Genetics, mental retardation, and the forging of new alliances^†

“Mental retardation is not something you have, like blue eyes or a bad heart, nor is it something you are, like short or thin. It is not a medical disorder or a mental disorder … . Mental retardation reflects the ‘fit’ between the capabilities of individuals and the structure and expectations of their environment.” [American Association on Mental Retardation, 1992]

INTRODUCTION

There is general agreement that between 1% and 3% of people in the United States, an estimated four million individuals, meet the cognitive and functional criteria for mental retardation [McLaren and Bryson, 1987; Massey and McDermott, 1995]. Most of those affected have mild intellectual retardation resulting from a multitude of diverse causes, both congenital and acquired. Genetic factors play an important role in the etiology of mental retardation at all IQ levels [Matalainen et al., 1995; Rutter et al., 1996]; and with the current exponential growth in genetic information comes a potentially concomitant growth in our understanding of the causes, treatment, and prevention of developmental disabilities. Educators, psychologists, and other nonmedical professionals who make up the mental retardation field are uniquely poised to play a role in the identification of individuals with genetic disorders, the investigation of behavioral phenotypes, and the implementation of practical applications of genetic research. However, steeped in an historical rejection of past eugenics practices, they have been slow to embrace the “new genetics” and continue to be cautious about its future implications [Kuna, 2001].

Educators, psychologists, and other nonmedical professionals who make up the mental retardation field are uniquely poised to play a role in the identification of individuals with genetic disorders, the investigation of behavioral phenotypes, and the implementation of practical applications of genetic research. However, steeped in an historical rejection of past eugenics practices, they have been slow to embrace the “new genetics” and continue to be cautious about its future implications.

EUGENICS AND THE EVOLUTION OF THE MENTAL RETARDATION FIELD

During the first two decades of the 20th century, a number of factors converged to fuel a growing public and professional view that immorality, crime, poverty, and other social ills in the United States were the direct outcomes of inherited mental deficiency. The Kallikak Family [Goddard, 1912] and similar published studies chronicled the “inheritance” of moral degeneracy and criminality in multiple generations of families with low intelligence. Many prominent scientists of the era were convinced that mental deficiency and its associated social effects could be boiled down to simple Mendelian traits. The pervasive view of the time negated environmental determinants of intelligence and behavior and assumed an all-powerful and intractable genetic etiology. By the 1920s, efforts toward the prevention of mental deficiency focused almost exclusively on identifying and removing affected individuals from society, as well as controlling their reproductive destinies [Scheerenberger, 1987]. Many thousands of individuals with mild mental retardation were imprisoned in the large, isolated institutions that thrived during that era. It is estimated that over 60,000 people in the United States underwent involuntary sterilization as part of legalized efforts to eliminate inherited mental deficiency from society.

Though this period of eugenic hysteria lasted less than a quarter of a century, its consequences were not easily forgotten. The subsequent backlash against eugenics and the medical model of mental retardation ultimately spawned a field that in many ways became the antithesis of the one it rejected; genetic theories about etiology were replaced by social and environmental ones, leading to optimistic predictions about the prevention of mental retardation through educational interventions

The subsequent backlash against eugenics and the medical model of mental retardation ultimately spawned a field that in many ways became the antithesis of the one it rejected; genetic theories about etiology were replaced by social and environmental ones, leading to optimistic predictions about the prevention of mental retardation through educational interventions.

; and the dehumanization of people with mental retardation was replaced by a focus on individual rights and human diversity. The desire of the “new” mental retardation field to distance itself from its past was so complete that to this day, it harbors a deep-seated mistrust of the medical field in general, and of modern genetic services in particular [Smith, 1994].

TWO FIELDS, TWO PERSPECTIVES

Beginning in the 1930s with the growing rejection of eugenics practices, the genetics and mental retardation fields in the United States evolved along separate paths, engaging professionals with different backgrounds and philosophies, and with remarkably little cross-fertilization despite their common interest in developmental disabilities. In 1994, Hodapp and Dykens described the genetics and mental retardation fields as “two cultures” working in mutual isolation, with each side having little understanding of the views and accomplishments of the other.

In 1994, Hodapp and Dykens described the genetics and mental retardation fields as “two cultures” working in mutual isolation, with each side having little understanding of the views and accomplishments of the other.

On one side are medical professionals who tend to discuss mental retardation in the same breath as an upslanted eye, a cleft palate, and other tangible traits when describing a syndrome's associated features. On the other side are nonmedical professionals who, having long ago thrown the baby out with the eugenics bath water, view mental retardation as a complex social and behavioral construct rather than an inherent physiological characteristic. In the genetics culture, the work-up of a child with mental retardation is aimed at identifying the etiology of the disability, in the same way that one attempts to track down the underlying cause of short stature or a congenital heart defect. The benefits of finding an etiology seem self-evident to genetics professionals and include recurrence risk assessment, anticipatory medical guidance, and parental support [Curry et al., 1997]. To those working on the front lines of education and behavior management, however, etiology is perceived as irrelevant and, until recently, offered little in the way of practical information to address the life needs of children and adults with mental retardation.

Another major difference between the genetics and mental retardation fields relates to the way they conduct behavioral research [Hodapp and Dykens, 1994]. Research within the genetics culture is done almost exclusively on groups of people with the same etiological diagnosis, with little attention paid to differences in functioning within the group. As such, a genetics researcher might include a severely affected male with fragile X syndrome in the same study as one who has only mild mental retardation. This approach seems illogical to professionals in the mental retardation field, who are more concerned with the functional consequences of disability than with its etiology. Behavioral research in the nonmedical culture is done on groups of individuals with similar levels of cognitive and functional impairment, regardless of etiology. Using this approach, a person with Down syndrome and one with Prader-Willi syndrome who have similar IQs might be paired together in a research study, even though these syndromes differ markedly in associated cognitive profiles, maladaptive behaviors, and medical implications. Medical publications about genetic syndromes often focus on detailed descriptions of clinical abnormalities in those affected. Many within the mental retardation field view such reports as demeaning, essentially reducing the individual with a syndrome to the sum of his dysmorphic parts. Even the terminology used in medical and genetics journals is at odds with the “people-first” language [Taylor, 2002] currently embraced by the mental retardation field, adding to further misunderstanding.

As a result of the schism between the genetics and mental retardation fields, affected individuals and their families have so far been unable to benefit from a cohesive approach that ties in advances from both biomedical and functional research on their disabilities. This is evident when a mother, armed with practical literature about her daughter's diagnosis of Angelman syndrome, arrives at a school meeting to face a group of education professionals who have never heard of the disorder and consider it irrelevant to their work. It is also true in the medical setting when a parent is met by a physician who can describe each abnormal physical feature in her toddler with Williams syndrome, but who offers little insight into his future educational needs or abilities. Clearly, each of the two cultures holds a piece of the puzzle, but without collaboration, a comprehensive approach toward mental retardation research and habilitation cannot be achieved.

Clearly, each of the two cultures holds a piece of the puzzle, but without collaboration, a comprehensive approach toward mental retardation research and habilitation cannot be achieved.

DIAGNOSTIC CONFUSION

The mental retardation field, particularly special education, has historically paid little attention to etiological diagnoses. Psychiatric and other behavioral diagnoses predominate in the educational setting and are considered important for determining eligibility for services and program placement [Simon and Finucane, 1998]. Psychiatric diagnoses are based upon observed patterns of human behavior that for many decades have been described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) [American Psychiatric Association, 1994]. In most cases, and for all the developmental disorders, psychiatric diagnoses are based solely on whether a person meets the criteria defined in the DSM-IV, regardless of the underlying cause.

The behavioral nature of psychiatric diagnoses is no more apparent than in the collection of symptoms described as Pervasive Developmental Disorders (PDD), also known as autistic spectrum disorders. The DSM-IV categorizes these disorders as being manifested by abnormalities in communication and socialization, with restricted patterns of behavior and interests. “Rett Disorder” is specifically defined as one of the PDDs, because affected females meet the criteria for autism but have a distinct and characteristic developmental course. Rett syndrome was initially included in the DSM- IV because it was defined behaviorally, in the absence of obvious physical pathology or a known underlying etiology. Now that the genetic basis for Rett syndrome has been determined [Amir et al., 1999], it will presumably no longer be considered a psychiatric diagnosis, and like other behavioral disorders of known etiology, will not be included in future revisions of the DSM. In addition to many genetic syndromes, most notably fragile X, tuberous sclerosis, PKU, and isodicentric chromosome 15, the molecular hunt for autism genes has uncovered linkage to at least nine autosomes, as well as the X chromosome [Liu et al., 2001]. This underscores the high degree of etiological heterogeneity in autistic spectrum disorders. Once a child is diagnosed as having autism or a related behavioral condition, however, parents and nonmedical professionals often fail to search for an etiological diagnosis in the mistaken belief that they already have one.

Unlike etiological diagnoses, most psychiatric diagnoses are not mutually exclusive. This can lead to a potentially confusing situation among people with developmental disabilities who often manifest symptoms consistent with more than one psychiatric disorder. The recent trend toward identifying etiological diagnoses, such as genetic mental retardation syndromes, has resulted in further misunderstanding, particularly in the school setting. For example, it would not be unusual for the school records of a 10-year-old student with Smith-Magenis syndrome to contain the following DSM-IV diagnoses: mental retardation, attention deficit disorder, pervasive developmental disorder—not otherwise specified, impulse control disorder, and oppositional defiant disorder. These diagnoses might support the student's need for certain school services, such as a one-to-one instructional assistant and placement within a highly structured “autistic support” classroom. However, there is often confusion within the school setting about the true meaning of these psychiatric labels, which in this case essentially describe the behavioral phenotype of Smith-Magenis syndrome [Dykens and Smith, 1998]. Parents and school personnel often question how a child could be so unfortunate as to be born with several different disorders, not realizing that the child actually has only one underlying condition, Smith-Magenis syndrome, which has resulted in a pattern of behaviors that fit into several different psychiatric categories. Such confusion is remarkably widespread and illustrates the mental retardation culture's recent struggle to incorporate etiology into its existing behaviorally based psychiatric diagnostic system.

Behavioral and etiological diagnoses serve distinctly different purposes. An etiological diagnosis can answer important questions about the genetic implications of a disabling condition and its associated clinical symptoms. Above all, it provides the fundamental answer to a parent's question: Why is my child different? In recent years, this answer has allowed access to a growing body of syndrome-specific literature on educational, behavioral, medical, and therapeutic interventions. However, an etiological diagnosis cannot predict the degree to which an affected person will manifest a syndrome's behavioral and cognitive features. By contrast, psychiatric diagnoses pinpoint expressed patterns of behavior in an individual, regardless of the etiology. These diagnoses can be crucial in establishing a person's eligibility for educational and therapeutic services, and they also guide decisions about educational interventions and pharmacological treatment of behavioral symptoms. For example, Ritalin is not prescribed to treat fragile X syndrome, but it is often used successfully to treat attentional disorders in children with this condition [Hagerman, 1999]. Similarly, an adult whose anxiety disorder is related to Williams syndrome [Udwin, 1990] might still benefit from medications used to treat anxiety in people who do not have the syndrome. The same holds true for non-medical therapies. A child whose autism is associated with an isodicentric 15 chromosome abnormality [Rineer et al., 1998] may still benefit from educational interventions developed for autistic children who do not have isodicentric 15. Once again, the genetics and mental retardation cultures have useful information to gain from each other, but it is only through collaboration that the current diagnostic morass can be resolved.

UNDER-DIAGNOSIS OF GENETIC MENTAL RETARDATION SYNDROMES

Although young children with developmental delay make up a significant percentage of patients seen by clinical geneticists, they represent only a small percentage of the total population of people with mental retardation. With over four million affected adults and children in the United States, their numbers alone tell us that most have never had a comprehensive etiological evaluation, or even routine genetic testing such as karyotyping and fragile X analysis. A lack of awareness in the medical community about the utility of genetic diagnostic services results in under-referral of patients for genetic evaluation, even when these services are widely available [Hayflick et al., 1998]. For many years, the genetics field has made efforts to educate the medical community about the importance of referring patients for clinical genetics services. These efforts have mostly focused on primary care physicians, particularly pediatricians, who act as the gatekeepers to specialty referral within the current healthcare environment. Surprisingly, though, there has been very little effort made to involve nonmedical professionals from the mental retardation field in the identification and referral process, even though they spend far more time with disabled children than do medical personnel.

Surprisingly, though, there has been very little effort made to involve nonmedical professionals from the mental retardation field in the identification and referral process, even though they spend far more time with disabled children than do medical personnel.

Special educators are potentially an ideal group to target for a genetics awareness project because they have long-term contact with numerous families and children at risk for genetic causes of mental retardation. More than any other professionals, educators are likely to establish an ongoing rapport and trust with the families and children they serve. Because of their involvement with children over extended periods of time, they are especially apt to recognize particular cognitive and behavioral profiles that are increasingly being associated with genetic mental retardation syndromes. Educators are also in an excellent position to follow up on referrals made for genetic services because of their daily contact with families over the course of a school year.

