The importance of differential diagnosis in neurodevelopmental disorders: Implications for IDEIA
These disorders develop over time and are associated with a wide variation of mental, emotional, behavioral, and physical features. Commonly known NDDs include autism spectrum disorders, cerebral palsy, attentiondeficit/ hyperactivity disorder (AD/HD), communication, speech, and language disorders, and genetic disorders such as fragile X syndrome (FXS) and Down syndrome (Reynolds & Goldstein, 1999). These various disorders, at symptom level, seem to share similar behavioral symptoms and diagnostic criteria; however, in the current version of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text-Revision (DSM-IV-TR), diagnostic criteria preclude the comorbid diagnosis of multiple disorders such as autism and AD/HD. This is a significant limitation in our current diagnostic criteria, as symptoms frequently overlap and best practice treatment suggestions may differ depending on one’s presentation.
This issue has been recognized in the recent revisions of the DSM-IVTR and is reflected in the proposed changes of the DSM-V. A new cluster of NDDs is proposed, which includes six categories: Intellectual Developmental Disorders, Communication Disorders, Autism Spectrum Disorders, Attention Deficit/Hyperactivity Disorder, Learning Disorders, and Motor Disorders. This new cluster has eight main features, highlighting the characteristics of deficits/ delays in “maturationally-influenced” psychological features, cognitive impairment, genetic influences, and overlap amongst the NDDs (Rutter, Kim-Cohen, & Maughan, 2006). The recognition of the prevalence of comorbidities in this cluster is important, especially for school psychologists, in order to gain a more complete and comprehensive insight into a child’s array of capabilities and deficits without being limited by the possibilities of exclusion due to outdated diagnostic criteria. Especially since these disorders often overlap, differential diagnosis is necessary to provide appropriate services. A differential diagnosis is a systematic method of diagnosis used to identify the presence of a disorder where multiple alternatives may be possible. Where once our diagnostic manuals (DSM-IVTR) precluded comorbid diagnoses of disorders such as autism and AD/HD, this exclusionary criteria is no longer present in the proposed DSM-V. This is the recognition that although symptoms may overlap, a child with autism and AD/ HD is distinctly different from a child with autism alone; thus, may require different intervention services.
School Psychologists’ Role as “Diagnosticians and First Responders”
This new approach to the conceptualization of NDDs will change the way we understand and define NDDs, their varying characteristics, and the way in which we diagnose such conditions. Psychologists in general, and school psychologists in particular, are moving toward a more treatmentfocused approach (i.e., Response to Intervention), which is of importance to school psychologists who are on the “front lines” providing intervention services and developing behavior intervention plans for students. Additionally, school psychologists still hold a primary role in the assessment of children. The National Association of School Psychologists’ (NASP) position statement on school psychologists’ role in assessment states that, “School psychologists engage in assessment to promote academic competence and mental health for all children…NASP endorses science-based assessment practices that are tailored to the needs and assets of individuals, groups, and systems.” Differential diagnosis of NDDs, or of psychopathology in general, is considered a science-based practice and essential due to shared presentation, and at times, etiology of disorders.
Diagnostic and eligibility decisions are high-stakes determinations that substantially impact the lives of students and their families. By recognizing the overlap of NDDs, school psychologists can better serve their clientele. In particular, understanding the categories of the Individuals with Disabilities Education Improvement Act (IDEIA) and which category best describes the presenting symptoms of each student is critical. For example, a student with comorbid autism and AD/HD may be better served as a student identified as Other Health Impaired (OHI) versus a student with Autism or an Intellectual Disability (ID). As school psychologists we can inform these decisions through a comprehensive, differential diagnostic assessment of presenting problems and provide a scientifically-supported plan of action.
There is also a push for earlier identification as early intervention is one of the keys to success for young children with NDDs. Research has demonstrated the immense benefits of intervention during the first three years of life for children with disabilities, and for some disabilities (i.e. autism) research suggests that amelioration of symptoms or even prevention of the disorder is plausible given the detection and treatment of individuals before the full disability develops (Dawson, 2008). In order to provide the most appropriate and effective treatments, special considerations must be taken when assessing children at young ages (Meisels & Atkins- Burnette, 2000). School psychologists working with children during early childhood have the opportunity to be “first responders” by facilitating the link between proper identification and intervention. One of the most important aspects of a comprehensive assessment is to differentially diagnosis among disorders that share common symptoms. As stated previously, children with NDDs represent a very heterogeneous population, which suggests that having a common diagnosis does not always imply the same presentation of symptoms or the same response to treatment efforts (Schwartz, 2008). Therefore, differential diagnosis is imperative as similar behavioral manifestations may exist across disorders and similar behaviors may manifest differently within a disorder. By understanding the commonalities and differences within NDDs, school psychologists can appropriately differentiate among them and implement the most effective interventions to address the unique needs of the child.
