As the epidermis develops in the first four months, some neural crest cells migrate superficially to become melanocytes, interposed within the epidermal strata. The theoretical paths of dorsal melanocytes, migrating laterally from the midline but stretched by the flexed fetus, is one potential basis for lines of normal cell development called Blaschko's lines. The lines appear V-shaped on the back, S-shaped on the chest, hourglass-shaped on the face, and swirled on the scalp. Certain autosomal and X-linked inherited skin conditions are affecting keratinocytes and melanocytes, such as epidermal naevus, hypomelanosis of Ito, incontinent pigmenti, and also acquired conditions such as lichen striatus, linear morphea tend to follow a Blaschkoid distribution as a visible manifestation of genetic mosaicism. In women, some X-linked disorders follow a Blaschkoid distribution as a result of normal X-inactivation (lyonization), resulting in functional cutaneous mosaicism; one example is X-linked hypohidrotic ectodermal dysplasia. Interestingly, the implicated gene in X-linked ichthyosis, which encodes steroid sulfatase, is known to "escape" X-inactivation and therefore does not follow Blaschko's lines. The genetic pathways for melanocyte migration and development is a complex process facilitated by several genes such as MITF,c-KIT, Snail/Slug, protooncogenes such as BRAF and NRAS, tumor suppressor genes such as CDKN2A and endothelins like EDNRB. All of these genes carry implications in the pathogenesis of Malignant Melanoma. Out of these, mutations in BRAF and NRAS are present in nearly 65% and 20% of melanomas, respectively. [4]Certain pigmentary disorders such as Piebaldism, where leukoderma and a central forelock of white depigmented hair are vital features, involve a mutation in the c-KIT gene. [5][6][7][8]

On the soles of the palms and feet, the surface changes resulting from the formation of epidermal ridges are the basis for fingerprints and are determined genetically. Certain genetic diseases, such as Down syndrome, often affect ridge pattern formation, resulting in distinctive phenotypes like the presence of a transverse palmar crease(simian crease), which can aid in diagnosis.

Several subtypes of ectodermal dysplasia appear to result from mutations in p63 of the p53 family of transcription factors, which is first expressed at week 8.5 of embryogenesis and appears to play a key role in epidermal stratification. It is thought to exert its effects via maintenance of the epidermal stem cell population and basal layer. Homozygous knockout mice for the p63 gene are born with a single-cell-thick layer of skin rather than a recognizable epidermis, and consequently, expire secondary to dehydration. The phenotype was similar enough to subtypes of congenital ectodermal dysplasia that researchers sought a connection. Indeed, there is a subgroup of ectodermal dysplasia, which links to p63 mutations. These include Hay-Wells syndrome, and ectodermal dysplasia-ectodactyly clefting syndrome, inherited in an autosomal dominant fashion and are principally characterized by ectodermal dysplasia, orofacial clefting, and limb malformations.[9]

The embryonic growth and patterning of epidermal stem cells, hair follicles, and sebaceous glands are under partial regulation by the molecular signals of the Hedgehog pathways, including the sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh) pathways. These pathways are most active during embryogenesis, but they also play a role in postnatal hair follicle growth and epidermal stem cell replenishment. As basal cell carcinoma appears to arise from immature pluripotential cells associated with the hair follicle, it is not surprising that most sporadic basal cell carcinomas contain mutations in the Hedgehog pathways. Inactivating mutations in PATCHED (PTCH), a tumor suppressor in the Shh pathway, are most common. Another 10-20% is caused by activating mutations of smoothened (Smo), the protooncogene, which PTCH normally represses. Additionally, nevoid basal cell carcinoma syndrome (NBBCS, Gorlin syndrome), which is characterized by the development of extracutaneous tumors, skeletal and dermatologic anomalies, and dozens to hundreds of BCCs by early adulthood, is nearly always caused by PTCH mutations. Orally active small-molecule inhibitors of the Shh pathway, such as Vismodegib and Sonidegib, have demonstrated clinical efficacy in the treatment of locally advanced or metastatic basal cell carcinoma and NBCCS.[10][11]