Using Family History Information to Identify Children with Intellectual and Developmental Disabilities

Janice S. Dorman, MS, PhD and Rebecca Kronk, MSN, CRNP

Abstract

This report describes the importance of nursing in the collection of family history information to identify children with intellectual and developmental disabilities (IDD). For IDD, family history information is a necessary beginning step in determining the underlying etiology of the disorder. It has been estimated that up to 50% of cases of IDD are due to genetic and chromosome abnormalities. Determining the etiology of IDD will facilitate early intervention and support to optimize functioning within the context of the child's specific disabilities and environment. Nurses who are directly involved in this process should be able to perform the needed clinical assessments, determine whether the family would benefit from genetic counseling and/or genetic testing based on their family history, provide appropriate information about services and resources, clarify potential misconceptions about genetic issues, and advocate for confidentiality, privacy, and nondiscrimination. Nurses are prepared to obtain family history information as part of their comprehensive health assessment. However, there are barriers when medical histories are required for extended family members. These include insufficient time to take a comprehensive family history, an underestimation of the value of family history information and limited education in genetics. In addition, nurses often lack the necessary knowledge to make appropriate genetic referrals. This report describes ways to remove these barriers so that nurses can become more directly involved in genetics-related nursing practice.

Keywords: pedigrees , Intellectual disabilities , developmental disabilities , family history , nursing

INTRODUCTION

As of January 1, 2007, the American Association of Mental Retardation (AAMR) became known as the American Association on Intellectual and Developmental Disabilities (AAIDD) (www.aamr.org). The name change is "establishing a new standard in disability terminology and making way for a more socially-acceptable manner of addressing people with intellectual disabilities"¹. The term has also been adopted by the World Health Organization because it stresses health and functioning, which align more with a social model of disability, as opposed to the previously-used personal tragedy model². However, the term mental retardation has been retained for diagnostic purposes within the medical community.

AAMR defines mental retardation as "a disability characterized by significant limitations in both intellectual functioning and in adaptive behavior as expressed in conceptual, social and practical adaptive skills. This disability originates before age 18 years"¹. Adaptive behaviors are assessed using standardized tests that examine factors such as communication, and sensory and motor skills. Cognitive abilities are measured by age-standardized tests that generate Intelligent Quotient (IQ) scores, which determine whether the child has mild, moderate, severe or profound mental retardation³. Mental retardation is, therefore, a heterogeneous group of disorders affecting approximately 3% of the adult population⁴.

Since IQ testing is not appropriate for infants and very young children, those under the age of five years are evaluated in terms of attaining developmental milestones³. However, not all children with developmental delays will become cognitively impaired when they are older. Conditions such as cerebral palsy and some neuromuscular disorders may result in delays in early learning, but with IQ scores in the normal range when the child is deemed eligible for testing. When all developmental disabilities are considered together, it is thought that up to 10% of children have some form of impairment⁴.

This report describes the importance of nursing in the collection of family history information to identify children with intellectual and developmental disabilities (IDD). For IDD, family history information is a necessary beginning step in determining the underlying etiology of the disorder. In 1995, the American College of Medical Genetics sponsored a Consensus Conference to develop recommendations for evaluating children with IDD (Table 1)⁵. The first recommendation emphasized the need for a focused approach in determining the clinical and laboratory evaluations required for diagnostic and treatment purposes. The second recommendation described the importance of a three-generation pedigree as part of the initial clinical assessment.