The Case of Fragile X Syndrome
An illustration of this new conceptualization of comorbidity and differential diagnosis and implications for IDEIA classification is fragile X syndrome (FXS). Within NDDs, FXS presents a helpful model for exploring the importance of differential diagnoses in schools in making eligibility and classification decisions. Fragile X syndrome is a single-gene disorder responsible for the largest number of heritable cases of intellectual disability. Although the syndrome is prevalent in 1:2500 individuals (Hagerman et al., 2009), school psychologists will be familiar with many symptoms of FXS, which include:
social avoidance and withdrawal
emotional and physiological reactivity
The presentation of these symptoms varies across children, with males generally demonstrating more severe symptoms than females due to random X inactivation. Differential diagnosis of FXS is particularly important in light of overlap among FXS symptoms with symptoms of several well-known disorders including autism, anxiety, and AD/HD. Over 85% of males with FXS experience comorbid psychopathology beyond developmental delay, and parents most commonly report a staggering four co-morbid conditions in males with FXS (Bailey, Raspa, Olmsted, & Holiday, 2008). This presents a challenge for school psychologists making eligibility decisions, such as deciding which IDEIA category best serves the child which becomes complex and based on many factors. Despite the commonality of comorbid psychopathology in FXS, diagnosing comorbid conditions in children with FXS and other intellectual disabilities presents several challenges to school-based practitioners:
Diagnosing psychopathology often integrates verbalized experiences and insight of the client, which may be difficult to attain in individuals with intellectual disabilities (Cordeiro, et al., 2011).
Symptoms may be presented differently across children with various communication abilities. For example, a child with modest verbal skills may present increased aggression due to frustration that stems from barriers in communicating his or her needs. Thus, the child’s aggression may stem from communication challenges versus oppositional or violent intentions.
Symptoms of many childhood disabilities often present substantial overlap, leaving school psychologists with difficult decisions related to teasing apart whether symptom clusters represent distinct disorders.
Once unique disorders are identified, the school psychologist must then determine whether separate diagnoses warrant unique types of treatments and which classification, if any, best serves the child.
These barriers, when not properly addressed, may delay or preclude appropriate services and treatments for children with disabilities. In light of the high prevalence of comorbid conditions associated with FXS and the challenges associated with diagnosing psychiatric conditions in children with intellectual disabilities, FXS presents a unique and valuable case for implementing best practices in differential diagnosis and eligibility decision making.
Autism Within FXS
Autism spectrum disorders are one of the most common and devastating comorbid conditions associated with FXS, with 90% of children with FXS demonstrating autism symptoms and 25- 60 percent meeting full diagnostic criteria (Bailey, Skinner, Davis, Whitmarsh, & Powell, 2008; Kaufmann et al., 2004; Rogers, Wehner, & Hagerman, 2001). Autism is a NDD associated with sociocommunicative deficits and restrictive or repetitive behaviors (American Psychiatric Association, 2004). Compared to children with FXS alone, children who present with both FXS and autism face higher risk for multiple negative outcomes, including:
receptive language delays (Rogers, et al., 2001)
increased behavior problems (Hatton et al., 2002)
increased withdrawal (Kaufmann, et al., 2004; Roberts, et al., 2007)
lower adaptive behavior skills (Hatton et al., 2003; Kau, et al., 2004; Rogers, et al., 2001)
social indifference (Budimirovic et al., 2006)
increasingly impaired cognitive profiles (Bailey et al., 2001).
Adequately assessing the presence of autism within FXS is essential due to the poorer prognosis associated with autism, as well as the subtle phenotypic differences that may substantially influence treatment decisions. School psychologists who understand the risk factors associated with autism in FXS may assist school personnel in implementing preventative curricular and behavioral goals aimed to minimize negative outcomes associated with the comorbid autism diagnosis, especially for those children who may not fall within the IDEIA definition of autism.
Notably, ruling out autism in FXS may also promote more appropriate service delivery and eligibility decisions for children with FXS. Consider the following research study:
These findings have direct relevance to school-based personnel working with students with FXS, as the results indicate that children with FXS who exhibit few autistic behaviors may initially appear shy and present like a child with a diagnosis of autism, but substantially “warm up” over time which is inconsistent with an autism diagnosis. This has implications for school psychologists and provides impetus for why school psychologists should take a differential diagnostic approach. First, autism should be specifically tested for in all cases of FXS. Second, a misdiagnosis or mis-labeling can be prevented when school psychologists are informed that autism symptoms are different in FXS. By considering these and other differential behavioral patterns, school psychologists may help teachers and other school professionals establish reasonable and targeted goals for students with NDDs while accounting for phenotypic variability associated with comorbid conditions. School personnel can learn to look beyond the IDEIA label and focus on the child.
