Table 1: Genotype-phenotype correlation in keratinocytic epidermal nevi
|
Gene |
Mutations |
Clinical features of nevi |
Histologic features of nevi |
Other associated features |
|
KRT1 or KRT10 |
Heterozygous dominant negative (only in nevus) |
Verrucous, keratotic plaques; may be thick and spiny or have shedding of scale; palmoplantar involvement (esp. with KRT1 mutations) |
EHK |
None |
|
KRT16 (V1 domain) |
Heterozygous dominant negative (only in nevus) |
Verrucous, keratotic plaques limited to palm(s) and sole(s) |
EHK |
(? Nail dystrophy, follicular keratoses, and oral leukokeratosis as in pachyonychia congenita) |
|
FGFR3 or PIK3CA |
Heterozygous activating (only in nevus) |
Soft, velvety-to-papillomatous plaques; more pronononced in body folds; sparing of palms and soles |
No EHK |
FGFR3: craniofacial dysmorphism, other skeletal abnormalities, developmental dealy, risk of bladder carcinoma
|
|
PTEN |
Homozygous loss-of-function: germline + 2nd hit in nevus |
Thick, papillomatous plaques (Cowden nevus) |
No EHK |
Segmental Overgrowth, Lipomas, Ateriovenous Malformations (SOLAMEN); macrocephaly; later onset trichilemmomas, acral keratoses, and oral papillomas; risk of breast, thyroid, and endometrial carcinoma |
|
Unknown Proteus syndrome gene |
Unknown |
Thin, smooth plaques |
No EHK |
Progressive, asymmetric, disproportionate overgrowth; cerebriform connective-tissue nevi, slow-flow vascular malformations, dysregulated adipose tissue |
EHK, epidermolytic hyperkeratosis
FGFR, fibroblast growth factor receptor
KRT, keratin
PIK, phosphatidylinositol 3-kinase
PTEN, phosphatase and tensin homolog
A Blaskolinear configuration, variable hyperigmentation, and histopathologic findings of acanthosis, papillomatosis, and hyperkeratosis
may be observed in all variants.