A pedigree is a graphical representation of the family's medical history and is one of the fundamentals of clinical genetics⁶. It provides essential medical data about the patient and information about biological relationships using standardized nomenclature and symbols. Although pedigrees are typically constructed by clinical geneticists and genetic counselors, nurses are becoming increasingly involved in the development of pedigrees. This is due, in part, to the establishment of Core Competencies in 2001 by the National Coalition for Health Professional Education in Genetics (NCHPEG) for all health care professionals (www.nchpeg.org). Genetic competencies for nurses have also been developed by organizations such as the International Society of Nurses in Genetics⁷ and the American Association of Colleges of Nursing⁸. These and other published competencies were recently reviewed by a panel of national experts to achieve consensus regarding "Essential Nursing Competencies and Curricular Guidelines for Genetics and Genomics" for all nurses in the United States⁹. Competencies represent the minimum knowledge, skills and attitudes necessary for nurses to provide patient care that incorporates genetics and is sensitive to related ethical, legal and social concerns. One of the major skills identified by all core competencies is the collection of genetic family history information and the development of a multi-generation pedigree.

It has been estimated that up to 50% of cases of IDD are due to genetic and chromosome abnormalities^{4, 10}. A pedigree is required before genetic counseling or genetic testing is even considered. Determining the etiology of IDD will facilitate early intervention and support to optimize functioning within the context of the child's specific disabilities and environment. Nurses who are directly involved in this process should be able to perform the needed clinical assessments, determine whether the family will benefit from genetic counseling and/or genetic testing based on their family history, provide appropriate information about services and resources, clarify potential misconceptions about genetic issues, and advocate for confidentiality, privacy, and nondiscrimination.

Nurses are prepared to obtain family history information as part of their comprehensive health assessment. However, there are barriers when medical histories are required for extended family members. These include insufficient time to take a comprehensive family history, an underestimation of the value of family history information and limited education in genetics. In addition, nurses often lack the necessary knowledge to make appropriate genetic referrals. This report describes ways to remove these barriers so that nurses can become more directly involved in genetics-related nursing practice.

IMPORTANCE OF FAMILY HISTORY INFORMATION

On Thanksgiving Day 2004, Dr. Richard Carmona launched the United States' Surgeon General's Family History Initiative by declaring the day as "National Family History Day" (http://hhs.gov/familyhistory/). The purpose of his initiative was to encourage all Americans to learn more about their family health history. He noted that most individuals believe that knowing about their family history is important. However, fewer than half actually have a written record of the diseases that affect their relatives. As a result, he endorsed a new web-based tool, which can be accessed from www.cdc.gov/genomics/public/famhix/links.htm titled "My Family Health Portrait" to help people determine their familial patterns of diseases. This family history tool was also approved by the National Human Genome Research Institute, the Centers for Disease Control, the Agency on Healthcare Research and Quality, and the Health Resources and Service Administration. The American Medical Association, the National Society of Genetic Counselors and other professional groups have developed similar web-based tools. A list of these family history resources is provided in Table 2.

"My Family Health Portrait" and most other family history tools focus on common diseases, including diabetes, heart disease, stroke and cancer (colorectal, breast, ovarian). These disorders were selected for a variety of reasons¹¹. First, the conditions represent a substantial public health burden and have a clear case definition. Thus, it is likely that individuals will be aware of relatives who have been diagnosed with these conditions. In addition, a positive family history has been established as an independent risk factor for these disorders. There are also effective strategies that can be employed for primary and secondary disease prevention. Moreover, personalized health care recommendations can be made for individuals at different levels of risk. Although "My Family Health Portrait" focused on a few common chronic diseases, it can also be used to identify individuals with genetic abnormalities.

COLLECTING FAMILY HISTORY INFORMATION FOR IDD

A search of the Online Mendelian Inheritance in Man (OMIM) database in April 2007 using the term "mental retardation" generated a list of more than 1300 genes. In addition to genetic factors, a wide variety of environmental factors have been identified as playing a role in IDD^{3, 10}. These include exposure during pregnancy to toxic substances (e.g., alcohol, drugs including anticonvulsants), infectious agents (e.g., cytomegalovirus, toxoplasmosis, syphilis, rubella) and prolonged maternal fever. Social factors, such as poverty, limited maternal education and malnutrition are also likely to play a role. In addition, complications during delivery, prematurity, postnatal infections, exposure to lead and head trauma can lead to IDD.

