Clinical genetics of familial keloids

Background: Keloids are proliferative fibrous growths that result from an e xcessive tissue response to skin trauma. Most keloids occur sporadically, b ut some cases are familial. However, the genetics of keloid formation have only rarely been documented, and the mode of inheritance is not known. Objective: To elucidate the clinical genetic characteristics of keloid woun d-healing disorder. Observations: We studied the clinical and genetic characteristics of 14 ped igrees with familial keloids. The ethnicity of these families is mostly Afr ican American (n = 10), but also white (n = 1), Japanese (n = 2), and Afric an 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 a re female. The age of onset varies from early childhood to late adulthood. There is variable expression of keloids within the same families: some affe cted members have only minor earlobe keloids, whereas others have very seve re keloids affecting large areas of the body. In the described pedigrees, 7 individuals are obligate unaffected carriers, revealing nonpenetrance in a bout 6.8% of keloid gene carriers. Syndromes associated with keloids, namel y Rubinstein-Taybi and Geominne syndrome, were not found in these families. Additionally, linkage to the gene loci of these syndromes and X-chromosoma l linkage were excluded. Conclusions: The pattern of inheritance observed in these families is consi stent with an autosomal dominant mode with incomplete clinical penetrance a nd variable expression. This is the most comprehensive collection of keloid families described to date, and it allows for the first time the elucidati on of the clinical genetic characteristics of the familial form of this wou nd-healing disorder.