Multifactorial disorders are diseases that are influenced by the interaction of a number of different genes scattered throughout the genome. These genes work in concert with one another, and are often regulated by environmental or behavioral factors. Multifactorial genetic conditions like acne, eczema, alopecia, and psoriasis affect as many as one in four individuals in some communities, virtually guaranteeing that all nurses will encounter patients with an inherited skin disease at some point.
Atopic dermatitis, or eczema, is very common in some communities, affecting nearly 15% of the children in industrialized countries (Hoffjan & Epplen, 2005). Symptoms usually appear in childhood, often disappearing over time, but occasionally persisting, or manifesting in adulthood. At least five genes have been associated with atopic dermatitis, but mutations in the filaggrin (FLG) gene are known to play a significant role in atopic dermatitis, other forms of eczema, ichthyosis vulgaris, and other severe dry skin conditions (Smith & McLean, 2011; Weidinger et al., 2006). The FLG mutation produces an abnormal keratin-filament aggregating protein causes skin corneodesmosomes to break down prematurely, impairing the epidermal barrier. When exposed to irritants like soap and detergents or proteases produced by dust mites or Staphylococcus aureus, allergens may penetrate the already damaged skin barrier, inciting an inflammatory cascade and exacerbating the disease. Atopic dermatitis is a good example of the role that the environment can play in disease exacerbations. It also highlights the variability of disease manifestations, because not all severely affected patients have an FLG mutation, and not all people with an FLG mutation develop eczema.
It is estimated that 2% to 10% of people worldwide have psoriasis, an autoimmune disorder characterized by patches of itchy, scaly skin. Psoriasis symptoms vary widely, and individuals with severe disease report health-related quality-of-life degradation similar to individuals with chronic diseases, such as depression, hypertension, congestive heart failure, or type 2 diabetes (Sampogna et al., 2006). Although the exact cause is unknown, environmental triggers and genetic predisposition have both been found to play major roles in the development of psoriasis. In a recent twin study, approximately two thirds of the risk for psoriasis could be explained by genetics and the remaining one third could be attributed to shared environmental risk factors (Grjibovski, Olsen, Magnus, & Harris, 2007).
Genetic susceptibility to psoriasis appears to be primarily mediated through genes controlling T cell–mediated immune response. In normal skin, a cell matures and is shed in 28 to 30 days, but in psoriasis, skin cells mature in as little as 3 to 4 days and scaly patches of thick skin rapidly build up, forming psoriatic lesions, triggering further immune responses. The most significant psoriasis gene is in the human leukocyte antigen (HLA) gene complex, specifically the HLA-Cw*0602 allele. Individuals with one copy of the HLA-Cw*0602 allele are at increased risk for developing psoriasis when exposed to an environmental trigger (Liu et al., 2008). Other genes, such has interleukin (IL)-12B and IL-23R have also been implicated in the development of psoriasis, and interestingly, although neither is in the HLA family, both are involved in immune modulation. In addition to its influence on autoimmune inflammatory disease, IL-23 is suspected to play an important role in tumorogenesis (Gene Cards, 2011).
Many health professionals can describe X-linked inheritance patterns and identify at least a few X-linked disorders, but may not be aware that the inheritance pattern they are describing is for an X-linked recessive disorder. In an X-linked recessive disorder, women usually do not manifest symptoms because one of their X chromosomes can produce enough normal protein that they remain asymptomatic. If a male inherits the X with the mutation from his mother, he will express symptoms because he does not have a second X producing normal protein. This is an important characteristic of X-linked disorders; 50% of males born to a carrier mother will be affected, and 50% will be unaffected. Females can manifest classic X-linked recessive symptoms if their father is affected and their mother is a carrier, and they inherit two X mutations, but this is uncommon (Smith & McLean, 2011). In an X-linked dominant disorder, only one X mutation is needed for disease to manifest. X dominant disorders are usually severe; affected males are likely to die in utero, and while symptomatic, females are more likely to survive because they have one X that produces at least some functional gene product. Examples of X-linked dominant dermatologic disorders include incontinentia pigmenti (IP), Rett syndrome, and Aicardi syndrome (Pagon, Bird, Dolan, Stephens, & Adam, 2012).