The cause of IDD can be established in approximately 60% to 75% of severe cases¹². Corresponding frequencies for those with mild IDD are significantly lower (approximately 38% to 55%). With advances in molecular genetics and genetic technology, the number of diagnosed IDD cases due to inherited causes will likely increase over time. However, establishing the correct diagnosis can be extremely complex and requires a multidisciplinary approach, including examinations by nurses, clinical geneticists, developmental pediatricians and neurologists. A series of clinical, laboratory and genetic tests will also be needed in the diagnostic process. Interpretation of these results requires a team approach and takes considerable time, in part, because it requires the collection of extended family history information to develop a three-generation pedigree.

Three-generation pedigrees reflect the medical histories of parents, siblings, grandparents, aunts/uncles and first cousins on the maternal and paternal sides of the family. Half-siblings, adopted individuals and occurrences of consanguinity should also be considered. Family history information for IDD can be collected during a face-to-face interview with the affected child's parents or primary caregivers. Constructing pedigrees requires tools such as "My Family Health Portrait" (see resources listed in Table 2) and a checklist of medical conditions that are related to IDD.

The family history tool includes the name, age, ethnicity and living status of the affected child and each of the biological relatives listed above. It also includes information about their affection status. These data can be ascertained using the checklist. Because of the difficulties in diagnosing IDD, it is recommended that the checklist be comprehensive and include the following conditions: mental retardation, learning problems, developmental delays, congenital malformations, birth defects, seizures, speech problems, autism, cerebral palsy, psychiatric disorders and substance abuse^6,13. Infertility, pregnancy losses and infant deaths should be included in the checklist since some genetic causes of mental retardation are not compatible with life. It is also important to explore the age of menopause in the maternal and paternal relatives because genetic conditions associated with mental retardation can cause premature ovarian failure in women¹³. If any family member has a condition listed on the checklist, this information is then recorded directly on the family history tool next to the family member's demographic information. Age at diagnosis should also be included if known. Two relatives with the same genetic defect may express different levels of cognitive and adaptive function, and different behaviors and physical features. Therefore, the family history of IDD may appear to be quite heterogeneous even if the same mutation is the cause of IDD in all affected relatives.

Ideally, the family history tool is completed during a face-to-face interview with the affected child's parents or caregivers, which would typically take at least 30 minutes. In a primary care practice, it is seldom possible to spend that amount of time to discuss family history. However, nurses can help the family begin to complete the form on their own by writing the names of affected child, and each of his/her relatives for whom medical information needs to be collected, in the appropriate space on the family history tool. Nurses can also instruct families about proper use of the checklist. An advantage of this approach is that parents/caregivers can take the checklist and family history tool home and spend as much time as they need to complete it in a private environment. This also facilitates contacts with other relatives who may be able to provide additional information or confirm a suspected diagnosis. Disadvantages of using self-report tools instead of interviews include poor recall, fear of discrimination and ambiguous or misleading wording.

Once completed, the family history tool should be mailed back to the nurse or returned at the time of the affected child's next clinic visit. Alternatively, the form could be mailed to the parents/caregivers prior to the child's appointment so that the information could be collected in advance. However, this does not provide an opportunity for training in the use of the family history tool and the checklist. Irrespective of how the family history information for IDD is collected, the nurse should verify the information by interview, preferably in person. This is particularly important for affected children who are in foster care or those whose biological relatives are unavailable. In such situations, it is important to distinguish an "unknown" family history from a "negative" family history. Ultimately, self-report family history information should be verified by medical records and/or clinical and laboratory evaluations. Examinations of other family members may also be useful⁵.

The nurse also needs to ask the parents/caregivers whether components of the family history tool were confusing or whether there was something they thought was missing from checklist. Once the family history tool is completed, the nurse can construct a pedigree. Organizing family history information as a pedigree is important because it permits an evaluation of possible modes of inheritance. It also allows other health professionals working with the family to see what information has already been collected at a glance.

