)(type 1A) (OMIM:131760).

Epiermolysis bullosa junctionalis with pyloric atresia (JEB-PA; 226730), a phenotypically similar disorder caused by a mutation in the ITGB4(147557) or ITGA6 gene (147556).

Death usually occurs in infancy.

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