An Update of Childhood Genetic Disorders


Cynthia A. Prows, Divisions of Human Genetics and Patient Services, Building E. 5.259, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039. E-mail:


Purpose: Thousands of single gene, mitochondrial, and chromosomal disorders have been described in children. The purpose of this article is twofold. The first is to increase nurses’ awareness of new developments in genetic disorders that are commonly seen in practice and taught in schools of nursing. The second is to illustrate important genetic concepts of relevance to nurses who care for infants, children, or adolescents.

Organizing Construct: This article is organized into four sections: one that describes new developments in a well-known disorder, a second that discusses the process and potential outcomes of diagnosing a very rare disorder, and the third and fourth sections that describe select conditions caused by single gene mutations.

Methods: Clinical expertise was paired with literature review to present evidence-based current information. Implications for nursing practice are highlighted throughout the article. Citations of publicly available evidence-based online resources are used so nurses can continue to use these in their practices.

Findings: Diagnosis and treatment strategies for children with genetic disorders are rapidly changing. While it is impossible to stay current in all disorders, resources are available to help nurses provide evidence-based care to children with genetic disorders.

Clinical Relevance: Nurses have an important role in the early identification of children with genetic disorders and in facilitating their access to appropriate services and resources. Nurses can also help families understand why genetic testing may be necessary and assure families are informed throughout the process.

Genetic disorder is the umbrella term used for diseases or syndromes caused by variants affecting nuclear or mitochondrial genes, combinations of variant genes and environmental factors, or changes in the number or structure of one or more chromosomes or chromosomal regions. The Online Mendelian Inheritance in Man (OMIM; contains descriptions of over 12,000 disorders associated with known or suspected Mendelian or mitochondrial etiology, or chromosome deletions or duplications. To promote nurses’ efforts to meet genetics-genomics competencies (Consensus Panel on Genetic/Genomic Nursing Competencies, 2009), this article features a small number of genetic disorders to (a) raise awareness of new developments in genetic disorders that are commonly seen in practice and taught in schools of nursing; and (b) to illustrate important genetic concepts of relevance to nurses who care for infants, children, or adolescents. The section on Down syndrome (DS) illustrates why it is important for nurses to stay current in commonly recognized genetic disorders. The neonate with hypotonia demonstrates the process and potential outcomes of early evaluation by a genetics clinician (physician or advanced practice nurse with specialty training in genetics). The autosomal dominant section reviews important concepts that impact a nurse's ability to recognize indications for referral in children with and family members at risk for a genetic disorder. The autosomal recessive (AR) section reviews the role of ethnicity in genetic risks and uses cystic fibrosis as an example of advances in early recognition and targeted therapies.

New Developments in a Well-Known Disorder: Down Syndrome

DS, the most frequent genetic cause of cognitive impairment, occurs in approximately 1 in 700 live births in the United States (Parker et al., 2010). Current estimates suggest there are over 400,000 people in the United States with DS (National Down Syndrome Society, 2012) and over 6 million people with DS worldwide. Life with DS in the 21st century is dramatically different than it was when the condition was first described by Dr. John Langdon Down in 1866. Improved health care, the support of families and advocacy groups, and the expansion of educational and vocational opportunities have led to improvements in quality and longevity in the lives of individuals with DS. Life expectancy has increased from 12 years in 1929 to nearly 60 years at present (Bittles & Glasson, 2004). In addition, a growing number of individuals with DS are graduating from high school, going to college, living independently, and finding employment. However, the inclusion of individuals with DS into educational, vocational, and social opportunities depends in large part on the attitudes of others, and findings from two recent studies suggest that many people continue to hold negative attitudes toward individuals with DS (Pace, Shin, & Rasmussen, 2010, 2011). Nurses can play an important role in educating the public about the potential of people with DS and participate in policy deliberations regarding the inclusion of adults with DS.