Despite these many advantages, the formal training of education professionals over the past four decades has not included an emphasis on etiological subgroups of children with developmental disabilities. Such professionals are not only uninformed about how and where to refer students for genetic evaluation but, more critically, about why etiology is important in the first place. Teachers working with students who have genetic syndromes consider these diagnoses, at best, only minimally relevant to their work; they often do not seek out syndrome-specific resources that might offer useful, practical information to help them in their work. Additionally, most teachers know very little about the many specific genetic syndromes associated with mental retardation, and they are unable to attach significance to even the most obvious signs in children who should be referred for genetic evaluation.

Largely overlooked by the genetics community and trained within a culture that has historically ignored, and even opposed, the concept of etiology, special education professionals represent a major untapped resource for genetics referral and research. There are approximately 20,000 special educators teaching children with developmental disabilities in the United States, as well as an additional 5,000 graduate and undergraduate students with an interest in special education

There are approximately 20,000 special educators teaching children with developmental disabilities in the United States, as well as an additional 5,000 graduate and undergraduate students with an interest in special education.

(Council for Exceptional Children (CEC), 2002, (1110 North Glebe Road, Suite 300, Arlington, VA 22201)). With today's emphasis on inclusion, an increasing number of regular education teachers also count children with intellectual disabilities among their students, as do numerous other education professionals, such as psychologists and school nurses. School personnel routinely refer students for speech, occupational, and physical therapies, as well as for psychiatric and neurological evaluations. A teacher who suspects that a student is having seizures in school would not hesitate to encourage the child's parents to pursue a neurological work-up; nor would it be unusual for a school psychologist to recommend a psychiatric evaluation for a child with ADHD who might benefit from medication. Because their training has not included an emphasis on etiology, however, education professionals rarely recognize that a child with mental retardation of unknown cause should be referred for a genetic evaluation. Like most workers in the mental retardation field, school staff continue to think of genetics, if they think of it at all, as an exotic research-based science that has little bearing on their practical work with special education students.

GENETIC SYNDROMES AND BEHAVIORAL RESEARCH

Kastner et al. [1994] pointed out in reference to health care among people with mental retardation that “Progress…is hampered by the fact that for many low incidence conditions, the etiology, natural history, and optimal treatment have yet to be characterized”. Similarly, a lack of awareness among nonmedical professionals with regard to specific genetic diagnoses has hampered improvements in educational interventions and habilitation. Upon surveying professional journals in the mental retardation field, Hodapp and Dykens [1994] found only a handful of research articles focused on behavior and learning in people with genetic syndromes. With the exception of Down syndrome, mental retardation researchers have traditionally been more interested in studying individuals grouped by level of impairment (mild, moderate, severe mental retardation) than by etiology. The converse is also true, and behavioral research conducted within the genetics culture is almost exclusively done on homogenous etiological subgroups. The authors concluded that a lack of cross-fertilization between researchers in the two fields has hindered the investigation of behavioral and cognitive phenotypes in people with genetic syndromes.

Down syndrome is among the very few diagnoses that has been studied extensively as a specific etiology by nonmedical researchers in the mental retardation field [Dykens et al., 2000]. Thousands of articles and books have been published on the disorder, including many that detail specific developmental patterns and educational strategies. Families and educators have a wealth of practical resources to draw upon when working with students who have Down syndrome. The genetics community has likewise been able to benefit from decades of behavioral research in Down syndrome to enhance its own investigations into molecular correlations with the clinical phenotype, including the predisposition to Alzheimer disease [Zigman et al., 1995].

A more recent example of successful collaboration between the genetics and mental retardation fields is illustrated by work on fragile X syndrome. Since 1985, hundreds of articles have documented the clinical phenotype, approaches to behavioral and educational management, the impact on the family, psychopharmacological interventions, and other practical issues in fragile X syndrome [Hagerman and Cronister, 1996]. Educators, therapists, and psychologists have made significant contributions to this body of literature, and publications have appeared in both medical and nonmedical journals. Dozens of books and pamphlets geared toward families and education professionals have also been widely disseminated, making fragile X syndrome one of the most extensively studied and documented causes of mental retardation.