CONSTRUCTING A PEDIGREE FOR IDD

Pedigrees are easily constructed using one of the web-based family history tools described in Table 2. Beginning with the affected child, also known as the proband or index case, each family member is represented by a square (male) or circle (female) connected by relationship lines. Parents are connected by a horizontal line between a square and a circle. A vertical line of descent (from the parent's relationship line) connects the affected child to his/her biological parents. The affected child and his/her siblings are organized on their horizontal relationship line, from oldest to youngest, left to right. The proband's symbol is shaded, indicating that he/she is affected, and an arrow is placed at the bottom left of his/her symbol for notation purposes. Additional lines can be drawn to connect grandparents, aunts, uncles and cousins. Depending on the size of the family, separate pedigrees can be constructed for the maternal and paternal sides of the family. A complete list of the standard pedigree symbols and formal nomenclature can be found in the reference by Bennett et al., 1995⁶.

Symbols of all relatives identified as having a condition listed on the family history tool should also be shaded, as was done for the affected child. Alternatively, different colors or patterns can be used to distinguish between the conditions or groups of conditions (e.g., disorders identifiable at birth versus those diagnosed during adolescence). The pedigree should also include a legend with the date and name of the nurse who completed it, as well as the codes/patterns used to indicate the presence or absence of IDD or related conditions.

INTERPRETING A PEDIGREE FOR IDD

Pedigrees are initially examined to identify common patterns of inheritance, the characteristics of which are described in Table 3⁶. Since IDD can be caused by environmental factors, some pedigrees may have no recognizable pattern of inheritance. One example is Fetal Alcohol Syndrome, which is one of the most preventable causes of IDD. Children with this disorder have IQ scores somewhat below normal¹⁴. However, even those who are in the normal range have difficulties in terms of attention, verbal learning and executive function, and their social abilities frequently do not progress beyond the level of a six-year-old child.

IDD caused by a single gene defect may become apparent by examining a three-generation pedigree. This requires knowledge of patterns of inheritance (Table 3). As a general review, each individual has 23 pairs of chromosomes, one of which was inherited from the mother (maternal); the other of which was inherited from the father (paternal). One pair represents the sex chromosomes (X and Y); the remaining 22 pairs are known as autosomes (i.e., not sex chromosomes). Females have two X chromosomes (i.e., 46, XX); males have one X and one Y chromosome (i.e., 46, XY).

If a disorder affects only a few relatives of either gender, but occurs in multiple successive generations, it is possible that it follows an autosomal dominant pattern of inheritance (Table 3). An autosomal dominant condition is caused by the presence of one disease gene; its counterpart on the other chromosome is generally normal. Therefore, an affected individual has a 50% chance of transmitting the defective gene to each of his/her children. Children who receive the disease-causing gene will be affected. Those who receive the normal gene will be unaffected and will have no chance of transmitting the disorder to their offspring. An example of IDD with an autosomal dominant pattern of inheritance is tuberous sclerosis, which is due to mutations in either of the two tuberous sclerosis complex (TSC) genes¹⁴. Causative mutations in TSC1, which is located on chromosome 9, or TSC2, which is located on chromosome 16, reflect deletions or changes in the DNA sequence in these chromosomal regions.

Autosomal recessive disorders tend to occur in multiple individuals, of either gender, in just one generation because they require two copies of the defected gene for disease expression (Table 3). Parents of a child with an autosomal recessive disorder are generally unaffected themselves. They each have one copy of the disease-causing gene and one normal gene; they are called "carriers." With each additional pregnancy, there is a 25% chance of having another affected child who has inherited both parents' defective genes. There is also a 25% chance that their child will inherit two normal genes, and a 50% chance that the child will be a carrier. Phenylketonuria (PKU) is an example of mental retardation with an autosomal recessive form of inheritance¹⁴. More than 400 mutations in the phenylalanine hydroxylase gene (PAH), which is on chromosome 12, have been reported to cause PKU.

