Porokeratosis 8, Disseminated Superficial Actinic Type

A number sign (#) is used with this entry because of evidence that disseminated superficial actinic porokeratosis-8 (POROK8) is caused by heterozygous mutation in the SLC17A9 gene (612107) on chromosome 20q13.

Description

Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shape, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), the existence of several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, suggest that the distinctions among these variants may be artificial.

Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012).

For a discussion of genetic heterogeneity of porokeratosis, see 175800.

Clinical Features

Cui et al. (2014) studied 2 unrelated Chinese families segregating autosomal dominant disseminated superficial actinic porokeratosis. The proband in the first family was a 39-year-old woman who developed tiny papules on her face at age 20 years. The characteristic annular keratin lesions spread centrifugally, and primarily involved the cheeks, forehead, and area around the eyes. She had 2 affected brothers; their mother and a maternal uncle were also affected. The proband in the second family was a 19-year-old man with numerous tiny papules on the face, as well as an annular lesion with atrophic fovea and raised horny borders in the eyelid. His affected 46-year-old father displayed numerous bean-sized brown keratotic plaques, distributed on the face, chest, and forearms. None of the affected individuals had carcinoma.

Inheritance

Male-to-male transmission of DSAP in a family reported by Cui et al. (2014) supported autosomal dominant inheritance.

Molecular Genetics

Cui et al. (2014) performed exome sequencing in 2 affected and 1 unaffected individual from a 3-generation Chinese family with DSAP, in which mutation in the MVK (251170), SART3 (611684), and SSH1 (606778) genes had been excluded. They identified a heterozygous missense mutation in the SLC17A9 gene (R311Q; 612107.0001) that segregated with disease and was not found in controls. Sequencing of SLC17A9 in 6 more affected families and 19 sporadic patients, also known to be negative for mutation in the MVK, SART3, and SSH1 genes, revealed another heterozygous missense mutation (R9C; 612107.0002) in an affected father and son.