Internalizing and Externalizing Disorders in FXS
Beyond autism, FXS is associated with a multitude of symptoms including intellectual disability, deficits in social interactions, increased levels of arousal, difficulties with attention, anxiety, impulsiveness, aggression, hyperactivity, impairments in communication, and gaze aversion. Based on these behaviors, a child with FXS may potentially meet IDEIA criteria as a child with an Intellectual Disability, Autism, Other Health Impairment, Learning Disability, or Emotional Disability. Given the range and severity of the core FXS symptoms, it is no surprise that individuals with this disorder meet DSM-IV-TR diagnostic criteria for high rates of psychiatric disorders, particularly anxiety and AD/HD.
As previously stated, anxiety is a primary symptom associated with FXS. Research on the prevalence of anxiety in this population suggests that as many as 86% of males and 77% of females meet diagnostic criteria for an anxiety disorder (Cordeiro et al., 2010). These rates are more than double the prevalence of anxiety disorders in individuals with intellectual disability, which have been suggested to be between 21-39% (Prasad et al., 2008; Dekker & Koot, 2003). This is important for school psychologists to be aware of to directly assess the potential for comorbid anxiety disorders as part of a comprehensive differential diagnostic assessment. The presence of anxiety disorders may directly affect treatment approaches within the school setting.
In addition to anxiety, core features of AD/HD are also common in FXS including inattention, impulsiveness, hyperactivity, and hyperarousal. Literature on AD/ HD in FXS suggests that as many as 90% of boys with the disorder also meet diagnostic criteria for AD/HD (Hagerman & Hagerman, 2002). This percentage, however, is lower for females for whom the prevalence rate has been suggested to be between 35-47% (Hagerman & Hagerman, 2002). Already at high risk for deficits in social interactions, the prevalence of AD/HD in FXS significantly impairs individuals’ social relationships, work and school performance, daily functioning, and quality of life. Medication has been found to be an efficacious form of treatment for AD/HD in individuals with an intellectual disability; and, results in FXS have been inconsistent (Roberts et al., 2011). As with anxiety disorders, understanding the underlying causes of particular behaviors in individuals should directly inform treatment. Understanding whether a child with FXS is acting out because of underlying anxiety or comorbid AD/HD is critical, and each child will differ.
Given the overlap of symptoms among disorders as defined in the DSM-IV-TR and the multiple IDEIA classifications these children may fall into, school psychologists will benefit from approaching comprehensive assessments from a differential diagnosis framework. Beyond the case of FXS and related disorders, differential diagnosis in the schools is critical for all NDDs. Treatment may differ for individuals depending on symptoms experienced and comorbid diagnoses, thus early differentiation is critical to provide prognostic information and guide treatment efforts. Additionally, early and accurate identification reduces lifelong costs associated with treatment by up to 65%. Because of school psychologists’ unique position as “diagnosticians and first responders” providing this information early is imperative. There is also an improvement in family well-being as early access to community resources is permitted. These resources are particularly important given that parents of children with NDDs express elevated stress and depression and, perhaps, a mild degree of learning or social problems themselves. Early understanding of NDDs and comorbid conditions may also assist with family planning efforts, as by definition these conditions are highly genetic.
In regard to treatment, school psychologists should remember that there is heterogeneity of all disorders, not just NDDs. An increased emphasis on the treatment of symptoms, instead of a one-size-fits-all approach to treatment planning, is important. School psychologists have an advantage of being able to decode this information and share with parents and teachers. Taking into account the literature on comorbid conditions, and studying best practices in differential assessment will have tremendous benefits not only for us as school psychologists, but for the children, families, and schools we serve.
American Psychiatric Association (2000).Diagnostic and statistical manual of mental disorders (4th ed., text revised). Washington, DC : American Psychiatric Association.
Andrews, G., Pine, D.S., Hobbs, M.J., Anderson, T.M., and Sunderland, M. (2009). Neurodevelopmental disorders: Cluster 2 of the proposed meta-structure for DSM -V and ICD -11. Psychological Medicine, 39, 2013-2023.
Bailey, D.B., Jr., Hatton, D.D., Tassone, F., Skinner, M., & Taylor, A.K. (2001b).Variability in FMRP and early development in males with FXS. American Journal on Mental Retardation, 1, 16-27.
Bailey, D.B., Jr., Skinner, D., Whitmarsh, I., Davis, A., & Powell, C. (2008). Ethical, legal, and social concerns about expanded newborn screening: Fragile X syndrome as a prototype for emerging issues. Pediatrics, 2008, 121, e693-e704.
Budimirovic DB, Bukelis I, Cox C, Gray RM , Tierney E, Kaufmann WE. (2006). Autism spectrum disorder infragile X syndrome: Differential contribution of adaptive socialization and social withdrawal. American Journal of Medical Genetics Part A, 140A, 1814–1826.
