Epidermolysis Bullosa Simplex 3, Localized or Generalized Intermediate, with Bp230 Deficiency (EBS3)Q82.8

Epidermolysis bullosa simplex, autosomal recessive with Bp230 deficiency/EBS3is a mild, autosomal recessive inherited genodermatosis characterized by trauma-induced blistering that occurs mainly on the mechanically exposed areas of the feet and ankle parts. Ultrastructural analysis of skin biopsies shows abnormal formation of hemidesmosomes with poorly formed internal plaques (Liu et al. 2012).

Detected mutations in the DST gene (Liu L et al. 2021). By whole-exome sequencing and direct sequencing, Ganani et al. (2021) identified biallelic mutations in the DST gene in affected members of three Israeli families with localized EBS.

Groves et al (2010) reported on a 38-year-old man from Kuwait born of consanguineous parents who suffered from epidermolysis bullosa simplex. He had a lifelong history of trauma-related spontaneous blisters and erosions that particularly affected his ankles and feet, although the face, trunk, and more proximal limbs were also affected. The blisters and erosions healed without scarring or milia formation. The patient also had nail dystrophy and moderate dental caries. The hair was normal. No blistering of the mucosa. Electron microscopic analysis of a skin biopsy showed discrete abnormalities of hemidesmosomes, with poorly formed inner plaques leading to a translucent zone between keratin filaments and outer hemidesmosome plaques that had no gross abnormalities. Immunofluorescence staining revealed the absence of BPAG1 at the dermal-epidermal interface and in keratinocytes. In addition, decreased immunoreactivity for beta-4 integrin, PLEC1 (601282), and COL17A1 (113811) was detected.

The patient's 4 siblings, parents, and 2 children had no skin abnormalities. In addition to skin blistering, the patient suffered from CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy/ OMIM: 125310), a hereditary cerebrovascular disease that begins in middle adulthood with recurrent subcortical ischemic strokes and cognitive deficits and progresses to dementia. CADASIL is due to a heterozygous mutation in the NOTCH3 gene (600276) .

Liu et al (2012) reported a 34-year-old Iranian woman with lifelong blistering that worsened in summer and after trauma, such as friction points of clothing. Blistering occurred mainly on the ankles, feet, dorsal sides of the hands, and elbows. Hair, nails, mucous membranes, or genitals were not affected. Subtle atrophic scarring was present on the shins, ankles, elbows, dorsum of the hands, and lower back.

Electron microscopy of the skin biopsy showed abnormal hemidesmosomes with poorly formed inner plaques and a translucent zone between keratin filaments and outer hemidesmosome plaques. Immunostaining for BPAG1-e showed complete absence of the protein in the patient's skin sample. Her father and two of her three children also had mild blistering. None of them had neurologic abnormalities.

Ganani et al (2021) described 5 patients from 3 families with localized EBS and a mutation in the DST gene. Family was a consanguineous Israeli family of Iraqi origin in which two sisters, aged 48 and 49 years, had bladder disease since childhood. Their father and paternal grandmother also reported recurrent blisters. The feet and hands were most affected, as were other sites exposed to mechanical pressure. Other features included postinflammatory hypopigmentation, delayed wound healing, calluses, and asymptomatic plantar keratoderma, as well as nail dystrophies in isolated cases. Biopsy revealed subepidermal blisters with positive collage IV staining at the base of the blister.

1. Ganani D et al. (2021) Epidermolysis bullosa simplex due to bi-allelic DST mutations: case series and review of the literature. Pediat. Derm 38: 436-441.
2. Groves RW et al. (2010) A homozygous nonsense mutation within the dystonin gene coding for the coiled-coil domain of the epithelial isoform of BPAG1 underlies a new subtype of autosomal recessive epidermolysis bullosa simplex. J Invest Derm 130: 1551-1557.
3. Liu L et al. (2021) Autosomal recessive epidermolysis bullosa simplex due to loss of BPAG1-e expression. (Letter) J Invest Derm 132: 742-744.