Although clinical presentation is variable, all individuals with DS have some level of cognitive impairment, usually mild (IQ of 50–70) or moderate (IQ of 35–50). In addition, many have distinctive facial features such as an upward slant to the eyes, a depressed nasal bridge, a short neck, and abnormally shaped ears. Common health concerns for individuals with DS include hearing loss (75%), vision problems (60%), obstructive sleep apnea (50%–79%), otitis media (50%–70%), eye disease (60%), and congenital heart defects (50%). A thorough discussion of these, as well as other health concerns associated with DS, can be found in the most recently revised evidence-based guidelines published by the American Academy of Pediatrics (Bull, 2011). In addition to including age-specific recommendations for health monitoring, the guidelines recommend annual assessment of (a) personal support available to family, (b) participation in a family-centered medical home, (c) financial and medical support programs for which the child and family may be eligible, (d) injury and abuse prevention with special consideration of developmental skills, and (e) nutrition and activity to maintain fitness.

Until recently, most individuals in the medical and research community believed it was impossible to reverse or reduce cognitive impairment. However, recent advances in genomics and brain research are providing new directions for possible drug therapy designed to improve the cognitive and adaptive abilities of individuals with DS. The studies are funded in large part by foundations and institutes specifically interested in DS (e.g., Down Syndrome Research and Treatment Foundation, Research Down Syndrome, Linda Crnic Institute for Down Syndrome, Global Down Syndrome Foundation) and have helped researchers identify a number of unique biological mechanisms associated with cognitive impairment in DS. One such mechanism is an imbalance between excitatory and inhibitory neurotransmission in the hippocampus, an area of the brain that is critical for learning and memory. Researchers have used mouse models of DS (e.g., Ts65 Dn mice) to demonstrate that balance in the hippocampus can be restored by blocking receptors responsible for inhibition (Fernandez et al., 2007). Another group of researchers have shown that memantine, a drug approved for the treatment of Alzheimer's dementia, can reverse learning and memory deficits in Ts65 Dn mice (Costa, 2011). Clinical trials investigating the safety, tolerability, and efficacy of potential drug therapy informed by animal studies are underway.

Recently, there have been a number of national efforts designed to address two of the major barriers facing researchers interested in DS: (a) lack of adequate funding and (b) lack of a national DS registry. In 2011, two pieces of legislation were introduced in the U.S. Congress by the Co-Chair of the Congressional Down Syndrome Caucus, Representative Cathy McMorris Rodgers. The first bill, H.R. 2696, the Trisomy 21 Research Resource Act of 2011, authorizes current efforts already underway by national patient advocacy organizations, together with the National Institute of Child Health and Human Development to establish three research databases that will provide the research community with access to information that has been otherwise hard to obtain. The second bill, H.R. 2695, the Trisomy 21 Centers of Excellence Act of 2011, recognizes six centers of excellence dedicated to conducting and coordinating translational research in DS and requests that $6 million be allocated annually to the National Institutes of Health (NIH) to fund these centers of excellence. In September of 2011, the NIH joined with organizations interested in DS to form a consortium designed to foster the exchange of information on biomedical and biobehavioral research on DS. A central focus of the consortium is implementation of the NIH Research Plan on Down Syndrome developed by the NIH Down Syndrome Working Group in October 2007 (Eunice Kennedy Shriver National Institute of Child Health and Human Development, 2007).

There is growing excitement among families of children with DS, advocacy groups, and DS researchers about research designed to understand and reduce impaired cognition in individuals with DS and research aimed at improving the quality of life for individuals with DS. Yet, there is growing concern about research on DNA sequencing of maternal plasma to detect DS such as that described by Palomaki et al (2011). At the time of this writing, noninvasive diagnostic testing for DS was being commercially offered in many major cities in the United States. One of the main concerns voiced about this new type of testing is that it may lead to a reduction in the number of individuals with DS being born, which could ultimately lead to a reduction in services for individuals with DS and funding for DS research (Greely, 2011; Leach, 2011; Van Riper & Choi, 2011). A recent report by the Council for Responsible Genetics (Haymon, 2011) thoroughly discusses some of the complex ethical and social implications of noninvasive diagnostic testing for DS (e.g., freedom of choice in reproductive decision making, justice and access to care, stigmatization, and disability rights). It is critical that families are given the information needed to make informed decisions about both genetic testing and involvement in clinical trials. Informed nurses and other healthcare providers can advocate for and facilitate dialogue between pregnant women, expectant families, healthcare providers, families of individuals with DS, disability advocates, and DS researchers about genetic testing options for DS as well as available trials for improving cognition and quality of life.

