Palmoplantar Keratoderma and Erythrokeratoderma

Gene: PERP

Green List (high evidence)

Four families reported with heterozygous variants and Olmsted syndrome-2 (OLMS2), which is characterised by mutilating hyperkeratotic skin lesions, primarily on the palms and soles, but also extending onto dorsal surfaces of the hands and feet and distal extremities. The lesions are progressive, becoming thicker with verrucous fissures on the palms and soles over time. In addition, affected individuals exhibit perioral hyperkeratosis, and may have lesions around other orifices as well, such as the nostrils, perineum, and anus. Most patients also have hyperkeratotic nails and light-colored woolly hair. Two families reported with bi-allelic variants and Erythrokeratodermia variabilis et progressiva-7 (EKVP7), which is characterised by palmoplantar keratoderma that extends to the dorsal surface of the hands and feet (transgrediens), as well as erythematous annular skin lesions. Pruritis, woolly hair, and dystrophic nails may also be present.

Created: 3 Mar 2021, 2:44 a.m. | Last Modified: 3 Mar 2021, 2:44 a.m.

Panel Version: 0.94

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Olmsted syndrome 2, MIM# 619208; Erythrokeratodermia variabilis et progressiva 7, MIM# 619209

Publications

• 31898316
• 30321533
• 31361044

Red List (low evidence)

One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP.

A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature

Created: 4 Jun 2020, 2:42 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Erythrokeratoderma, no OMIM # yet

Publications

• PMID: 31898316