Single gene defects that cause IDD may also be sex-linked because they are due to mutations on the X chromosome (Table 3). The X chromosome has more mutations that lead to IDD than any other chromosome¹⁰. At least 60 genes on the X chromosome have been associated with mental retardation. One hypothesis is that the X chromosome contains more genes that influence cognitive function than other chromosomes¹⁵. The X chromosome contains about 3% of all genes that have been identified to date. However, it carries 16% of the genes known to be associated with IDD. This may explain the observed excess of IDD in males¹⁶. Therefore, all pedigrees should be carefully examined to determine whether IDD appears to be inherited as an X-linked disorder. X-linked dominant disorders may appear in males and females in a given family, although some are lethal in males. If males have X-linked dominant IDD, the expression of the phenotype may be more severe than it is in females. X-linked recessive disorders are typically expressed only in males. Females are generally unaffected. However, as carriers, they can pass the disease gene to half of their sons, who will be affected, and half of their daughters, who will be carriers. The most common X-linked cause of IDD is Fragile X syndrome.

Fragile X Syndrome

Forty percent of X-linked mental retardation has been attributed to Fragile X syndrome⁵. The prevalence of Fragile X is higher in males (1 in 4,000) than in females (1 in 6,000)³. Fragile X syndrome is due to mutations in the Fragile X Mental Retardation Syndrome - 1 gene (FMR1)¹³. Specifically, a DNA sequence consisting of three nucleotides (CGG) is repeated many more times in the defective gene than it is in the normal FMR1 gene. The normal FMR1 gene contains approximately 7-44 repeats; the causative mutation contains more than 200 repeats. The premutation or carrier state has 55-200 repeats. If a maternal premutation is transmitted, it will always expand in the next generation. For example, if an unaffected mother has a permutation, there is a high probability that her children will inherit the full FMR1 mutation with more than 200 repeats. This does not occur when unaffected males transmit the permutation¹³.

The typical clinical features of Fragile X include long jaw or high forehead, large and/or protuberant ears, and hyperextendible joints; testicular enlargement may only occur in 50% of males⁴. Typical behavior traits include initial shyness and lack of eye contact, followed by friendliness and verbosity. Social and behavioral difficulties associated with Fragile X syndrome include problems with attention, impulsivity, anxiety, social avoidance and arousal³. IQs greater than or equal to 70 occur in 15% of males and 70% of females¹⁷. Declines in both cognitive ability and adaptive behaviors occur with age due to a slower acquisition rate of these skills compared to same-aged peers.

Molecular genetic testing for Fragile X is 99% sensitive and 100% specific. It is considered the diagnostic standard for the disorder¹⁸. Moreover, it is relatively inexpensive and has important implications for the patient and his/her family. According to the College of Medical Genetics (2005), testing should be considered for: 1) all males and females with unexplained mental retardation, developmental delay, and/or autism; 2) individuals seeking reproductive counseling with a positive family history of these disorders; 3) fetuses of known carrier females; 4) individuals whose cytogenetic testing results are inconsistent with the physical expression of their disease; 5) women with reproductive/fertility problems; and 6) individuals with late onset tremor or cerebellar ataxia of unknown origin.

Siblings of Fragile X cases are at increased risk to be asymptomatic carriers and, therefore, may also wish to be tested¹⁹. These individuals can be identified from the patient's family history. The decision regarding if and when siblings should be tested requires serious thought, and has many implications. Before genetic testing is performed, families need to understand that if the unaffected child is diagnosed with Fragile X syndrome, other asymptomatic relatives may also have inherited the mutation. Nurses have a long tradition of being sensitive to emotional and psychological issues related to health. They are ideally suited to provide the type of information and support that families require as they consider predictive genetic testing. Nurses can help parents of children with Fragile X understand the purpose, risks and benefits of genetic testing, and consider potential feelings about disclosing test results, such as psychological distress, stigmatization and discrimination.

Other common heritable causes of IDD are Down syndrome and subtelomeric rearrangements, each of which is described below.

Down Syndrome

Down syndrome (trisomy 21) occurs in about one in 800 live births without predilection for race or socioeconomic status²⁰. It is one of the most frequent genetic causes of mild to moderate mental retardation in males and females²¹. About 95% of Down syndrome children have three rather than two copies of chromosome 21²². Thus, Down syndrome is also known as Trisomy 21. It is often recognized because of its characteristic phenotype, which includes a short head (brachycephaly), flat facial features, with a small nose, hypotonia, upslanted palperbral fissures, epicanthal folds, small abnormally shaped ears and Brushfiled spots²³. Clinical and behavioral characteristics of Down syndrome also include a wide range of impairments¹³. Females are typically less severely affected than males.

Down syndrome is most often due to the abnormal segregation of chromosome 21 during the formation of gametes, which is more likely to occur with increasing maternal age¹³. Therefore, Down syndrome does not follow one of the recognizable patterns of inheritance. However, affected children are easily diagnosed using routine chromosome analysis. Prenatal testing for Down syndrome is recommended for pregnant women who are over the age of 35 years¹³. Nurses can be extremely helpful in preparing these women for genetic counseling and prenatal genetic testing, and possible choices about pregnancy outcomes if the fetus is diagnosed with the disorder.

Since chromosome abnormalities are the single most common cause of IDD, the American College of Medical Genetics recommends that all children suspected to have IDD, even in the absence of positive family history, have high-resolution chromosome analysis⁵. High-resolution chromosome analysis will clearly detect abnormalities in chromosome number, such as Down syndrome. However, it will also detect much smaller defects, including subtelomeric rearrangements.

Subtelomeric Rearrangements

High-resolution chromosome analysis sometimes detects alterations near the ends of chromosomes (subtelomeric regions) and appear to be responsible for approximately 5% of unexplained IDD cases²⁴. The best use of subtelomeric analysis is in individuals with moderate to severe mental retardation associated with physical anomalies²⁵. Good indicators for subtelomeric defects are family history of mental retardation, prenatal onset growth retardation, postnatal poor growth/overgrowth, two or more facial dysmorphic features, one or more nonfacial dysmorphic features and/or congenital abnormalities^26,27. If the family history is positive for any of these conditions, subtelomeric analysis may be warranted.

In the future, it is expected that genome-wide screening will become routine as a diagnostic approach for detecting subtelomeric rearrangements and other genetic anomalies that contribute to IDD²⁸. This has far-reaching implications for families with a child with IDD. Nurses will be instrumental in helping families make decisions regarding potential genetic testing in affected and non-affected individuals. In particular, they will help families identify and address the ethical, legal and social issues associated with genetic testing.

Recurrence Risks

Another very important reason for nurses to construct and interpret pedigrees for IDD is that they can provide parents/caregivers of an affected child with information about the likelihood that another child in their family, or a child born from a future pregnancy, will also have IDD. Providing recurrence risks to families is included in the American College of Medical Genetics recommendations (Table1)⁵. If a specific genetic diagnosis is made, such as an autosomal dominant disorder, estimation of recurrence risk for IDD will be dictated by the identified mode of inheritance²⁹. However, if the cause of IDD is unclear, general estimates of having another affected child range from 2% to 14%. These estimates also apply to future pregnancies. A recent study of children born in Atlanta between 1981 and 1991 estimated recurrence risks based on the characteristics of the first affected child³⁰. The recurrence risk was 8.4% if the affected child was an isolated case of mental retardation. Corresponding figures for families who had a child diagnosed with isolated mild versus severe mental retardation were 7.1% and 4.7%, respectively. Although pedigree evaluation is part of the initial assessment of IDD, the American College of Medical Genetics stresses the importance of serial evaluations over time, indicating that the probability that a diagnosis of IDD is made increases 5% to 20% with return visits¹⁰.