Hypotonia in the Newborn: Rare Disorders

Nurses have an important role in recognizing hypotonia in the newborn and making or facilitating a genetics referral when caring for a newborn commonly described as “floppy.” On physical examination, a hypotonic newborn has limited voluntary movement, reduced strength, and joints that have increased range of movement and diminished resistance when manipulated. Hypotonia is one of the most common reasons for considering a genetic disorder in a newborn. However, many neonates with hypotonia do not have a disorder as widely recognizable as DS. A genetics clinician must conduct a comprehensive evaluation to narrow down the diagnostic possibilities from many hundred genetic and nongenetic conditions that may present with hypotonia. Even when a medication or other treatment that specifically targets a condition is not available, an accurate diagnosis can inform prognosis and guide management to maximize developmental and health potential as well as prevent secondary complications. For example, hypotonia due to Zellweger syndrome (Steinberg, Raymond, Braverman, & Moser, 2003, update 2011) is very different from hypotonia associated with Prader-Willi syndrome (Cassidy & Schwartz, 1998, update 2009) or congenital myasthenia gravis (Abicht & Lochmuller, 2003, update 2012). The first of these conditions is lethal; the second is compatible with long-term survival but is associated with lifelong challenges and disability; the last can be serious and even life threatening at birth, but if due to transplacental transmission of antibodies, it can resolve in the first few months of life.

Depending on the setting or country of practice, nurses at the bedside may facilitate access to a genetics consult. All nurses can prepare families for the evaluation and assure that their subsequent questions and service needs are met. Nurses can describe that during a genetics consultation a patient with hypotonia may be examined by a clinical geneticist or, in a few settings, a genetics advanced practice nurse. These clinicians or a genetic counselor will obtain prenatal and perinatal histories to identify exposures, infections, or other events that can lead to fetal damage. Existing family history data in the medical record will be reviewed. Because pedigrees are seldom documented, a three- to four-generation family history with specific questions aimed at features of potential inherited disorders that present with neonatal hypotonia will be obtained. A genetic clinician's physical examination always includes a dysmorphology assessment to identify patterns of phenotypic variations that can be found in specific disorders. Nurses who want to learn more about dysmorphology are referred to the 2009 American Journal of Medical Genetics Part A special issue, “Elements of Morphology: Standard Terminology,” which provides descriptions, definitions, and pictures of common and variant phenotypic features. Findings from the clinician's comprehensive genetics evaluation inform the testing approach.

Tests to evaluate a neonate with hypotonia may include (a) measuring metabolic analytes if a condition such as Zellweger syndrome (Steinberg et al., 2003, update 2011) is suspected; (b) interrogating chromosomes by high-resolution karyotyping if a recognizable chromosome disorder such as DS is suspected; (c) testing for abnormal methylation patterns when a condition due to imprinting such as Prader Willi syndrome is suspected; (d) analyzing specific genes when a condition such as congenital myasthenia gravis (Abicht & Lochmuller, 2003, update 2012) is suspected. When the genetic history and examination does not uncover a readily recognizable pattern, a chromosomal single nucleotide polymorphism (SNP)-based microarray test may be performed (Conley, Biesecker, Gonsalves, Merkle, Kirk, & Aouizerat, 2013; Miller et al., 2010). Please see Gene Tests or Genetic Home Reference listed in Clinical Resources for more information about specific tests.

An example of a condition that can present with newborn hypotonia and was once thought to be very rare before chromosomal microarrays became available is 1p36 deletion (Battaglia & Shaffer, 2003, update 2008). This deletion was first described in 1981, but the phenotype was not clearly delineated until the late 1990s. With the advent of microarray technology, the incidence of 1p36 deletion has been found to be 1 in 5,000 to 10,000 children (Battaglia et al., 2008). Several case series have been published (Battaglia, et al., 2008; Battaglia & Shaffer, 2003, update 2008; Gajecka, Mackay, & Shaffer, 2007) that provide insight into knowing when to consider 1p36 deletion and what problems to anticipate for the newly diagnosed child. The presenting features are nonspecific but consist of hypotonia and feeding problems in the neonatal period. This is often accompanied by recognizable but minor abnormalities in facial features and less frequently by major malformations like heart defects, cleft lip, or cleft palate. As the children with deletion 1p36 grow older, they are often slower to master developmental skills than other children the same age. This is particularly true for language and communication, but also impacts motor skills and global development. The developmental outcomes are varied, and children are usually more severely impaired than children with DS. The affected children may also have other health problems like slow growth, seizures, and chronic aspiration of oral contents into the trachea. However, this condition has been widely recognized for only a few years, so information on long-term outcomes is limited.

The juxtaposition of rapidly advancing genetics technology and information technology has provided the opportunity for parents of children newly diagnosed with very rare disorders to interact regardless of where they live. Families living with rare diseases have used social networking resources to connect with one another and to share ideas and information. When families of patients of the second author initially looked for information on 1p36 deletion, they were dismayed to find little was available. One family responded to this by raising money to support production of a brochure for families that was nationally distributed and is still in use (personal observation, second author). Another family used social networking to sponsor a site for discussion that has led to a national support group. The 1p36 support group now sponsors an annual family meeting and is working with physicians and scientists to increase not only awareness but scientific and medical understanding of the disorder affecting their families (1p36 Deletion Support and Awareness, 2012). Similar online networking and advocacy groups have been developed for many rare genetic disorders. Social media can bring together families, healthcare providers, and scientists so that management plans and research studies focus on priorities that impact the health and quality of life for their children (Landy et al., 2012). This networking is expected to have an increasing impact on healthcare delivery and research, especially for rare disorders.

Conditions Caused by Single Gene Mutations: Autosomal Dominant Disorders

An autosomal dominant disorder is recognizable in the heterozygous state, which has classically referred to a pair of genes at a specific locus in which one of the genes has a mutation that changes the function of the protein in a deleterious manner. Autosomal dominant disorders may occur due to a de novo mutation (new mutation that spontaneously occurred in a gene carried by an individual germ cell) or can be inherited. Improved technology can now detect chromosome deletions and duplications too small to detect with routine chromosome analysis (categorized as submicroscopic chromosome imbalances). Most of these imbalances occur spontaneously and are thus unique to the individual with the associated disorder. However, when a submicroscopic chromosome imbalance is contained on an autosome (chromosomes 1–22) and the resulting disorder does not prevent reproduction in the affected adult, then it is possible for the de novo submicroscopic chromosome imbalance to be transmitted to subsequent generations in an autosomal dominant pattern. A good example is velo-cardio-facial syndrome, which is due to a submicroscopic deletion in chromosome 22 that is usually de novo but can be transmitted to subsequent generations (McDonald-McGinn, Emanuel, & Zackai, 1999, update 2005). When the submicroscopic imbalance is on an X chromosome and the adult is able to reproduce, then the imbalance can be transmitted in an X-linked pattern. Clinical recognition of these disorders can be confounded by reduced penetrance, variable expressivity, and pleiotropy. Each of these concepts will be explained and clinical examples given in the following section.

Reduced penetrance is a population-based concept. It refers to the proportion of people with a causative gene mutation who have observable or measurable manifestations of the disorder. When 100% of people who inherit the mutation develop one or more features of the disorder, no matter how mild, the mutated gene is considered 100% penetrant.

