Table 1. Epidermal disorders with associated genes and processes affected.
| Disease | Mutated Genes | Process Affecteda | Phenotype |
|---|---|---|---|
| Pachyonychia Congenita | KRT 6a, 16, 17 | IF | Hk, nail dystrophy |
| Epidermolytic Hyperkeratosis | KRT1, KRT10 | IF | Blistering, Hk |
| Epidermolysis Bullosa Simplex | KRT5, KRT14 | IF | Trauma-induced blistering with minimal scarring |
| Icthyosis with Confetti | KRT10 | IF | Blistering, Hk, pale confetti-like spots |
| Epidermolysis Bullosa Simplex-Ogna | PLEC1 | BMZ Adhesion, Hemidesmosomes | Trauma-induced blistering |
| Junctional Epidermolysis Bullosa | LAMA3, LAMB3, LAMC2, COL17A1, ITGB4, ITGA6 | BMZ Adhesion | Generalized blistering and erosions |
| Dystrophic Epidermolysis Bullosa | COL7A1 | BMZ Adhesion | Generalized blistering of skin and erosions with scarring |
| Lethal Congenital Epidermolysis Bullosa | JUP | Desmosomes | Generalized blistering and erosions, alopecia, onycholysis |
| Palmoplantar Keratoderma | JUP, PG, DSP, DSG1, KRT9, KRT16, KRT1 | CA, Desmosomes, IF | Hk affecting palms and soles, curly hair, arrythmia |
| Neonatal Ichthyosis Sclerosing Cholangitis Syndrome | CLDN1 | TJ | Sclerosing cholangitis, ichthyosis, hypotrichosis, dental abnormalities |
| Generalized Peeling Skin Disease | CDSN | Desmosomes | Pruritus, patchy peeling of entire skin |
| Netherton's Syndrome | SPINK5 | Desmosomes | Hk, hair shaft defects |
| Exfoliative Ichthyosis | CSTA | CA | Scaly skin and peeling of non-erythematous skin on the palms and soles |
| Vohwinkle Syndrome | LOR, GJB2 | CE, Gap Junction | Honeycomb Hk on palms and soles |
| Erythrokeratodermia variabilis | GJB3, GJB4 | Gap Junction | Hk, transient patches of erythema |
| Ichthyosis vulgaris | FLG | CE | Dry, scaly, itchy skin covering entire body (Hk) |
| Lamellar Ichthyosis | TGM1, ABCA12, ALOX12B, ALOXE3, ICHTHYIN, CYP4F22 | CE, FA & Chol. metabolism | Hk with scales and erythema covering entire body |
| Recessive X-linked Ichthyosis (RXLI) | STS | FA and Chol. metabolism | Large, brown scales covering limbs and trunk |
| Harlequin's Ichthyosis | ABCA12 | FA and Chol. metabolism | Hk, severe form of congenital ichthyosis with grave prognosis |
| Darier Disease | ATP2A2 | Ca2+ signaling | Hk affecting the seborrheic areas |
| Hailey-Hailey Disease | ATP2C1 | Ca2+ signaling | Hk affecting the flexural areas |
| Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate | TP63 | Transcription | Fusion of eyelids, epidermal erosion, dystrophic nails, wiry hair, cleft lip/palate |
| Multiple Self-healing Squamous Epithelioma | TGFBR1 | Signal transduction | SCC-like invasive tumors |
| Noonan Syndrome | PTPN11, KRAS | MAPK signaling | Heart, skeletal, hematologic and cognitive defects, distinctive facial dysmorphisms, Hk, lymphedema |
| Cowden's Syndrome | PTEN | PI3K/Akt signaling | Hamartomas of skin and mucosal surfaces |
| Cardio-facio-cutaneous (CFC) syndrome | KRAS, BRAF, MEK1/2 | MAPK signaling | Heart and cognitive defects, distinctive facial dysmorphisms, Hk, sparse hair |
| Costello Syndrome | HRAS | MAPK signaling | Similar to CFC syndrome in addition to loose skin of hands and feet |
| Nevus Sebaceous | HRAS | MAPK signaling | Hairless plaque on scalp with distinct orange color and pebble-like texture |
| Pilomatricoma | CTNNB1 | CA, Wnt signaling | Solitary hard, subcutaneous nodule |
a
Abbreviations: IF, intermediate filaments; Hk, hyperkeratosis; BMZ, basement membrane zone; CA, cell adhesion; TJ, tight junction; CE, cornified envelope; FA, fatty acid; Chol., cholesterol.