To a lesser extent than in fragile X and Down syndromes, the publication of behavioral research and practical literature about Williams, Smith-Magenis, Rett, Prader-Willi, and a handful of other causes of mental retardation has also grown steadily over the past decade. Still, as long as most of those affected by specific syndromes remain undiagnosed, researchers can only examine the tip of the iceberg. They continue to miss out on an entire population of people from whom they could gain valuable insights into prevalence, natural history, and the “outer limits” of the clinical phenotype. Patients who make their way to the genetics clinics tend to be young and affected by obvious physical and behavioral abnormalities. This ascertainment bias skews researchers' perceptions of syndromic characteristics, particularly behavioral phenotypes. For all but a few syndromes, our understanding tends to be limited to “snapshots” of reported cognitive and behavioral features, most of which have not been rigorously researched in the context of matched peers with mental retardation, and which may or may not be syndrome-specific at all IQ levels [Simon et al., 1995]. Early descriptions of Smith-Magenis syndrome, for example, painted a generalized picture of severe self-injurious behaviors when, in fact, some of these behaviors may be age-related and time-limited [Finucane et al., 2001]. Many young boys with fragile X syndrome meet the DSM-IV criteria for autistic spectrum disorders [Bailey et al., 1998]. However, adolescents and adults with fragile X tend to more socially engaged than they were in early childhood and may no longer exhibit behaviors consistent with a pervasive developmental disorder [Hagerman et al., 1986]. Developmental and medical problems are often the most pressing issues for young children with a 22q11.2 deletion; yet major psychotic disorders, including schizophrenia and bipolar disorder, begin to emerge in a quarter of such patients into late adolescence and adulthood [Murphy et al., 1999]. What is the long-term outlook for children with genetic mental retardation syndromes? Researchers occasionally catch glimpses into the far end of the crystal ball when they serendipitously identify the affected parent of a newly diagnosed child [McDonald-McGinn et al., 2001]. Still, clinical, behavioral, and cognitive research, where researchers gain a solid understanding of a syndrome's natural history based on an N greater than a handful, is still lacking for most disorders. By cultivating connections with the mental retardation world, genetics professionals will be better able to accurately characterize syndromes across the full spectrum of age and severity.

DISCUSSION

For the first time in many decades, the genetics and mental retardation fields are now at a critical intersection. The growing interest in behavioral phenotypes is evidenced by the steady increase over the past few years in the number of genetics publications on behavioral and cognitive research. The mental retardation field has also begun to depart from its long-standing aversion to etiology; its major professional organization recently published an unprecedented special journal issue devoted to genetic mental retardation syndromes [American Association on Mental Retardation, 2001]. More so than at any other time over the past four decades, there is now an opportunity to create alliances between the two fields that may carry future mental retardation research in new and fruitful directions.

The importance of genetic support groups in fostering these alliances cannot be overstated. The mental retardation field's recent, tentative interest in genetics is motivated in part by pressure from families of individuals with diagnosed syndromes. School districts and social service agencies find themselves scrambling for information about genetic syndromes when faced with parents eager to implement practical applications of behavioral research. Information disseminated by syndrome-specific support groups has become increasingly sophisticated in recent years, relying heavily on established research by prominent experts in both medical and nonmedical fields. Through their publications and national conferences, these groups bring together experts from diverse backgrounds around a common theme, and their professional advisory boards offer unique opportunities to establish multidisciplinary collaborations. The group members themselves are highly motivated to participate in research, with a vested interest in increasing public awareness about low incidence conditions. The efforts of genetics professionals in helping to establish such groups and sustaining their activities are rewarded in the long-term by mutual collaboration between families and professionals.

The genetics community can also take an active role in promoting new connections with the mental retardation field by encouraging the publication of syndrome-based behavioral and educational research in clinical genetics journals.

The genetics community can also take an active role in promoting new connections with the mental retardation field by encouraging the publication of syndrome-based behavioral and educational research in clinical genetics journals.

Similarly, genetics professionals need to become familiar with mental retardation and special education journals, looking for opportunities to publish practical information that will dispel misconceptions about genetics while inviting potential collaborations [Finucane, 1995]. Topics related to genetics are still rarely included at major professional conferences in the mental retardation field, and the genetics community needs to establish a more visible presence at these meetings. There may also be a direct role for genetic counselors within special education settings in both the identification and ongoing support of people with genetic syndromes [Finucane, 1991]. These efforts may ultimately result in collaborations between the genetics and mental retardation fields that will expand and enrich our understanding of developmental disabilities.