FROM THE AMERICAN ACADEMY OF PEDIATRICS Guidance for the Clinician in Rendering Pediatric Care CLINICAL REPORT Comprehensive Evaluation of the Child With Intellectual Disability or Global Developmental Delays John B. Moeschler, MD, MS, FAAP, FACMG, Michael Shevell, MDCM, FRCP, and COMMITTEE ON GENETICS abstract ABBREVIATIONS Global developmental delay and intellectual disability are relatively — AAP American Academy of Pediatrics common pediatric conditions. This report describes the recommended CMA—chromosome microarray CNS—central nervous system clinical genetics diagnostic approach. The report is based on a review CNV—copy number variant of published reports, most consisting of medium to large case series of CT—computed tomography diagnostic tests used, and the proportion of those that led to a diag- FISH—fluorescent in situ hybridization GAA—guanidinoacetate nosis in such patients. Chromosome microarray is designated as GDD—global developmental delay a first-line test and replaces the standard karyotype and fluorescent ID—intellectual disability in situ hybridization subtelomere tests for the child with intellectual — XLID X-linked intellectual disability disability of unknown etiology. Fragile X testing remains an important This document is copyrighted and is property of the American first-line test. The importance of considering testing for inborn errors Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American of metabolism in this population is supported by a recent systematic Academy of Pediatrics. Any conflicts have been resolved through review of the literature and several case series recently published. The a process approved by the Board of Directors. The American role of brain MRI remains important in certain patients. There is also Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of a discussion of the emerging literature on the use of whole-exome se- this publication. quencing as a diagnostic test in this population. Finally, the importance The guidance in this report does not indicate an exclusive of intentional comanagement among families, the medical home, course of treatment or serve as a standard of medical care. and the clinical genetics specialty clinic is discussed. Pediatrics Variations, taking into account individual circumstances, may be 2014;134:e903–e918 appropriate. The purpose of this clinical report of the American Academy of Pe- diatrics (AAP) is to describe an optimal medical genetics evaluation of the child with intellectual disability (ID) or global developmental delays (GDDs). The intention is to assist the medical home in preparing families properly for the medical genetics evaluation process. This report addresses the advances in diagnosis and treatment of children with intellectual disabilities since the publication of the original AAP www.pediatrics.org/cgi/doi/10.1542/peds.2014-1839 clinical report in 20061 and provides current guidance for the medical doi:10.1542/peds.2014-1839 genetics evaluation. One intention is to inform primary care providers All clinical reports from the American Academy of Pediatrics in the setting of the medical home so that they and families are automatically expire 5 years after publication unless reaffirmed, knowledgeable about the purpose and process of the genetics eval- revised, or retired at or before that time. uation. This report will emphasize advances in genetic diagnosis while PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). updating information regarding the appropriate evaluation for inborn Copyright © 2014 by the American Academy of Pediatrics errors of metabolism and the role of imaging in this context. The reader is referred to the 2006 clinical report for background in- formation that remains relevant, including the roles of the medical home or pediatric primary care provider. This clinical report will not address the importance of developmental screening in the medical home, nor will it address the diagnostic PEDIATRICS Volume 134, Number 3, September 2014 e903 Downloaded from www.aappublications.org/news by guest on September 26, 2021 evaluation of the child with an autism intellectual disabilities and their fami- have preferred to have an [etiologic] spectrum disorder who happens to lies.3–5 Although perhaps difficult to diagnosis, if given the option,” partic- have ID as a co-occurring disability. measure, this “healing touch” contrib- ularly early in the course of the (For AAP guidance related to Autism utes to the general well-being of the symptoms. Spectrum Disorders, see Johnson and family. “As physicians we have experi- As was true of the 2006 clinical report, Myers.2) ence with other children who have the this clinical report will not address the For both pediatric primary care pro- same disorder, access to management etiologic evaluation of young children viders and families, there are specific programs, knowledge of the prognosis, who are diagnosed with cerebral palsy, benefits to establishing an etiologic awareness of research on understanding autism, or a single-domain develop- diagnosis (Table 1): clarification of eti- the disease and many other elements mental delay (gross motor delay or ology; provision of prognosis or ex- that when shared with the parents will specific language impairment).1 Some pected clinical course; discussion of give them a feeling that some control children will present both with GDD genetic mechanism(s) and recurrence is possible.”5 and clinical features of autism. In risks; refined treatment options; the Makela et al6 studied, in depth, 20 such cases, the judgment of the clin- avoidance of unnecessary and re- families of children with ID with and ical geneticist will be important in dundant diagnostic tests; information without an etiologic diagnosis and determining the evaluation of the child regarding treatment, symptom man- found that these families had specific depending on the primary neuro- agement, or surveillance for known stated needs and feelings about what developmental diagnosis. It is recog- complications; provision of condition- a genetic diagnosis offers: nized that the determination that an fi speci c family support; access to re- 1. Validation: a diagnosis established infant or young child has a cognitive search treatment protocols; and the that the problem (ID) was credible, disability can be a matter of clinical opportunity for comanagement of pa- which empowered them to advo- judgment, and it is important for the tients, as appropriate, in the context of cate for their child. pediatrician and consulting clinical a medical home to ensure the best geneticist to discuss this before de- 2. Information: a diagnosis was felt to health, social, and health care services ciding on the best approach to the help guide expectations and man- satisfaction outcomes for the child and diagnostic evaluation.”1 agement immediately and provide family. The presence of an accurate hope for treatment or cure in fu- etiologic diagnosis along with a knowl- ture. INTELLECTUAL DISABILITY edgeable, experienced, expert clinician is one factor in improving the psycho- 3. Procuring services: the diagnosis ID is a developmental disability pre- social outcomes for children and with assisted families in obtaining desired senting in infancy or the early child- services, particularly in schools. hood years, although in some cases, it 4. Support: families expressed the need cannot be diagnosed until the child is TABLE 1 The Purposes of the for emotional companionship that a older than ∼5 years of age, when Comprehensive Medical Genetics fi “ standardized measures of develop- Evaluation of the Young Child With speci c diagnosis (or similar chal- GDD or ID lenges”) assisted in accessing. mental skills become more reliable and valid. The American Association 5. Need to know: families widely dif- 1. Clarification of etiology on Intellectual and Developmental 2. Provision of prognosis or expected clinical fered in their “need to know” aspe- Disability defines ID by using mea- course cific diagnosis, ranging from strong 3. Discussion of genetic mechanism(s) and sures of 3 domains: intelligence (IQ), to indifferent. recurrence risks adaptive behavior, and systems of 4. Refined treatment options 6. Prenatal testing: families varied in 7 5. Avoidance of unnecessary or redundant supports afforded the individual. diagnostic tests their emotions, thoughts, and actions Thus, one cannot rely solely on the 6. Information regarding treatment, symptom regarding prenatal genetic diagno- measure of IQ to define ID. More re- management, or surveillance for known sis. cently, the term ID has been suggested complications 6 7,8 7. Provision of condition-specific family support For some families in the Makela et al to replace “mental retardation.” For 8. Access to research treatment protocols study, the clinical diagnosis of autism, the purposes of this clinical report, 9. Opportunity for comanagement of appropriate for example, was sufficient and often the American Association on Intel- patients in the context of a medical home to “ fi ensure the best health, social, and health care more useful than a rare but speci c lectual and Developmental Disability services satisfaction outcomes for the child and etiological diagnosis.” These authors definition is used: “Intellectual dis- family report that “all of the families would ability is a disability characterized by e904 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded