Challenges of diagnosis in fetal alcohol syndrome and fetal alcohol spectrum disorder in the adult.код для вставкиСкачать
American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 145C:261 – 272 (2007) A R T I C L E Challenges of Diagnosis in Fetal Alcohol Syndrome and Fetal Alcohol Spectrum Disorder in the Adult ALBERT E. CHUDLEY,* ANDREA R. KILGOUR, MEGHAN CRANSTON, AND MICHELLE EDWARDS Adults with fetal alcohol syndrome (FAS) and the subsets of individuals with attenuated phenotype subsumed under the umbrella term of fetal alcohol spectrum disorder (FASD) provide clinicians with a challenge. Compounding this, FASD is different from most genetic syndromes since a specific diagnostic biological test is not available. The diagnosis first needs to be suspected and confirmation requires a diagnostic assessment that is best carried out in the context of a multi-disciplinary team approach. There is surprisingly little research published on the prevalence, natural history, medical, and social complications relevant to adults with FASD. The evidence that is emerging suggests that this disorder is common, and that services to diagnose and treat these individuals are limited. Adults with FASD have a higher incidence of impairments in social adaptive and executive function, and a higher degree of psychopathology when compared to the general population. The impact of FASD has significant and serious effects on those affected with FASD, their families, and our communities. There is a need for improved access to diagnosis, and more research and evaluation of interventions currently in use. In this paper, we describe the current diagnostic criteria, the differential diagnosis, the prevalence, natural history, the behavioral and mental health consequences, medical and social management issues, and interventions for adults affected with this disorder. ß 2007 Wiley-Liss, Inc. KEY WORDS: fetal alcohol syndrome; fetal alcohol spectrum disorder; adult diagnosis; multi-disciplinary team assessments; dysmorphology; management; intervention How to cite this article: Chudley AE, Kilgour AR, Cranston M, Edwards M. 2007. Challenges of diagnosis in fetal alcohol syndrome and fetal alcohol spectrum disorder in the adult. Am J Med Genet Part C Semin Med Genet 145C:261–272. INTRODUCTION ‘‘Fetal alcohol syndrome is not just a childhood disorder; there is a predictable long-term progression of the disorder into adulthood, in which maladaptive behaviors present the greatest challenge to management.’’ Ann Streissguth, JAMA 1991 It was only in the last half century that the medical community and society were convinced of the physical and central nervous system effects of excessive alcohol use in pregnancy resulting in fetal alcohol syndrome (FAS) [Lemoine et al., 1968; Jones and Smith, 1973; Jones et al., 1973]. The diagnosis of FAS and its spectrum is a medical diagnosis, but its effects on society are far reaching [Streissguth, 1997]. At one end is the subset of individuals with FAS, and at the other end are those individuals with behavioral and cognitive deficits who exhibit minimal or no physical stigmata as a consequence of ethanolinduced prenatal brain injury including those conditions using the terms described by the Institute of Medicine (IOM) review of FAS [Stratton et al., 1996]. Within a decade of the original description of FAS [Jones and Smith, 1973; Jones et al., 1973], substantial behavioral and cognitive effects of prenatal alcohol exposure were seen in individuals who exhibited few sentinel features and or growth impairment. The Dr. Chudley is a Professor of Pediatrics and Biochemistry and Medical Genetics at the University of Manitoba. He is the Medical Director of the Genetics Program in Winnipeg. He has certifications in pediatrics, clinical genetics, and medical genetics. His clinical and research interests are in the areas of dysmorphology; the recognition, delineation and prevention of birth defects, including fetal alcohol syndrome, and fetal solvent exposure; the causes of mental retardation, developmental disabilities, and autism spectrum disorders; prenatal diagnosis; gene mapping; and gene discovery.He has been a consultant to the Manitoba and Alberta governments in issues related to Fetal Alcohol Syndrome Disorder (FASD) and he is a former member of Health Canada’s Public Health Agency National Advisory Committee on FASD. He is currently President of the Canadian College of Medical Geneticists. Dr. Kilgour is an Assistant Professor in Clinical Health Psychology at the University of Manitoba. She is a neuropsychologist with expertise in drug addiction, brain injury and the diagnosis of FAS in adults. Megan Cranston is a third year medical student at the University of Manitoba. She has research and clinical interests in FAS. Michelle Edwards is a fourth year medical student at the University of Manitoba. She has interests in community supports related to FAS in adolescents and adults. *Correspondence to: Albert E. Chudley, M.D., F.R.C.P.C., F.C.C.M.G., WRHA Program in Genetics & Metabolism, Departments of Pediatrics and Child Health, Biochemistry and Medical Genetics, University of Manitoba, Health Sciences Centre, FE 229 820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9. E-mail: email@example.com DOI 10.1002/ajmg.c.30140 ß 2007 Wiley-Liss, Inc. 262 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c Within a decade of the original description of FAS, substantial behavioral and cognitive effects of prenatal alcohol exposure were seen in individuals who exhibited few sentinel features and or growth impairment term fetal alcohol effects (FAE) [Rosett and Weiner, 1982; Sokol and Clarren, 1989] described this subset. This term is no longer in vogue [Aase et al., 1995], and has been replaced by other terms in the five diagnostic categories recommended by the IOM, an expert panel of FAS researchers and clinicians in the United States [Stratton et al., 1996]. These include FAS with prenatal alcohol exposure confirmed; FAS without prenatal alcohol exposure confirmed; partial FAS [pFAS]; alcohol-related birth defects [ARBD]; and alcohol related neurodevelopmental disorder [ARND]. Fetal alcohol spectrum disorder (FASD) is an ‘‘umbrella’’ term that includes all these diagnostic categories and describes the spectrum of ethanol teratogenesis in man [Koren et al., 2003; Sokol et al., 2003; CDC, 2005; Chudley et al., 2005]. FASD is not a diagnostic category and should be used only when referring to the whole collection of diagnostic terms. FASD is distinct from many genetic syndromes in that the disorder is potentially preventable. In affected adults, the implications and impact of the disease may involve employers, the criminal justice system, their partners, and their children. The term secondary disabilities, was introduced by Streissguth et al. [1996, 1997] in a longitudinal study of children and adults with FAS and FAE. Secondary disabilities are disabilities the client was not born with and that could be ameliorated through better understanding and appropriate interventions. Secondary disabilities were hypothesized to be the result of an interaction of behavioral and mental health pro- blems with an adverse environment. Streissguth et al. [1996, 1997] defined six secondary disabilities for all ages (mental health problems, disrupted school experience, trouble with the law, confinement, inappropriate sexual behavior, alcohol and drug problems) and three additional secondary disabilities that were exclusive to adults (dependent living, problems with employment, problems with parenting). Other studies have verified a common finding of these secondary disabilities in their study populations [Famy et al., 1998; Lemoine, 2003; Clark et al., 2004]. Common manifestations in adults may include depression, anxiety, or psychosis, sexual promiscuity, poor judgment, poor impulse control, restlessness, poor problem solving skills, resistance to change, difficulty forming lasting and meaningful relationships, gullibility and victimization, inability to understand or conform to social norms, and unemployment. There are several challenges for clinicians when considering an FASD related diagnosis in an adult. One challenge is educating primary care physicians about the recognition and possibility of FASD in an adult so that they may be referred for a diagnostic evaluation. Another challenge is the There are several challenges for clinicians when considering an FASD related diagnosis in an adult. One challenge is educating primary care physicians about the recognition and possibility of FASD in an adult so that they may be referred for a diagnostic evaluation. awareness of the secondary disabilities related to individuals who have been previously diagnosed as children, so that ARTICLE they can receive the help and intervention needed. The cognitively-impaired individual who has FAS likely has been diagnosed as a child and may have many social security services and supports in place, including residential care and vocational training. However, most FASD individuals have an invisible disease, since there may be no growth impairment and few, if any, dysmorphic features, and these individuals may not receive a diagnosis until adulthood. Although FAS is proclaimed to be one of the leading causes of mental retardation in North America, it is estimated that less than 50% meet the current definition of mental retardation [Streissguth et al., 1996, 1997]. There are a limited number of professionals who have the training and experience in a multi-disciplinary approach to making a FASD related diagnosis. Yet another challenge to the process of diagnosing FAS in adults is that reliable prenatal alcohol exposure history and informative birth records may be unavailable or non-existent. The IOM describes significant alcohol exposure as ‘‘a pattern of excessive intake characterized by substantial, regular intake or heavy episodic drinking’’ (the National Institute on Alcohol Abuse and Alcoholism defines heavy alcohol use as drinking five or more drinks per occasion on five or more days in the past 30 days) [NIAAA, 2000]. As further research is completed and as, or if, lower quantities or variable patterns of alcohol use are associated with ARBD or ARND, these patterns of alcohol use should be incorporated into the diagnostic criteria [Stratton et al., 1996]. However, if there is no documentation of alcohol intake in birth records, and/or the birth mother is not available for interview, the amount of alcohol intake remains unknown. We have advocated for a multidisciplinary approach to diagnosis, since these patients have a complex pattern of disabilities, and the assessments need to be comprehensive and involve the collaboration of a number of health professionals [Chudley et al., 2005]. Thus, a team is necessary in order to make an accurate diagnosis and ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c provide multi-dimensional recommendations for management. The assessment process begins with the recognition of need for diagnosis and ends with implementation of appropriate recommendations. The multidisciplinary diagnostic team can be geographical/regional, virtual, or can accept referrals from distant communities and be evaluated using telemedicine. The members of the team may vary according to the context of the diagnosis. The team could include knowledgeable physicians, psychologists, speech and language pathologists, social workers, and a coordinator. Clinical geneticists are key members of multidisciplinary diagnostic teams, who have unique training and skills in syndrome recognition. Multi-disciplinary teams work with community partners and resources to develop and implement management plans to maximize intervention for the affected individual. Our experience reveals that in many adults an important source of information may be from welfare agents, employers, vocational teachers, appointed guardians, parole officers, advocacy workers, and the like. Following the assessment, a report containing the recommendations should be generated that would be available to the affected individual, and those employers, advocates, and justice workers who may be involved in case management, guardianship, or mentoring. PREVALENCE AND MORTALITY There is limited information on the epidemiology and prevalence of FASD in adults. The full spectrum of prenatal alcohol effects is difficult to estimate since there are no reliable biological markers that readily define those affected, and therefore, estimates likely under-represent actual incidence and prevalence [Sokol et al., 2003]. The prevalence is related to the frequency of excessive alcohol use in pregnancy and thus will vary from population to population. For the subset of individuals affected with FAS, the prevalence in the United States is 0.2–2.0 cases per 1,000 births across various populations and using various methodologies [CDC, 2005]. The prevalence of FASD for children and adults in Seattle Washington, for the period 1975–1981 is estimated to be 9.1/1,000 [Sampson et al., 1997]. This is higher than the combined prevalence of common genetic disorders and birth defects such as Down syndrome and spina bifida. There are certain regions and ethnic groups in which the incidence for FAS is much higher. The reasons for these variable rates and the failure to have accurate prevalence determination are related to several factors including: * * * * Variable poverty rates between states or provinces and between countries (poverty is strongly associated with alcohol use before and during pregnancy and a high risk for FASD). Genetic and ethnic differences (three different alleles of the alcohol dehydrogenase [ADH2] gene: ADH2-1, ADH2-2, and ADH2-3 with differing levels of enzymatic activity which can alter the risk of prenatal alcohol effects). Lack of uniformly accepted diagnostic criteria for FAS in the past, and the need for diagnostic criteria for those who lack dysmorphic features in a high proportion of affected children and adults (ARND). Lack of knowledge, skill, training, and misconceptions among primary care providers [CDC, 2005]. There are no national statistics on mortality in adults affected by FASD. In children the mortality rate has been suggested to be 6%, and the all-cause mortality in siblings of children diagnosed with FAS is increased 530% compared to controls [Habbick et al., 1997; Burd and Wilson, 2004; Burd et al., 2004]. It is assumed that the mortality rate is high in FASD adults in light of the social chaos, drug dependency, and high incidence of mental health problems these individuals face. DIFFERENTIAL DIAGNOSIS AND CO-MORBIDITY There are several genetic disorders that could present with features mimicking 263 FAS or pFAS in children and adults [Chudley et al., 2005; Hoyme et al., 2005]. Most of these disorders can be differentiated from FAS by a detailed family and pregnancy history, alcohol exposure history, physical examination and chromosome analysis, and/or specific molecular testing. For those adults with FASD and particularly ARND, many other conditions can lead to impairments in cognitive function, memory, executive function, etc., and a thorough neuropsychological evaluation and a history of prenatal alcohol exposure is essential in arriving at an accurate diagnosis. Some FASD individuals may also have other genetic or mental health disorders that coexist independent from effects of prenatal alcohol exposure. For instance, an individual with Down syndrome may also exhibit some dysmorphic features, brain dysfunction, or brain injury from prenatal maternal alcohol exposure. It would be a difficult clinical task to attribute which proportion of physical findings and cognitive impairment results from the genetic syndrome, and which component is the result of the prenatal alcohol exposure. Nevertheless, clinicians need to be cognizant of the potential role of prenatal alcohol effects on the phenotype in adults with genetic syndromes. DIAGNOSTIC CRITERIA The diagnosis of FAS depends on the presence of the cardinal findings of dysmorphic facial features, evidence of brain dysfunction, and prenatal and postnatal growth deficiency in the presence of prenatal alcohol exposure [Clarren and Smith, 1978]. The diagnosis is best done by a multi-disciplinary team as there are several areas of evaluation required that no one discipline alone can provide [Chudley et al., 2005]. In the absence of characteristic growth impairment and facial dysmorphology, the diagnosis of pFAS or ARND might be considered assuming cognitive impairments. However, only FAS can be diagnosed without information on prenatal alcohol exposure. In individuals with cognitive and behavioral difficulties without facial 264 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c dysmorphology and the absence of maternal history of prenatal alcohol exposure, an FASD related diagnosis cannot be made with our current understanding and assessments. Evaluating the Face and Other Physical Findings Astley and Clarren [1996, 1997, 2000], using data from the Washington State Fetal Alcohol Syndrome (FAS) Diagnostic and Prevention Network (DPN) of clinics, developed the 4-Digit Diagnostic Code. The four digits in the code reflect the magnitude of expression of the four key diagnostic features of fetal alcohol syndrome in the following order: (1) growth deficiency; (2) the fetal alcohol syndrome facial phenotype, using the palpebral fissure length percentiles (Fig. 1), and the shape of the philtrum and upper lip (Fig. 2); (3) central nervous system damage/dysfunction; and (4) gestational alcohol exposure. The 3rd edition of the DPN 4-Digit Diagnostic Code Manual [Astley, 2004a] is available and is being used for diagnosis, screening, and surveillance efforts in all Washington State FAS DPN clinics. Modifications of the 4-Digit Code are being used in many clinics throughout North America for use in the diagnosis of children and adults. Table I illustrates how the 4-Digit Code can be integrated with the IOM Diagnostic categories. The sentinel facial features consist of short palpebral fissure lengths (pfl), a poorly formed philtrum and a thin vermilion border of the upper lip. Ideally and traditionally, a short pfl is considered to be less than 1.5–2 standard deviations (or approximately 10th centile and 2nd centile); for an adult this is typically pfl of less than 27 mm. We based this measurement on extensive experience with adults, as well as a study using three methods to evaluate the pfl; a clear plastic ruler, a slide precision caliper, and the photographic analysis using the software program available through the University of Washington DPN [Astley and Clarren, 1996]. The landmarks for pfl measurements are key in the evaluation (Fig. 1), and require training and practice. In our study of 50 adults (Canadian medical students) of mixed ethnic background, the mean and standard deviation of the pfl was 29.3 1.37 mm with the ruler and an almost identical finding with the computer photographic method [Cranston, 2006]. The pfl using the caliper measurements were consistently 0.5 mm longer when compared to the Figure 1. Landmarks used to measure the palpebral fissure lengths of both eyes. Identify the inner corner or endocanthion (en) and outer corner or exocanthion (ex) for each eye. The ex can be clearly seen if the patient is asked to gaze upward. Measure with a clear flexible ruler in the horizontal plane the length of each ex–en interval immediately below the eye, being careful not to touch the eye or eyelashes. Look at the eyes perpendicular to the pupil; looking at the side will give a false reading. Plot the result using an appropriate nomogram chart to identify the centile or standard deviation for each eye. (From Chudley et al., CMAJ, 2005 with permission.) ARTICLE two other tools. The normative data on adults published in Hall et al. , and used in the computer software package calculation for the standard deviation ranking from photographic measurements, are based on data from Farkas  who used calipers for the pfl measurements and were derived from Caucasian adolescents and adults from southern Ontario, Canada. Therefore, using the published graph standards when measurements involve the use of the ruler or the calculation from photographic computer program analysis gives a result that is about 1 standard deviation more than from our study and our clinical experience. To correct for this, one needs to add 1 standard deviation to the standard deviation calculated on the photographic computer program analysis or plotted on Hall et al. published graph. Using the published graph standards when measurements involve the use of the ruler or the calculation from photographic computer program analysis gives a result that is about 1 standard deviation more than from our study and our clinical experience. To correct for this, one needs to add 1 standard deviation to the standard deviation calculated on the photographic computer program analysis or plotted on Hall et al. published graph. The lesson here is that if one uses the published norms, the method or tool used to acquire the measurement needs to be the same as the method that generated the normative data! Clinically, we recommend either the use of the plastic clear ruler or the photographic ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c 265 tool, and correct for the 1 standard deviation difference in the published norms. Pfl do not change after 16 years of age. Data for pfl in adults from Clinically, we recommend either the use of the plastic clear ruler or the photographic tool, and correct for the 1 standard deviation difference in the published norms. other ethnic backgrounds have not been published. A poorly formed philtrum is defined as a 4 or 5 score on the lipphiltrum pictorial guide (Fig. 2), and a thin vermilion border of the upper lip is defined as a 4 or 5 score on the lip-philtrum pictorial guide, or a circularity score that is only used in conjunction with the photographic software program The evaluation of the philtrum and the vermilion of the upper lip in adults can be a challenge if the patients sport a moustache. The final rank score is derived from a ABC score obtained using the three sentinel facial features (Fig. 3). The growth ABC score and other tables are available from the 4-Digit Code manual [Astley, 2004a] and are also on the back of the lip-philtrum pictorial guide. There is some controversy concerning whether the dysmorphic features in FAS children persist into adulthood. Some are of the opinion that the sentinel features in classical FAS do Figure 2. Lip-philtrum pictorial guides; left, Caucasians, right, Black Americans. (Courtesy Dr. Susan Astley, University of Washington, Seattle, WA.) persist [Streissguth et al., 1991; Streissguth, 1994]. Others believe that the diagnosis of FAS and the expanded phenotype is most accurately done between the ages of 2 and 11 years [Stratton et al., 1996], due to changes with maturation. There are few published reports on dysmorphology in FAS adults. Streissguth et al.  assessed 61 adolescents and adults with FAS. They stated that ‘‘The characteristic facies of children became less distinctive TABLE I. The IOM Diagnostic Categories and the Corresponding DPN 4-Digit Code Rankings IOM nomenclature FAS (with confirmed exposure) Partial FASa (with confirmed exposure) FAS (without confirmed exposure) ARND (with confirmed exposure) a Growth 2, 3, or 4 1, 2, 3, or 4 2, 3, or 4 1, 2, 3, or 4 Face 3 3 3 1 or or or or 4 4 4 2 Braina Alcohol history 3 or 4 2, 3 or 4 3 or 4 3 or 4 3 or 4 3 or 4 2 3 or 4 Occasionally rank score of 2 for the brain for those less than age 6 years can be used in difficult cases or in whom no standardized scores are readily available, using clinical judgment) Modified from Chudley et al. . 266 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c ARTICLE hood, and should be considered reliable markers for possible prenatal alcohol exposure. Evaluating the Brain Figure 3. Chart located on back of the lip-philtrum guide to determine the ABC score for the three sentinel facial features to establish the rank score for the face. (Courtesy Dr. Susan Astley, University of Washington, Seattle, WA.) with increasing age, but that in many cases the eye anomalies, short palpebral fissures and abnormalities of the philtrum and lips remain useful diagnostic features in adolescents and adults.’’ The facial pattern of changes are what is expected during and after normal puberty as the face elongates, the mid-face and chin lengthen and grow outward (Fig. 4). Lemoine  re-contacted and re-examined 105 now-adult cases from his original report on 125 alcohol affected children [Lemoine et al., 1968] and noted that the facial anomalies had changed, ‘‘often with a large nose and large chin (contrary to the newborn); the statural and ponderal hypotrophy were attenuated; the microcephaly persisted significantly; the intellectual deficits persisted, as did the maladaptive behavior’’. Lemoine  did not report on the pfl on objective measurement nor on the philtrum or upper lip appearances. Our own experience suggests that the physical features in children with FAS persist into adult- There are several ways in which the brain in FASD needs a detailed evaluation, which is as critical as a proper evaluation searching for evidence of dysmorphic features. The Canadian and American guidelines for FASD assessment have recommended the evaluation of several brain domains [CDC, 2005; Chudley et al., 2005]. These domains include the documentation of structural, neurologic, and functional abnormalities. Structural Brain and Neurological Abnormalities The brain is vulnerable to the adverse effects of prenatal alcohol exposure through all three trimesters of the pregnancy, although different effects may be observed depending on the amount of alcohol consumed, the blood alcohol level achieved, the duration of exposure, and the stage of gestation during which alcohol is consumed. No specific anatomical region of the brain appears to be targeted, although malformations seen include migration abnormalities including Figure 4. Patient diagnosed with FAS as an adult. A: At age 5 years. B: At age 10 years. C: At age 19 years. ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c gray matter heterotopias or variable degrees of lissencephaly, abnormalities in the size, shape, and position of the corpus callosum, cerebellar vermis hypoplasia, hypoplasia of the basal ganglia and hippocampus, and microcephaly [Streissguth et al., 1991; Mattson et al., 2001]. Most individuals with FAS show no gross anatomical abnormalities on brain imaging. However, many may have neurologic damage, and exhibit seizures, soft neurological signs such as poor coordination and balance, and visual motor difficulties. Thus a careful neurological examination is warranted [CDC, 2005; Chudley et al., 2005]. Neuropsychological Assessments The Canadian guidelines [Chudley et al., 2005] recommend assessment of hard and soft neurological signs (including sensory-motor); brain structure (OFC, MRI scans, etc.); general intellectual ability (IQ); communication: receptive and expressive; academic achievement; memory; executive functioning and abstract reasoning; attention and adaptive behavior, social skills, and social communication. The assessment should include and compare basic and complex tasks in each domain, as appropriate. Although the domains are assessed as though independent entities, where there is overlap, experienced clinical judgment is required to decide how many domains are affected. A domain is considered ‘‘impaired’’ when on a standardized measure scores are two standard deviations or more below the mean, or there is a discrepancy of at least 1 standard deviation between subdomains. For areas where standardized measurements are not available, a clinical judgment of ‘‘severely abnormal’’ is made, taking into consideration that important variables, including age, mental health factors, social-economic factors, and disrupted family/home environment (e.g., multiple foster placements, history of abuse and neglect) that may affect development but do not indicate brain damage [Chudley et al., 2005]. On neuropsychological assessments, exposed individuals show deficits on tasks related to the function of the prefrontal cortex and hippocampus, characterized by deficiencies in executive functions, working memory, information processing, attention, and place learning [Mattson and Riley, On neuropsychological assessments, exposed individuals show deficits on tasks related to the function of the prefrontal cortex and hippocampus, characterized by deficiencies in executive functions, working memory, information processing, attention, and place learning. 1998; Mattson et al., 2001; Hamilton et al., 2003]. FAS adults, who do not have mental retardation and have an IQ in the normal range, exhibit clear deficits in measures sensitive to complex attention, verbal learning, and executive function [Kerns et al., 1997]. Recent work assessing functional memory in both adults and children with FAS and ARND show impairments in spatial working memory on functional MRI analysis compared to controls [Malisza et al., 2005]. Whether these findings are specific to FASD individuals and a potential tool in diagnosis has yet to be determined. Fagerlund et al.  studied the brains of adolescents and adults with FASD using magnetic resonance spectroscopy (MRS), and suggested that prenatal alcohol exposure appears to permanently alter brain metabolism in a long-standing or permanent manner in multiple brain areas. These findings agreed with previous findings from structural and functional studies. Most of the metabolic alterations involved changes in the glial cell pool rather than in the neurons. From the neuropsychological perspective, the most difficult diagnoses are those in which severe deficits are not 267 found across all diagnostic criteria. It is becoming more recognized that fullblown FAS will manifest with significant impairment across at least three domains of cognitive functioning [Chudley et al., 2005], including reduced general IQ, as well as at least two other areas mentioned below. Those individuals whose Full Scale IQ scores are below 70, and show impaired adaptive functioning may be diagnosed with mental retardation. However, many FASD affected individuals do not meet these severe criteria. The Committee on Substance Abuse and Committee on Children with Disabilities  recognized that cognitive, behavioral, and psychosocial manifestations of FASD may vary with age and current life circumstances and that each individual may display a somewhat different constellation of deficits. There is no neurocognitive profile specific to FASD, although some research [Greenbaum et al., 2002] is emerging that shows fairly consistent patterns. For example, Full Scale IQ may fall in the low average to average range, however, it is not uncommon for Performance IQ to be within normal limits, but observe significantly lower Verbal IQ. As well, when assessing academic achievement, word reading, and spelling may be within the normal range, however, mathematical skills tend to be considerably reduced when compared to age-matched controls. Evidence of significant impairment in three domains is necessary for diagnosis and, in terms of diagnostic code would be equated to a score of 3 or 4 in the 4-Digit Code depending on the severity. A score of 2 is reserved for those individuals with mild impairment that may or may not reflect brain dysfunction from prenatal alcohol exposure and would not normally lead to a diagnosis in any category of FASD. This is a conservative approach and the threshold that has been established may exclude some individuals that may be mildly impaired from prenatal alcohol exposure. Until there are tests that can better differentiate alcohol brain injury from other etiologies, establishing a cut-off is justifiable. Furthermore, individuals who score 3 or 4 on the brain assessment 268 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c may have other reasons for their impairment, and these could include genetic factors, brain injury from other pre- and post-natal environmental exposures, head injury, and drug abuse. MENTAL HEALTH DISORDERS AND THE ADULT WITH FASD Streissguth et al.  reported on an update of the secondary disabilities in adolescents and adults with FASD from their ongoing longitudinal study. The life span prevalence was 61% for Disrupted School Experiences, 60% for Trouble with the Law, 50% for Confinement (in detention, jail, prison, or a psychiatric or alcohol/drug inpatient setting), 49% for Inappropriate Sexual Behaviors on repeated occasions, and 35% for Alcohol/Drug Problems. Poor outcomes are increased two- to fourfold when diagnosis is after age 12 years and by unstable, poor home environments. In a British Columbia study, Clark et al. , showed a remarkably similar proportion of secondary disabilities in adults with FASD. Adults with FASD are at substantial risk for mental health illness. One study assessed 25 adults with FASD who had Full Scale IQ’s above 70 for psychopathology. These individuals underwent structured clinical interviews for psychiatric and personality disorders [Famy et al., 1998]. Drug or alcohol dependence was seen in 15 subjects, depression in 11 subjects, and psychotic disorders in10 subjects. The most common personality disorders were Avoidant in six subjects, Antisocial in four subjects, and Dependent in three subjects. Barr et al.  noted that young adults exposed to one or more binge alcohol episodes in utero had twice the odds of having substance dependence or abuse disorders and passive-aggressive and antisocial personality disorders compared to non-exposed control adults. The authors conclude that prenatal exposure to alcohol may be a risk factor for specific psychiatric disorders and traits in early adulthood, even in a nonclinical group, where a diagnosis of FASD was not present. There are few published reports on the risk of suicide in the FASD adult population [Kelly et al., 2000; Devlin, 2001]. It is unclear whether the risk for this is based on the postnatal environment or derived from the prenatal alcohol exposure and resulting brain damage [Kelly et al., 2000]. However, in light of the high incidence of mental illness, the social chaos, physical and mental abuse, poverty in which many of these individuals have come from or remain in, the high unemployment, the problems with the law with incarceration, and the high substance dependency and abuse rates, we suspect the risk of suicide is high. MANAGEMENT ISSUES FOR THE FASD ADULT A recent report on Town Hall Meetings related to FASD suggests that our systems of care provide supervised living arrangements for those who have sustained brain damage in accidents, but this does not extend to someone who has sustained brain damage prior to birth [Ryan et al., 2006]. Some adults who have a FASD do live independently with proper assistance, such as appropriate housing, vocational rehabilitation, and income support (e.g., Supplemental Security Income, Social Security Disability Insurance). Many adults with FASD are ineligible as their IQs often are within the normal range, which can disqualify them from support in many states and provinces despite their impairments. There was a recognized need for increased access to existing services, such as income support, housing, vocational rehabilitation, and developmental disabilities services. They often are perceived as ‘‘normal,’’ although their neurological problems result in functioning at levels that are far below normal [Ryan et al., 2006]. Perhaps the best accounts illustrating the impact on the FASD individuals, their families and the community are found in two classical publications on this subject authored by adoptive parents; Michael Dorris’s book The Broken Cord [Dorris, 1989] and Bonnie ARTICLE Buxton’s book Damaged Angels: A mother discovers the terrible cost of alcohol in pregnancy [Buxton, 2004]. Healthcare providers participating in the evaluation and treatment of FASD individuals and their families need to read these books. Both books give a personal account, the grief and hardship and the joy and success, of living with an FASD child and adult. The question of management issues for the adult with FASD highlights the need for the multi-disciplinary approach that includes a neuropsychological assessment. Such an approach will outline both the individuals’ deficiencies, as well as relative strengths. Therefore, individual programs can be tailored to meet the specific needs of each individual. FASD ADULTS AND THE LAW The diagnosis of a FASD related disorder is predictive of a high risk for trouble with the law and confinement [Boland et al., 2003]. The crimes vary from theft to murder. The typical pattern is nonviolent crime with repeated offences of failed compliance to parole conditions resulting in recidivism. It is unclear to what extent state, provincial and federal prisons house FASD individuals. Streissguth et al.  report that 60% of adolescents and adults in a sample of 253 FASD affected individuals, had some contact with the law and 35% had been incarcerated. The onset of trouble with the law started at a mean age of 12.8 years. Fast et al.  estimated that within a sample of young offenders remanded to a forensic psychiatric inpatient assessment unit, 23% were diagnosed as FASD. This study involved a highly select group who were remanded for further assessment, and does not represent the rate within the young offender population. Burd et al. , in a US study of 43 state or major cities’ corrections systems, distributed a questionnaire to determine the prevalence of FAS and ARND in the offender population, the availability of screening and diagnostic services to identify offen- ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c ders with FAS, and staff training needs related to FAS. Only four programs (7.4%) reported having access to diagnostic services for FAS in the corrections facilities. Of the 3,080,904 offenders, only one offender was reported to have a diagnosis of FAS. The authors concluded that correctional facilities have high, unmet needs to screen, identify, and treat offenders with FAS and ARND. In a similar study that surveyed Canadian corrections facilities, 13 of 148,797 offenders were reported to have a diagnosis of FAS [Burd et al., 2003]. This correlates to a prevalence rate of 0.087 per 1,000, below the estimated incidence rate of the American and Canadian population of FAS or FASD of 1–3 per 1,000 and 9.1 per 1,000, respectively. Clearly there are many that are undiagnosed FASD individuals. There is a need to efficiently and reliably identify at risk individuals and bring them into a diagnostic process. Some have advocated screening tools in prisons for this purpose [Burd et al., 2004]. Because of their disabilities, individuals with FASD do not typically respond to the standard cognitive therapy that is currently in place in the prisons and in the community [Boland et al., 1998]. Thus, standard programs do not work for these individuals. This mismatch between therapeutic modality and the abilities of the individual to respond to such treatment adds to the frustration experienced by both the affected individual and those attempting to assist him or her. In a correctional setting, for example, the affected individual may find their parole revoked or experience some other negative consequence for non-compliance, when, in fact, their cognitive limitations disallow what is considered ‘‘appropriate response’’ to treatment. Non-compliance may not be the issue. Unless there are better means to identify the FASD individual, and determine the true extent of the prevalence of FASD in our prisons, there will be no incentive to develop and adapt more effective intervention and substance abuse programs to address the needs of individuals with brain injury. THE FASD INDIVIDUAL AS A PARENT The manifestation of suboptimal parenting skills reflects the particular constellation of cognitive challenges the affected individual faces. The most cognitivelyintact parent has difficulties at times parenting their child(ren). Ideally, a parent displays consistency, patience, affection, but firm consequences for misbehavior. These characteristics can be a challenge for all. However, imagine a parent who experiences attention and memory deficits. How can they apply consistent responses to their child(ren)? If life-long deficits include reduced judgment and insight, the individual may not have the cognitive capacity to recognize poor judgment applied to parenting. FASD individuals frequently have children and the results show that to be successful as parents they require additional supports and resources. Streissguth et al.  has demonstrated that in her cohort of 253 FASD individuals, 17% were parents, at an average age of 18 years. Those who became parents had a higher rate of living in unstable homes, were more likely to have been homeless, and were more likely to have experienced domestic violence. A high proportion of these parents gave up parenting, or the children were apprehended by child protection services. An alarming 40% of the affected mothers had a history of drinking in the their pregnancy and 17% of their children had a FASD related diagnosis, suggesting that this group is at very high risk for having FASD affected children themselves. Recognizing these women as a high risk group should trigger an offer to refer the patient for counseling and support, and this may lead to an overall reduction in the chance of them having an alcohol affected child. There have been few studies that have demonstrated the effectiveness of treatment and prevention strategies in FASD. However, there are valid strategies for recognizing the atrisk mother in clinical practice [Loock et al., 2005], and, successful programs such as the network of clinics and prevention mentorship programs that 269 have been developed in the State of Washington; Astley, 2004b]. INTERVENTIONS The FASD adult needs to be looked upon as a neurologically impaired individual with a brain injury. They are vulnerable to physical violence and sexual abuse. They frequently get ‘‘lost’’ in the system, and have few family or friends who could advocate for their needs. They often have limited insights into of their lack of abilities and limitations, and frequently over-represent their capabilities to others and themselves. The ideal situation for an FASD individual is to have a mentor or proctor who offers structure and order, and functions as an ‘‘external brain’’, since most FASD individuals have poor judgment and adaptive skills. The ideal situation for an FASD individual is to have a mentor or proctor who offers structure and order, and functions as an ‘‘external brain’’, since most FASD individuals have poor judgment and adaptive skills. They would act as advocates and oversee their client’s daily living activities, assist in acquiring living accommodations, money management, offer advice and encouragement, remind them of their appointments or vocational duties, and assure their client’s safety and protection. With an appropriate multi-disciplinary assessment, the intensity of intervention required could match the actual need of the individual. The more severely affected individual may require 24-hr supervision, whereas less severe ARND manifestations may only require a situation with daily check-in and/or telephone contact with a mentor. Unfortunately, many FASD adults encounter difficulties with the law and experience a prison environment. 270 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c Although it is temporally structured, it is noisy, over stimulating, and requires that new coping skills be learned quickly. There are many opportunities to be misled by other offenders looking for people to participate in illegal activities. Alternative sentencing, having parole conditions that take into account their disability, and having mentors or proctors, will likely lower recidivism. More resources will have to be introduced to, or reallocated within, the social services systems to improve the outcome and quality of life for these individuals. ILLUSTRATIVE CASE Jennifer was born in a rural community. At 1 year of age she and two of her older siblings were apprehended by the Child Protection Agency in their community. She had experienced several placements in foster homes before being adopted at 3 years of age. She attended school regularly but struggled with academics and problems with behavior. She was held back in grade two, and had major difficulties with mathematics and language arts. She failed to complete most assignments, and often interrupted the teacher and was generally disruptive in the classroom. She was referred to a school psychologist at age 9 years and was diagnosed with attention deficit disorder and was placed in a modified school program. A stimulant medication was prescribed and she took this medication for 5 years with some benefit. During high school, she was placed in a vocational stream classroom, but dropped out of school in grade 11. She had few friends in school, and was considered to be violent and a troublemaker. Her adoptive parents noted that she often would not come home on weekends. She broke curfews, and would run away frequently for several days in a row. She struggled with alcohol and drug addiction. At 20 years of age she was hospitalized for a short period after being assaulted by her boy friend. At the age of 21 years she delivered a baby boy, who was placed for adoption. She could not hold a job for more than a few weeks, often being fired because of frequent absences and difficulties with co-workers. She depended on her parents for financial support. Her parents recognized that her life was chaotic and she was immature and was not able to cope with the challenges in her life. Contact with social services was made and a social worker suggested that she might be affected by FASD. A referral was made for Jennifer to be evaluated with the FASD Diagnostic team in their region. Detailed background information was obtained, and her parents were found to both have been alcoholics. Heavy prenatal use of alcohol by the birth mother was confirmed during all three trimesters of the pregnancy. Her birth parameters were normal, and apart from the neglect and suspected abuse she was otherwise healthy for most of her life. Physical and dysmorphology assessment confirmed normal height and weight, a head circumference at the 10th–25th centile, a normal neurological examination with mild fine motor deficits, short palpebral fissures (2.6 cm; <3rd centile), a smooth philtrum, and a thin upper lip (a score of 4 for both on the lip-philtrum pictorial guide). A comprehensive neuropsychological evaluation revealed an overall low average score on cognitive testing with a significant difference between verbal and non-verbal performance. Functional memory and attention was severely impaired, and she had impaired executive function and social adaptive abilities. A diagnosis of partial FAS was made and the diagnostic team referred her to the community FASD adult program for supportive living. She received counseling for her addiction, taking into consideration that she had cognitive impairments. She was connected with a mentor in the program who helped her understand the nature of her disability and assisted her with application for social assistance, budgeting, food allowance and enrollment in school upgrading and job training. Two years after the diagnosis and interventions, she was able to live on her own with ongoing assistance, she was drug free and she was working as a hair stylist in her community. ARTICLE CONCLUSIONS Ultimately, we believe a reliable, multidisciplinary team diagnosis is the first step in effectively understanding the issues and identifying the needs of the affected adult. The diagnosis can lead to a paradigm shift in attitude and perception towards the affected individual from one of a lazy, lying, obstinate and difficult individual or sociopath, to that of an individual who is neurologically impaired and who needs appropriate assistance, with specific management and treatment. Ultimately, we believe a reliable, multi-disciplinary team diagnosis is the first step in effectively understanding the issues and identifying the needs of the affected adult. The diagnosis can lead to a paradigm shift in attitude and perception towards the affected individual from one of a lazy, lying, obstinate and difficult individual or sociopath, to that of an individual who is neurologically impaired and who needs appropriate assistance, with specific management and treatment. Although a diagnosis made in an adult may not offer the same advantage of preventing the occurrence of secondary disabilities that is evident when a diagnosis is made in a young child, a diagnosis can offer hope and change lives. A diagnosis may mitigate progression or reduce secondary disabilities, provide an answer to the individual for his or her disabilities and failures, and improve their likelihood of being connected to interventions and services for FASD adults. ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c Steven Neafcy writes: ‘‘I was not diagnosed with FASD until I was 43 yrs old and not knowing the reasons for my actions was very frustrating. I was really a person who wanted to do good!! I could not understand what drove me to disappoint those I wanted to be proud of me. I was so lost! It was only after I was diagnosed with FASD that I realized my brain was like a fuse box on overload without the current flow that healthy brains have, to give me the chance to think before I acted and make a choice. This was taken away from me by the alcohol before I was born. Now where do I go from here? First it was important for me to realize the reason I had a short circuit. With this information I could pick up from that point and not keep bashing my head against the wall trying to be normal and function like those who don’t have brain damage. This is impossible! Now knowing this would I take advantage of this Knowledge? At first maybe so, but with a chance to begin where I am capable and achieve from that point can only better my life. Now I might have a damaged brain and be unable to make decisions, but by turning to my higher power, that being (God) would and could take over for me.’’ [Retrieved from: http://www.acbr. com/fas/]. Having advocates or mentors for FASD individuals can effectively fill the gap in services and supports. FASD adults who have had advocates have experienced increase in personal income, received direct services by being found eligible for existing programs in the system that they did not know how to access prior to the help, and they have become empowered to make changes in their lives [La Berge, 2004]. RESOURCES There are many excellent web sites on FASD that also link to other resources in print, in video format or on the worldwide web. These are just a few of the sites that we recommend for clinicians and families. FASD websites: www.ccsa.ca Canadian Centre for Substance Abuse. Excellent site with FAS Tool kit and a section on adults affected by FASD. www.fasdconnections FASD Connections—Serving Adolescents and Adults with FASD. www.fasworld.com Contains many links to useful sites. www.fasstar.com Teresa Kellerman’s of the FAS Family resource center of Tucson Arizona. come-over.to/FASCRC/ FAS Community Resource Center Information about FAS and FASD. http://depts.washington.edu/fadu/ Fetal Alcohol Drug Unit (Dr. Ann Streissguth’s research site on FAS at the University of Washington, Seattle). http://depts.washington.edu/ fasdpn/htmls/whatisfasdpn.htm FAS Diagnostic and Prevention Network (Dr. Susan Astley’s site at the University of Washington, Seattle). The 4-Digit Code manual is available from this site. http://www.cdc.gov/ncbddd/fas/ default.htm Department of Health and Human Services. CDC. 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