Peeling Skin Syndrome 5

A number sign (#) is used with this entry because of evidence that peeling skin syndrome-5 (PSS5) is caused by homozygous mutation in the SERPINB8 (601697) on chromosome 18q22.

Description

Peeling skin syndrome-5 (PSS5) is characterized by superficial peeling of the dorsal and palmar skin of the hands and feet; the skin of the forearms and legs may also be involved. Some patients exhibit diffuse yellowish hyperkeratotic palmoplantar plaques (Pigors et al., 2016).

For a general phenotypic description and a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300).

Clinical Features

Pigors et al. (2016) studied 3 unrelated families with exfoliative ichthyosis. The first was a consanguineous family from Tunisia, in which a brother and sister exhibited painless superficial peeling of small areas of the palmar and dorsal skin of the hands and feet, with underlying erythema. The symptoms were present from age 3 months and were aggravated by heat, humidity, and friction. In the second family, from the United Arab Emirates, an affected female patient showed a similar phenotype to that of the Tunisian sibs but also had peeling skin on her forearms. In the third family, an Ashkenazi Jewish family from Israel, 3 affected sibs had onset of symptoms between 4 and 6 months of age and presented with more severe peeling than in the first 2 families. Examination showed superficial white scaling over the lower extremities with no significant erythema, as well as diffuse yellowish hyperkeratotic plaques over the palms and soles. Family history revealed that the maternal grandfather and his sister had psoriasis (see 177900). Skin biopsy in 1 of the Ashkenazi Jewish sibs showed acanthosis, hyperkeratosis, and disadhesion of keratinocytes in the basal and suprabasal layers of the epidermis, with evidence of intercellular space widening.

Mapping

By high-resolution homozygosity mapping in affected members of a Tunisian family with peeling skin syndrome, Pigors et al. (2016) identified a shared region of homozygosity on chromosome 18 between SNPs rs1944983 and rs2194631.

Molecular Genetics

By whole-exome sequencing in a shared region of homozygosity in affected members of a consanguineous Tunisian family with mild exfoliative ichthyosis involving peeling skin of the hands and feet, Pigors et al. (2016) identified a homozygous 1-bp deletion in the SERPINB8 gene (601697.0001). The mutation segregated with disease in the family. Analysis of the SERPINB8 gene in 10 additional patients with a similar phenotype detected a homozygous missense mutation (601697.0002) in a patient from the United Arab Emirates. Exome sequencing in an Ashkenazi Jewish family from Israel with a similar phenotype revealed homozygosity for a SERPINB8 nonsense mutation (R284X; 601697.0003) that segregated with disease.