Achondroplasia (a type of short-limbed dwarfism) is an example of an autosomal dominant disorder caused by a mutation in the FGFR3 gene that is 100% penetrant and recognizable during childhood and usually infancy (Pauli, 1998). Achondroplasia is due to a de novo mutation in 80% of children with the disorder. Although their parents do not have achondroplasia, children with the de novo mutation have a 50% chance of transmitting the mutation to each of their future children.

Van der Woude syndrome (VWS) is a rare autosomal dominant craniofacial disorder with reduced penetrance recognizable in childhood that is caused by particular mutations in the IRF6 gene (Durda, Schutte, & Murray, 2003, update 2011). Most children with VWS inherited it from a parent since de novo mutations are not common. Approximately 80% of people with a mutation will demonstrate one or more features of the condition. The phenotype also demonstrates variable expressivity even between affected family members. The more common features of VWS include lower lip fistulae (pits) or mounds, cleft lip, cleft palate, or any combination of the three main features. VWS is a good example of variable expressivity because individuals within a family may have one or any combination of these congenital craniofacial anomalies, and the degree of severity will also vary. Reduced penetrance or variable expressivity misleads people to think conditions like VWS “skip generations.” When an “unaffected” adult has a parent and a child with VWS, the unaffected adult has the gene mutation; it did not skip the adult. The mutation is either not penetrant in that individual or it is possible that the adult's very mild expression was unrecognized, the latter of which is an example of variable expressivity.

Neurofibromatosis type 1 (NF1) is a relatively common (incidence 1 in 3,000) autosomal dominant disorder that demonstrates pleiotropy and variable expressivity. Pleiotropy refers to findings that have the same cause but are otherwise seemingly disconnected. For example, manifestations of the gene mutation can be found in more than one body system. Mutations in the NF1 gene are virtually 100% penetrant. Some signs of the condition may not be recognizable until after childhood (Friedman, 1998, update 2009). The NF phenotype is pleiotropic because clinical manifestations can involve the skin, eyes, bones, peripheral or central nervous system, cardiovascular system, or any combination of these. Expression of the NF1 mutation transmitted within a family can vary considerably, with some individuals having only specific cutaneous findings such as café au lait spots (that may be thought of as insignificant “birth marks”), while others may have aggressive tumors or malignancies that cause significant morbidity or death. Since obvious signs and symptoms can be delayed until adolescence or adulthood, children with an affected parent need to be carefully monitored. A symptom-free child may have the NF1 mutation transmitted within a family but the features are not yet recognized earlier in life. Delayed or mild manifestations in early childhood do not necessarily predict a milder case of the disorder as he or she ages.

Nurses need to consider concepts such as reduced penetrance, variable expressivity, and pleiotropy demonstrated by many dominant disorders when collecting family history and identifying individuals who may benefit from genetic information or services. For example, although cleft lip is most often an isolated anomaly associated with a 3% to 5% recurrence risk (Bender, 2000), VWS illustrates that a congenital anomaly, like cleft lip, may actually be a manifestation of an underlying disorder with a 50% recurrence risk. Each of the dominant conditions discussed illustrates some rate of de novo mutation. However, to determine if a child's disorder is due to a de novo or inherited mutation in conditions such as VWS and NF1, the parents need to be carefully examined by a professional skilled in dysmorphology and knowledgeable about the spectrum of signs and symptoms for the disorders. These disorders also illustrate the importance of nurses recording seemingly unrelated problems, signs, symptoms, or features when obtaining a three-generation family health history.

Early recognition and diagnosis of a genetic disorder can inform targeted screening, early intervention, prevention of secondary complications, education strategies, and social connections that can improve quality of life. Identification of the variant gene and subsequent understanding of the molecular and cellular consequences of particular mutations can lead to novel treatments. Development of molecular targeted therapies for dominant conditions has been particularly difficult since targeted therapies for autosomal dominant conditions need to prevent the production of the mutated proteins that can interfere with the normal protein produced by the normal allele. This is in contrast to AR disorders that result in deficient or absent protein for which protein replacement therapy may be an option. Targeted therapies in autosomal dominant conditions are being studied which use specially designed probes that cause naturally occurring cellular mechanisms to degrade the messenger RNA of the mutated gene, thus preventing the abnormal protein from being produced. This then allows the wild-type (normal) gene's protein to function. However, there are several significant problems to overcome, such as rapid degradation of probes and getting probes to specific target tissues. Comprehensive reviews of animal and human research using this technology were recently published by Davidson and McCray (2011) and Kole, Krainer, and Altman (2012). The use of genetic testing prior to such therapies can be compared with the use of antibiotic sensitivities to pick the best antibiotic for the “same infection” in different people. Genetic testing prior to targeted therapies is particularly important for disorders in which a single disorder can be caused by a mutation in one of several possible genes.

Autosomal Recessive Disorders

AR disorders result when both alleles of a gene contain a mutation that contributes to the disorder. Children who have one functional allele and one disease-associated allele are called carriers and do not develop signs and symptoms of the disorder. When these children reach reproductive age, if their partner is also a carrier of a mutation in the same gene, they are at 25% risk with each pregnancy of having a child with the disorder.

Mutant alleles responsible for AR diseases are generally rare; these alleles may be transmitted in families for many generations without their awareness. Unlike dominant mutations that interfere with the functional allele's protein, recessive mutations typically result in reduced or nonfunctional protein product, and the remaining wild-type allele's functional protein is adequate for its intended purpose. It has been estimated that every person is a carrier of 8 to 10 recessive mutant alleles. However, analysis of whole exome and whole genome sequencing has revealed that the genome from healthy individuals contains approximately 100 loss-of-function variants, most of which are expected to be in nonessential genes (MacArthur et al., 2012).

The chance that both parents are carriers for the same mutation increases in genetic isolates (a community isolated from the general population due to geography, ethnicity, or other factors) and in consanguinity (both parents share a biologic relative in common). Both raise the prevalence of rare AR disorders. In genetic isolates, since these populations cohabited within themselves for many generations, the frequency of specific AR diseases is high. Typically a distinct mutation shared by all individuals with the rare AR disease reveals a founder effect (Peltonen, 2005). An example of genetic isolates is the Finnish disease heritage, a group in which about 30 AR diseases occur more frequently than in the general population. Each of the 30 diseases has a major founder mutation (Pastinen et al., 2001). Consanguinity is common in some ethnic groups such as Arab communities in the Middle East (El Mouzan, Al Salloum, Al Herbish, Qurachi, & Al Omar, 2008), yet low in many Western countries as it may carry a social stigma, causing patients to avoid sharing this information with their care providers (Mensink & Hand, 2006). Nurses need to establish an open and honest relationship with their patients in order to obtain an accurate family history that may reveal consanguinity.

Until recently, carriers were detected only after an affected child was born. However, carrier screening for relatively common AR diseases such as cystic fibrosis (CF) and sickle cell disease now makes it possible to detect healthy carriers before conceiving an affected pregnancy. Some tests are recommended to all, while others are offered according to ethnic origin (Borry et al., 2011). The test panel may change in response to findings from epidemiologic or genetic studies or new genetic technologies. These tests may examine common mutations in a given population, and accordingly the mutation panel might be updated when new mutations are identified. For this reason, nurses need to be aware that in some cases a person who was previously tested and found to not be a carrier for any of the analyzed mutations might benefit from being retested in the future after new mutations are identified and added to the panel. CF is a good example of a disorder for which the carrier panel was specifically designed to detect mutations commonly found in different racial and ethnic populations. In those cases when targeted mutation screening does not capture the mutations in a given ethnic group, additional steps might be required, such as gene sequencing. It is important that nurses who work in women's health or perinatal settings keep current knowledge about available testing panels and help their patients obtain the information they need to make informed decisions regarding testing. This can be achieved by being involved in related professional organizations, developing collaborations with genetics professionals, or keeping in close contact with a genetics clinic.

Traditionally, the reproductive choices available to two carriers were either to avoid having biologic children or to have prenatal testing after conception. When a fetus was diagnosed with a disorder, the couple had to decide to either terminate the affected pregnancy or prepare for the delivery and care of a child with the disorder (Harper & Sengupta, 2012). When the mutation in each carrier parent is known, preimplantation genetic diagnosis (PGD) is now an additional option. Couples using PGD undergo in vitro fertilization (IVF), let the embryos develop for 3 to 5 days, and then remove one or two cells for genetic testing, allowing selection of the embryos that are not at risk for the AR disorder and for transfer to the uterus (Harper & Sengupta, 2012). The most frequent AR diseases tested in PGD are CF, beta-thalassemia, and sickle cell disease (Demko, Rabinowitz, & Johnson, 2010). PGD has lately been expanded to test over 200 dominant, recessive, and X-linked as well as some chromosomal disorders. PGD can also be used for sex selection when an X-linked disorder is known to run in the family but the causative gene mutation is not known. PGD does have disadvantages, including the risks and stress associated with the IVF procedure (Harper & Sengupta, 2012) and the fact that IVF and PGD are expensive and often not covered by insurance, which leads to unequal access to available options.

While knowing the mutated genes in different diseases enables identification of carriers, it also stimulates advances in the development of new therapies. CF is such an example. Approximately 1,500 different functionally significant mutations have been described in the CF transmembrane conductance regulator (CFTR) gene. The common functional CFTR allele produces a protein that is an adenosine triphosphate–dependent chloride channel. Most of the variant CFTR alleles are private (when a specific mutation is reported in only one family) or rare, and appear with different prevalence according to race and ethnicity. The exception is ΔF508, a three–base pair deletion causing a frameshift mutation at codon 508 that accounts for 70% of the CF-associated mutations worldwide (Becq, Mall, Sheppard, Conese, & Zegarra-Moran, 2011). Developing drugs for 1,500 different mutations in a rare disease is not feasible. Classifying CFTR mutations into five categories according to the mechanism of altered CFTR (protein) function improved the feasibility of developing mutation targeted therapy. For example, ΔF508 produces a protein with abnormal folding that prevents the protein from leaving the endoplasmic reticulum. However, the abnormally folded protein has been shown to have partial function if able to reach the cell membrane. Studies to discover or develop compounds that can rescue the variant CFTR and escort it to the cell membrane are being conducted (Becq et al., 2011). Another category of mutations creates proteins that are successfully transported to the cell membrane but do not function, yet may function when patients with these types of mutations are given a CFTR potentiator medication (Ramsey et al., 2011) that was recently approved by the Food and Drug Administration (Davis, Yasothan, & Kirkpatrick, 2012). However, the medication is not effective in people who carry two copies of the common ΔF508 allele (Flume et al., 2012). Nurses will need to help patients understand why different medications are being prescribed for patients that share the same clinical diagnosis.


The genetic disorders featured in this article demonstrate that recognition, diagnosis, and treatment strategies for children with genetic disorders are rapidly changing. It cannot be expected that nurses remain current in all genetic disorders or genetic tests. It is important, however, to be familiar with expert, peer-reviewed, regularly updated resources that are freely accessible on the Internet and have been described or cited in this article. Nurses have an important role in assessing and identifying patients who may benefit from a genetics evaluation; preparing families for a genetics consultation; coordinating related testing, procedures, and care; and helping families process the information they learned from the consultation process. Informed nurses can assure that patients and families are aware of available support groups and clinical trials that may benefit them. Development of drugs tailored to specific mutations or categories of mutations require nurses to anticipate the need to explain to families why children with the same diagnosis are receiving different treatments.

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