Cordeiro, L., Ballinger, E., Hagerman, R., &Hessl, D. (2010). Clinical assessment of DSM -IV anxiety disorders in fragile X syndrome: Prevalence and characterization. Journal of Neurodevelopmental Disorders, 6(1).
Crawford, D.C., Acuna, J.M., Sherman, S.L. (2001). FMR 1 and the fragile X syndrome: Human genome epidemiology review. Genetics in Medicine, 3, 359-371.
Crawford, D. C., Meadows, K. L., Newman, J. L., Taft, L. F., Scott, E., Leslie, M., . . . Sherman, S. L. (2002). Prevalence of the fragile X syndrome in African- Americans. Am J Med Genet, 110(3), 226-233. doi: 10.1002/ajmg.10427
Dawson, G. (2008). Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder. Developmental Psychopathology, 20(3), 775- 803.
Dekker, M.C., & Koot, H.M. (2003). DSM -IV disorders in children with borderline to moderate intellectual disability: Prevalence and impact. Journal of American Academy of Child and Adolescent Psychiatry, 42(8), 915-922.
Hagerman, R. (2002). The physical and behavioral phenotype.In R.J. Hagerman & P.J. Hagerman (Eds.), Fragile X syndrome: Diagnosis, treatment, and research(3rd ed., pp. 1-109). Baltimore, MD : Johns Hopkins University Press.
Hagerman, R.J., Berry-Kravis, E., Kaufmann, W.E., Ono, M.Y., Tartaglia, N., Lachiewicz, A., et al. (2009).Advances in the treatment of FXS. Pediatrics, 123(1), 378-390.
Hatton, D.D., Hooper, S.R., Bailey, D.B., Jr., Skinner, J.L., Sullivan, K.M., & Wheller, A. (2002).Problem behavior in boys with FXS. American Journal of Medical Genetics, 108, 105-116.
Hatton, D.D., Wheeler, A.C., Skinner, M.L., Bailey, D.B., Jr., Sullivan, K.M., Roberts, J.E., et al. (2003). Adaptive behavior in children with FXS. American Journal on Mental Retardation, 108(6), 373-390.
Kau, A.S., Tierney, E., Bukelis, I., Stump, M., Kates, W., Trescher, W., et al. (2004). Social behavior profile in young males with FXS: Characteristics and specificity. American Journal of Medical Genetics, 126, 9-17.
Kaufmann, W.E., Cortell, R., Kau, A., Bukelis, I., Tierney, E., Gray, R., et al. (2004). Autism spectrum disorder in FXS: Communication, social interaction, and specific behaviors. American Journal of Medical Genetics Part A, 129A, 225-234.
Meisels, S. J., & Atkins-Burnett, S. (2000). The elements of early childhood assessment. In J. P. Shonkoff & S. J.
Meisels (Eds.), Handbook of early childhood intervention (2nd ed.) (pp. 231- 257). New York: Cambridge University Press.
Prasad, S.E., Howley, S., Murphy, K.C. (2008). Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome. Developmental Disability Research Review, 14(1).26-34.
Reynolds, C., & Goldstein, S. (1999). Handbook of neurodevelopmental and genetic disorders in children. New York: The Guilford Press, pp. 3-8.
Roberts, J.E., Miranda, M., Boccia, M., Janes, H., Tonnsen, B., & Hatton, D. (2011). Treatment effects of stimulant medication in young boys with fragile X syndrome. Journal of Neurodevelopmental Disorders.
Roberts, J.E., Weisenfeld, L.A., Hatton, D.D., Heath, M., & Kaufmann, W.E. (2007).Social approach and autistic behavior in children with FXS. Journal of Autism and Developmental Disorders, 37(9), 1748-1760.
Rogers, S., Wehner, E., & Hagerman, R. (2001). The behavioral phenotype in fragile X: Symptoms of autism in very young children with FXS, idiopathic autism, and other developmental disorders. Journal of Developmental and Behavioral Pediatrics, 22, 409-417.
Rutter, M., Kim-Cohen, J., and Maughan, B. (2006).Continuities and discontinuities in psychopathology between childhood and adult life. Journal of Child Psychology and Psychiatry 47:3/4, 276–295.
Schwarte, A. (2008). Fragile X syndrome. School Psychology Quarterly, 23, 290-300 Roberts and colleagues (2007) studied the social approach behaviors of children with FXS and high or low levels of autistic symptoms. Results indicated the presence of autistic symptoms in children with FXS related to changes in social behaviors over time. As children with FXS and few autistic symptoms spent more time with unfamiliar examiners, their eye contact and social approach behaviors increased. However, children with FXS and high autistic symptoms did not show this pattern of improvement, instead maintaining high levels of social avoidance throughout sessions.