To the Editor:

The recently published practice parameter concerning the evaluation of the child with global developmental delay (GDD) is flawed by the authors’ decision to reinterpret this perfectly clear term, which has always been understood to encompass cognitive delay, in such a fashion that a child with delays in only two of five domains would be thus classified.1 Thus a child with cerebral palsy and consequent impairment in motor and activities of daily living skills, but without cognitive, social, or language impairment, would meet the authors’ definition. This stands in contradiction to the literature that they cite (authors’ references 3–7) in support of their definition. It further contradicts the authors’ statement elsewhere that global delay is to be distinguished from autistic spectrum disorder: on the basis of their definition, such a distinction would not be possible. It is also troubling to see an unmodified recommendation for routine MRI studies in the abstract: this was appropriately modified in the text. As presented, this parameter would appear to have been approved by the Practice Committee of the Child Neurology Society (CNS) as well as the American Academy of Neurology (AAN) Quality Standards Subcommittee (QSS). As a member of the CNS Practice Committee, I would like to raise some procedural concerns. When polled at the last of the two Practice Committee meetings where this parameter was (briefly) presented, only one member expressed approval of the definition. However, abstaining votes from absent members were counted as approving (abstention from commentary has usually meant failure to read, an acknowledged problem in this committee) and request for simultaneous publication of a dissenting opinion was denied by the Co-Chair of the QSS, who …

Practice parameter: Evaluation of the child with global developmental delay: Report of the Quality

Evidence report: genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

Purpose of review The study summarizes supportive epidemiological data regarding the true co-occurrence (comorbidity) and course of mental disorders in children with intellectual disability/intellectual developmental disorders (ID/IDD) across the lifespan. Recent findings Published studies involving representative populations of children and adolescents with ID/IDD have demonstrated a three to four-fold increase in prevalence of co-occurring mental disorders. The effect of age, sex, and severity (mild, moderate, severe, and profound) and socioeconomic status on prevalence is currently not clearly understood. To date there are no prevalence estimates of co-occurring mental disorders in youth identified using the new DSM-5 (and proposed ICD-11) definition of ID/IDD using measures of intellectual functions and deficits in adaptive functioning with various severity levels defined on the basis of adaptive functioning, and not intellectual quotient scores. Summary The true relationship between two forms of morbidity remains complex and causal relationships that may be true for one disorder may not apply to another. The new conceptualization of ID/IDD offers a developmentally better informed psychobiological approach that can help distinguish co-occurrence of mental disorders within the neurodevelopmental section with onset during the developmental period as well as the later onset of other mental disorders.

The Co-Occurrence of Other Mental Disorders in Children and Adolescents With Intellectual Disability/Intellectual Developmental Disorder

The widespread availability of genetic testing for those with neurodevelopmental disorders has highlighted the importance of many genes necessary for the proper development and function of the nervous system. One gene found to be genetically altered in the X-linked intellectual disability disorder Claes-Jensen syndrome is KDM5C, which encodes a histone demethylase that regulates transcription by altering chromatin. While the genetic link between KDM5C and cognitive (dys)function is clear, how KDM5C functions to control transcriptional programs within neurons to impact their growth and activity remains the subject of ongoing research. Here, we review our current knowledge of Claes-Jensen syndrome and discuss important new data using model organisms that have revealed the importance of KDM5C in regulating aspects of neuronal development and function. Continued research into the molecular and cellular activities regulated by KDM5C is expected to provide critical etiological insights into Claes-Jensen syndrome and highlight potential targets for developing therapies to improve the quality of life of those affected.

Molecular and cellular events linking variants in the histone demethylase KDM5C to the intellectual disability disorder Claes-Jensen syndrome

Background Previous studies have mostly explored the comorbidities of Global developmental delay (GDD) in children with Autism Spectrum Disorders (ASD) from the perspective of ASD. The study focus on the perspective of GDD to investigate the prevalence and developmental profiles of ASD in GDD and to explore the correlation between the developmental level and symptoms of autism. Methods Clinical data of 521 children with GDD aged from 24 to 60 months were retrospectively analyzed. Analyses were performed first for the whole sample and then subdivided into two subgroups (GDD+ASD−, GDD+ASD+) according to whether had ASD. Symptoms of autism were evaluated by the Autism Behavior Checklist and the Childhood Autism Rating Scale. The Chinese version of the Gesell Developmental Schedules was used to evaluate the level of children's mental development. Result The prevalence of ASD in children with GDD was 62.3%. The total average developmental quotient (DQ) of GDD was mildly deficient and was negatively correlated with symptoms of autism (p < 0.05); language ability was severe and extremely severe deficient (P < 0.05). GDD+ASD− group and GDD+ASD+ group have some common points as well as differences in the developmental features. The language delay of children in both subgroups was the most obviously defected, thereafter followed by the item of personal social activity. In the GDD+ASD+ group, the DQ of gross motor skills>fine motor skills>adaptability (p < 0.05). There were no significant differences among the DQ of gross motor skills, fine motor skills and adaptability in GDD+ASD− group (p > 0.05). The GDD+ASD−group had better adaptability, fine motor skills, language ability, personal social activity than that of the GDD+ASD+ group, but the gross motor skills in GDD+ASD− group were worse (p < 0.05). Conclusion GDD children have a high proportion of comorbid ASD, and GDD children with poorer developmental levels are more likely to have ASD symptoms. Development profiles in both GDD+ASD− children and GDD+ASD+ children have common features but there are also differences. GDD+ASD+ group is worse than GDD+ASD− group in terms of the overall development level.

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Prevalence and Developmental Profiles of Autism Spectrum Disorders in Children With Global Developmental Delay

Between 1% and 3% of persons in general population are estimated to have some degree of intellectual disability. A diagnosis of intellectual disability is based on clinical history, level of intellectual ability and level of adaptive function. Both, the intellectual and adaptive functioning are measured using individually administered standardized tests. More than 75% of persons who have intellectual disability have mild intellectual disability and an underlying specific etiology is less likely to be identified; whereas, in a small percentage of persons with severe intellectual disability, an underlying specific biologic cause is highly likely to be identified. Genetic abnormalities, inborn errors of metabolism and brain malformations are major categories of causes identified in severe to profound intellectual disability. The initial clinical presentation and recognition depends on the severity and underlying cause of intellectual disability. The etiology, severity, cognitive abilities, and adaptive function, vary among persons with intellectual disability and need consideration in developing a treatment plan. The physician plays an essential role in the evaluation, treatment of associated medical conditions and preventive care, and in facilitating and coordinating consultative services and community based care.

Arlene Ho

Papers

A clinical primer on intellectual disability