Keratoacanthoma familial D23.L

Rare autosomal-dominantly inherited tumor disease first described in individuals of Scottish origin, but also observed in other populations, characterized by newly developing keratoacanthomas over years and decades. The initial manifestation of the disease is in late childhood, in contrast to the non-hereditary form.

Mutations in the TGFBR1 gene (transforming grwoth factor beta receptor1), which is located on gene locus 9q22.

Mostly occurring in early adulthood (average age is 52.6 years).

Chronically light-exposed areas of the body. Face, trunk, extremities.

A generalized, familial disease that first manifests in early adulthood with multiple, solitary but also aggregated, skin-coloured or reddish-brownish horny papules (with somewhat longer existence, formation of a central horny plug - typical picture of the classic keratoacanthoma), which can heal with scarring and mutilation. The aggressiveness and expressiveness of the disease increases significantly with age.

Mutiple autosomal dominant keratoactnhomas due to mutations in NLRP1. Eruptive, multiple, ulcerative, hyperkeratotic, painless, reddish-brown nodules and lumps on plantar and palmar skin.

Ferguson Smith (1934) first described this condition in a single case, a 23-year-old miner who first developed spots on his legs at the age of 16. The lesions healed spontaneously but were replaced by others on adjacent sites and later on the face and ears. After healing, an atrophic scar remained. The lesions resembled squamous cell carcinoma clinically and histologically. Ferguson-Smith later reported that the patient died 14 years later from "purulent meningitis." Affected areas included the face, ears, arms, and legs, as well as the skin of the anus, scrotum, and anterior abdominal wall. All tumors were well-differentiated squamous epitheliomas. The anal tumor infiltrated the sphincter and muscle coating of the anal canal.

Sommerville and Milne (1950) reported 2 cases in each of 2 consecutive generations. Degos et al (1964) described the disease in 1 wife and 2 daughters.

Ferguson-Smith et al (1971), the geneticist and son of the dermatologist who first described this disease, studied 62 cases in western Scotland. The lesions occurred more frequently on exposed areas of the skin. Two girls had their first lesion in their thirteenth year; the oldest occurrence was in a male aged 56 years and in a female aged 55 years. The mean age of onset was 25.5 years in females and 26.9 years in males.

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