The ectoderm that covers the developing embryo is initially a single-layered epithelium, the surface ectoderm (Fig. 25.1A). This layer proliferates and forms a layer of surface epithelium, the periderm (Fig. 25.1B), which covers the developing epidermis until the cornified cell layer is formed. The embryonic epidermis begins to stratify at approximately 8 weeks’ estimated gestational age (EGA), and is followed by cornification (composed of ‘dead’ keratinocytes held together by proteins and lipids). Until about 19 weeks’ gestation, the fetal skin is highly permeable and early in gestation, amniotic fluid volume is mostly determined by fetal surface area. At 19 weeks, keratinization occurs and the skin becomes impermeable. When differentiation is complete, the periderm detaches from the underlying epidermis, and its remnants form the vernix caseosa (greasy coat that protects the skin in utero from the amniotic fluid). The epidermis is morphologically similar to adult skin by mid third trimester (Fig. 25.1C). However, it does not acquire full barrier function until a few weeks after birth.

Skin conditions that are a result of genetic abnormalities in the epidermis and/or its appendages often follow a distribution pattern (Fig. 25.2, Table 25.1) representing the migration pathways of epidermal cells during embryonic development. The pattern follows Blaschko’s lines (described by the German dermatologist, Alfred Blaschko) and represent a manifestation of cutaneous mosaicism. Cutaneous mosaicism occurs when two or more genetically different populations of cells exist side by side within the skin. They have typical patterns: V-shaped on the upper spine, S-shaped on the abdomen, linear on the arms and legs, spiral on the scalp and vertical in the mid-face. Many congenital and acquired skin conditions can follow Blaschko’s lines (see Table 25.1). An example of this is an epidermal naevus, which occurs as a result of a defect in ectoderm, leading to an overgrowth of the epidermal keratinocytes. It presents at birth or in early infancy, often with a localized, linear, warty, hyperpigmented plaque. Hypomelanosis of Ito (naevoid hypopigmentation) on the other hand, presents with hypopigmented streaks that follow Blaschko’s lines. Both conditions must be differentiated from incontinentia pigmenti, which is a neurocutaneous disorder syndrome due to a defect in the NEMO gene. This condition presents typically in the newborn with blisters that also follow Blaschko’s lines. The blisters then resolve and reveal hyperkeratotic, warty plaques, followed by increasing pigmentation at 2–6 months of age. The hyperpigmented brown streaks later fade into atrophic hypopigmented streaks in later childhood. These conditions may have associated extracutaneous manifestations, e.g. epidermal naevus, incontinentia pigmenti and hypomelanosis of Ito are associated with central nervous system, heart, eye, skeletal system and dentition defects, McCune–Albright syndrome is associated with bone and hormonal abnormalities, and focal dermal hypoplasia is associated with eye, musculoskeletal, renal, gastro­intestinal, cardiac and neurological abnormalities. The mode of inheritance needs to be ascertained in order to provide appropriate genetic counselling for family members.

Genetic abnormalities that result in a more global abnormal epidermal differentiation and barrier formation can give rise to the presentation of a ‘collodion baby’ (baby born encased in a taut, shiny, transparent membrane that is formed by aberrant stratum corneum) (Fig. 25.5). The membrane is shed over the first 2–3 weeks of life. In the majority of cases, the shedding will then reveal a phenotype of ichthyosis, a cornification disorder due to a genetic abnormality resulting in persistent dry and scaly skin.

Strawberry birthmarks (infantile haemangioma) (Fig. 25.6) are thought to be a result of proliferation of endothelial cells and mutations in genes that encode for vascular endothelial growth factor (VEGF) and other pathways that affect the vascular development. They usually present shortly after birth (unlike vascular malformations – malformed dilated blood vessels in the skin, which are usually present at birth). Infantile haemangiomas are common in the head and neck area, and usually proliferate in the first 6–9 months. This is followed by spontaneous involution over several years and therefore active non-intervention is advised. However, treatment should be considered for lesions which are large with potential for disfigurement, ulcerating, threaten vital function, e.g. vision, hearing, breathing or feeding, or cause high-output cardiac failure. Until recently, steroids (topical, intralesional and oral) were the mainstay of treatment. However, the serendipitous discovery of a non-selective oral beta blocker as an effective treatment has revolutionized its management. Oral propranolol has become the treatment of choice for complicated lesions. The exact mechanism for its action is not completely understood, but is postulated to inhibit angiogenesis and recruitment of endothelial progenitor cells as well as inducing apoptosis. More recently, topical beta blockade in the form of eye drops (usually used for glaucoma) applied directly to the lesions has been shown to be effective.

A number of genes are involved in the formation and migration of neural crest cells. Genetic mutations causing defects in the neural crest can lead to the development of neurocutaneous syndromes (i.e. disorders that affect the skin and are associated with CNS and other abnormalities). Examples of neurocutaneous syndromes include tuberous sclerosis, neurofibromatosis and Sturge–Weber syndrome (Table 25.2).