NURSING IMPLICATIONS

There are now numerous opportunities for nurses to receive training in genetics. Readers are referred to the organizations listed in Table 2 for additional information. New graduates from BSN programs have most likely been educated in genetics through their coursework because of the established genetics competencies for nurses^7-9. In addition, it is now possible for nurses to prepare a "Genetics Nursing Portfolio" that uses an evidence-based approach to document their expertise in clinical genetics³¹. This is a new tool that is becoming increasingly important in terms of genetics certification by the Genetic Nursing Credentialing Commission, Inc. (GNCC)³¹.

The professional responsibilities outlined by the new "Essentials" document include an expectation for all registered nurses to be able to construct a three-generation family health history and construct a pedigree using standardized symbols and nomenclature⁹. Nurses will, therefore, become increasingly involved with these activities for IDD and other chronic disorders. This requires an understanding of the value of obtaining family history information. Nurses who care for children with IDD as part of their clinical practice will be aware that genetic factors are responsible for many cases of IDD. There may be recorded family history information in their patients' medical records. With access to tools such as "My Family Health Portrait," nurses can construct a pedigree. Given that there will always be time constraints, nurses can partner with parents/caregivers to complete the family history tool using the checklist. This information can be reviewed and verified during short segments of time at clinic visits and/or by phone interviews.

Constructing a pedigree will also help nurses identify families who may benefit from a genetic referral. Because genetic counseling begins by collecting family history information and constructing a pedigree, the nurse who has performed these activities will be assembling a multi-disciplinary team who will be directly involved with the care of the patient. Specialists qualified to provide genetic counseling include clinical geneticists, certified genetic counselors, or nurses trained in genetics. They can be located through the National Society of Genetic Counselors (www.nsgc.org/resourcelink.cfm). Nurses can help parents/caregivers by explaining the genetic counseling process, providing information about local and community support groups, and participating in any required follow-up.

Nurses who care for patients with IDD already answer parents'/caregivers' questions and help them prepare for the clinical examinations and laboratory evaluations required for diagnosis and follow-up. Therefore, they are the ideal health professionals to assess parents'/caregivers' psychosocial, cultural and educational background, and provide them with accurate and understandable information at the appropriate level. With access to tools that provide a graphical representation of a family's history, nurses can more easily explain a suspected pattern of inheritance and the possibility of genetic testing for at-risk family members. If genetic testing is suggested for diagnostic purposes, nurses will participate in the family's decision-making process and ensure that appropriate informed consent is obtained. Nurses are aware of spiritual factors, family dynamics and other situations that could be factors influencing a decision about genetic testing. Therefore, nurses will be able to assess the family's coping skills and refer them to the genetic resources that will be most helpful.

Nurses knowledgeable about genetics can play a central role in providing the information, education and support families need in order to deal with genetic issues related to IDD. A recent position statement issued by the International Society for Nurses in Genetics (ISONG) noted that: "Nurses, as the omnipresent health care provider, have a central role in providing information and support in the multiphase processes of genetic testing. With genetics knowledge, nurses can advocate, educate, counsel and support clients during the informed decision-making and consent process"³². This nursing role may perhaps be most important for families with IDD, who face the life-long challenges that accompany IDD.

TABLE 1. EVALUATION OF MENTAL RETARDATION: RECOMMENDATIONS OF A CONSENSUS CONFERENCE*

The individual with mental retardation, the family, and medical care providers benefit from a focused clinical and laboratory evaluation aimed at establishing causation and in providing counseling, prognosis, recurrence risks, and guidelines for management.

Essential elements of the evaluation include a three-generation pedigree: pre-, peri-, and post-natal history, complete physical examination focused on the presence of minor anomalies, neurologic examination, and assessment of the behavioral phenotype.

