Clinical genetics of familial keloids

Keloids are proliferative fibrous growths that result from an excessive tissue response to skin trauma. Most keloids occur sporadically, but some cases are familial. However, the genetics of keloid formation have only rarely been documented, and the mode of inheritance is not known.

To elucidate the clinical genetic characteristics of keloid wound-healing disorder.

We studied the clinical and genetic characteristics of 14 pedigrees with familial keloids. The ethnicity of these families is mostly African American (n = 10), but also white (n = 1), Japanese (n = 2), and African Caribbean (n = 1). The pedigrees account for 341 family members, of whom 96 displayed keloids. Of the affected family members, 36 are male and 60 are female. The age of onset varies from early childhood to late adulthood. There is variable expression of keloids within the same families: some affected members have only minor earlobe keloids, whereas others have very severe keloids affecting large areas of the body. In the described pedigrees, 7 individuals are obligate unaffected carriers, revealing nonpenetrance in about 6.8% of keloid gene carriers. Syndromes associated with keloids, namely Rubinstein-Taybi and Goeminne syndrome, were not found in these families. Additionally, linkage to the gene loci of these syndromes and X-chromosomal linkage were excluded.

The pattern of inheritance observed in these families is consistent with an autosomal dominant mode with incomplete clinical penetrance and variable expression. This is the most comprehensive collection of keloid families described to date, and it allows for the first time the elucidation of the clinical genetic characteristics of the familial form of this wound-healing disorder.