Incontinentia Pigmenti IP is lethal most males, and the disease is rare, affecting approximately 700 females worldwide. The diagnosis is usually made based on clinical features but can be confirmed by skin biopsy or by gene testing, and genetic counseling is challenging because disease expression varies widely (Pettigrew et al., 2000). The earliest IP manifestations are skin lesions that evolve predictably through four stages: blistering from birth to approximately 4 months, a wart-like rash for several months, hyperpigmentation from approximately 6 months into adulthood, and finally linear hypopigmentation. Excess melanin is deposited in the skin, appearing on the trunk and extremities as slate gray, blue, or brown marbled or wavy lines. Other features of IP include alopecia, hypodontia, abnormal tooth shape, and dystrophic nails. Other health problems, including cataracts, retinal detachment, and severe vision loss; cognitive delay and intellectual disability and severe skeletal and structural abnormalities, including hemivertebrae, scoliosis, spina bifida, syndactyly, and acheiria (congenital absence of the hands) may also be seen.
Nurses are directly engaged with patients and their families in every life event, are present in all healthcare settings, and work with all population groups. As a result, patients rely heavily on nurses for advice, support, navigation assistance, and accurate information about health and healthcare. The public expects nurses to understand how genetic conditions are inherited, understand the genetic underpinnings for common conditions, help patients recognize and navigate the ethical issues associated with genetic information, and be familiar with genetic resources so they can help locate genetic information when it is needed. To prepare the nursing workforce for genomic healthcare, the second edition of the Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators was published in 2009 (Consensus Panel on Genetic/Genomic Nursing Competencies, 2009), followed 3 years later by the Essential Genetic and Genomic Competencies for Nurses With Graduate Degrees (Greco, Tinley, & Seibert, 2012). Together, these two documents establish the essential knowledge, education, and practice competencies across the nursing spectrum.
Although nurses are not expected to know every detail of all genetic conditions, they should be familiar with genetic disorders commonly seen in their communities and be prepared to develop individualized care plans for patients and families with genetic concerns. If a genetic referral culminates in a genetic test, nurses should be prepared to discuss the ethical issues that often arise when genetic testing is done. For example, when genetic testing is done to confirm the existence of a suspected genodermatosis, it is not uncommon for another deleterious gene to be identified, which may indicate that the individual is at increased risk for developing another completely unrelated genetic disease, such as Alzheimer's disease. Several ethical issues arise involving disclosure of this incidental genetic information, such as: should the incidental finding be disclosed to the patient or family, and if the findings are disclosed, who does that, and when should it be done?
Ethical issues also emerge when considering gene therapy. There are three primary types of gene therapies: (a) cell therapy involves replacing diseased cells with healthy ones (organ transplant, blood transfusion, and in vitro fertilization); (b) protein therapy involves replacing normal proteins by injecting them into tissues with missing or nonfunctional proteins (less commonly used); and (c) gene therapy (largely experimental) involves the replacement or repair of missing or broken genes (Long et al., 2009). While each has unique ethical issues, overarching concerns include who is offered gene-based therapy, who decides when the therapy is offered, what disorders will be treated, and whether gene therapy will be used to cure disease or create more attractive, intelligent, or athletic human beings (Long et al., 2009).
There are some significant privacy concerns in genomic health care as well. While amazing advances in genomic science are revealing more each day about the underlying mechanisms in health and illness, an individual's personal genetic code also holds information about his or her risk for developing diseases far into the future while simultaneously revealing risks shared by closely related family members. Genomic information could easily be used to discriminate against individuals, their families, and communities. Nurses must therefore be familiar with genetic privacy issues and understand the scope and limitations of the protections offered by the Genetic Information Non-discrimination Act, passed in the spring of 2008. Nurses should be comfortable discussing the concepts of genetic information security, identifiability, consent, and access to stored samples.
Accurate, reliable, up-to-date information on genetic disorders has been made infinitely easier with the advent of the Internet. Over the past two decades, many genetic, scientific, and family advocacy organizations have taken the time to develop detailed, useful, robust, and continually updated Web sites, and concurrent advances in search technologies have made locating these Web sites infinitely faster and easier. Finding information can be an exercise in frustration, however, if the disease name is misspelled or is confused with another, similar disorder. Nurses should therefore ask patients whenever possible to write the disorder down or recommend a reliable site so that learning about an unfamiliar disorder is optimized. Some helpful resources focusing exclusively on skin include the Foundation for Ichthyosis and Related Skin Types (http://www.firstskinfoundation.org/), GeneSkin (http://www.geneskin.org/), and the Human Intermediate Filament Database (http://www.interfil.org).