Selective laboratory testing should, in most patients, include a banded karyotype. Fragile X testing should be strongly considered in both males and females with unexplained mental retardation, especially in the presence of a positive family history, a consistent physical and behavioral phenotype and absence of major structural abnormalities. Metabolic testing should be initiated in the presence of suggestive clinical and physical findings. Neuroimaging should be considered in patients without a known diagnosis especially in the presence of neurologic symptoms, cranial contour abnormalities, microcephaly, or macrocephaly. In most situations, MRI is the testing modality of choice.

Sequential evaluation of the patient, occasionally over several years, is often necessary for diagnosis, allowing for delineation of the physical and behavioral phenotype, a logical approach to ancillary testing and appropriate prognostic and reproductive counseling.

*From: Curry CJ, Stevenson RE, Aughton D, et al. "Evaluation of mental retardation: recommendations of a consensus conference." Am J Med Genet. 1997;72:468-477.,

TABLE 2. SELECTED FAMILY HISTORY RESOURCES

Internet Sites
Alliance of Genetic Support Groups: www.geneticalliance.org American Medical Association: www.ama-assn.org/ama/pub/category/14399.html American Society of Human Genetics: www.ashg.org/genetics/ashg/educ/007.shtml Centers for Disease Control Office of Genomics and Disease Prevention: www.cdc.gov/genetics/ Family Village – A Global Community of Disability-Related Resources: www.familyvillage.wisc.edu Genetic Alliance: www.geneticalliance.org/ws_display.asp?filter=fhh GeneClinics: www.geneclinics.org GeneSage: www.genesage.com Genetics Home Reference: National Library of Medicine: ghr.nlm.nih.gov Gene Tests: www.genetests.org Genetic Education Center, University of Kansas Medical Center: www.kumc.edu/gec/ March of Dimes: www.marchofdimes.com My Family Health Portrait: www.cdc.gov/genomics/public/famhix/links.htm National Coalition for Health Professional Education in Genetics: www.nchpeg.org National Society of Genetic Counselors: www.nsgc.org/consumer/familytree/ Online Resource Center (Genetics Education and Counseling Program, University of Pittsburgh, Graduate School of Public Health, Department of Human Genetics): www.hgen.pitt.edu/counseling/resources.htm
Books
Bennett RL. The Practical Guide to the Genetic Family History. New York: Wiley-Liss, Inc.; 1999. Lashley FR. Clinical Genetics in Nursing Practice. New York: Springer Publishing, Inc.; 2005. Jenkins JF, Halsey Lea D. Nursing Care in the Genomic Era: A Case-Based Approach. Boston: Jones and Bartlett Publishers, Inc.; 2005. Halsey Lea D, Jenkins JF, Francomano CA. Genetics in Clinical Practice: New Directions for Nursing and Health Care. Boston: Jones and Bartlett Publishers, Inc.; 1998. Skirton H, Patch C. Genetics for Healthcare Professional: A Lifestage Approach. Oxford: BIOS Scientific Publishers Limited; 2002.

TABLE 3. PRIMARY PATTERNS OF HUMAN INHERITANCE*

Autosomal dominant	Autosomal recessive	X-linked dominant	X-linked recessive
Male-to-male transmission Condition seen in multiple successive generations Males and females affected Often see variability in severity of clinical disease expression Affected individuals may have late age of clinical onset Homozygotes may be more severely affected than heterozygotes Homozygous state may be lethal	Affected individuals usually just in one generation Sometimes see parental consanguinity Males and females affected May be mistaken for sporadic occurrence if small family size Symptoms often seen in newborn, infancy, or early childhood Disease may be more common in certain ethnic groups Often inborn errors of metabolism	Often lethal in males, so see a paucity of males in pedigree May see multiple miscarriages (because of lethality in males) Females usually express condition, but have milder symptoms No male-to-male transmission	Males affected Females may be affected, but usually much milder than males May be "missed" if paucity of females in family No male-to-male transmission

*From: Bennett RL. The Practical Guide to the Genetic Family History. New York: Wiley-Liss, Inc.; 1999. p. 15.