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      Neuropsychiatric Disease and Treatment (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on all aspects of neuropsychiatric and neurological disorders. Sign up for email alerts here.

      63,741 Monthly downloads/views I 2.989 Impact Factor I 4.5 CiteScore I 1.09 Source Normalized Impact per Paper (SNIP) I 0.744 Scimago Journal & Country Rank (SJR)

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      Prevalence of ADHD and Autism Spectrum Disorder in Children with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome: A Retrospective Study

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          Abstract

          Introduction

          Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are both characterized by generalized hypermobility, in combination with pain, affected proprioception, and pronounced fatigue. Clinical observation indicates that behavioral problems, hyperactivity, and autistic traits are overrepresented in children with those conditions. The purpose of this retrospective study was to establish the prevalence of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) among children with HSD and hEDS treated in our clinic since 2012.

          Subjects and Methods

          Since Ehlers-Danlos syndrome (EDS) diagnostic criteria and international classification were changed in 2017, we equate the older diagnosis EDS hypermobility type with the newer hEDS and the older hypermobility syndrome with HSD. A registry search from the computerized medical record system found 201 children (88 boys, 113 girls) aged 6–18 years who were treated at our pediatrics department with the diagnoses HSD or EDS. All medical records (113 with HSD, 88 with EDS) were reviewed, and key symptoms such as fatigue and pain, as well as diagnosis of ADHD/ASD, were recorded.

          Results

          All EDS cases could be classified as hEDS. Of the entire study cohort, 16% had a verified ADHD diagnosis and a further 7% were undergoing ADHD diagnostic investigation. Significantly more children with hEDS had ADHD compared to children with HSD (p=0.02). In the age group 15–16 years, 35% of those with hEDS had ADHD and, among those aged 17–18 years, ADHD was present in 46%. Children with coexisting ADHD showed a significantly higher proportion of associated symptoms such as fatigue, sleep-problems, and urinary tract problems. ASD had been verified in 6% of the children. Of those with ASD, 92% had sleep problems.

          Conclusion

          This study shows a strong association between HSD or hEDS and ADHD or ASD. Therefore, children with HSD or hEDS may need to be routinely screened for neuropsychiatric symptoms.

          Most cited references30

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          The 2017 international classification of the Ehlers-Danlos syndromes.

          Fransiska Malfait, Clair A. Francomano, Peter K. Byers … (2017)
          The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen-encoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. © 2017 Wiley Periodicals, Inc.
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            Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK).

            P. Beighton, A. De Paepe, B. Steinmann … (1998)
            Categorization of the Ehlers-Danlos syndromes began in the late 1960s and was formalized in the Berlin nosology. Over time, it became apparent that the diagnostic criteria established and published in 1988 did not discriminate adequately between the different types of Ehlers-Danlos syndromes or between Ehlers-Danlos syndromes and other phenotypically related conditions. In addition, elucidation of the molecular basis of several Ehlers-Danlos syndromes has added a new dimension to the characterization of this group of disorders. We propose a revision of the classification of the Ehlers-Danlos syndromes based primarily on the cause of each type. Major and minor diagnostic criteria have been defined for each type and complemented whenever possible with laboratory findings. This simplified classification will facilitate an accurate diagnosis of the Ehlers-Danlos syndromes and contribute to the delineation of phenotypically related disorders.
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              A review of executive function deficits in autism spectrum disorder and attention-deficit/hyperactivity disorder

              Francesco Craig, Francesco Margari, Anna R Legrottaglie … (2016)
              Executive dysfunction has been shown to be a promising endophenotype in neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This article reviewed 26 studies that examined executive function comparing ASD and/or ADHD children. In light of findings from this review, the ASD + ADHD group appears to share impairment in both flexibility and planning with the ASD group, while it shares the response inhibition deficit with the ADHD group. Conversely, deficit in attention, working memory, preparatory processes, fluency, and concept formation does not appear to be distinctive in discriminating from ASD, ADHD, or ASD + ADHD group. On the basis of neurocognitive endophenotype, the common co-occurrence of executive function deficits seems to reflect an additive comorbidity, rather than a separate condition with distinct impairments.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Neuropsychiatr Dis Treat
                Journal ID (iso-abbrev): Neuropsychiatr Dis Treat
                Journal ID (publisher-id): ndt
                Journal ID (pmc): neurodist
                Title: Neuropsychiatric Disease and Treatment
                Publisher: Dove
                ISSN (Print): 1176-6328
                ISSN (Electronic): 1178-2021
                Publication date (Electronic): 10 February 2021
                Publication date Collection: 2021
                Volume: 17
                Pages: 379-388
                Affiliations
                [1 ]Department of Pediatrics, Skaraborg Hospital , Skövde, Sweden
                [2 ]Division of Pediatrics, Department of Biomedical and Clinical Sciences (BKV), Medical Faculty, Linköping University , Linköping, Sweden
                [3 ]Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg , Gothenburg, Sweden
                Author notes
                Correspondence: Erik Kindgren Department of Pediatrics, Skaraborg Hospital , Lövängsvägen, Skövde, 541 42, SwedenTel +46104739222Fax +46500478356 Email erik@kindgren.org
                Author information
                http://orcid.org/0000-0001-8023-1914
                http://orcid.org/0000-0003-1278-4554
                Article
                Publisher ID: 290494
                DOI: 10.2147/NDT.S290494
                PMC ID: 7882457
                PubMed ID: 33603376
                SO-VID: 4fee8ef8-f144-4564-87f9-90d61517c690
                Copyright © © 2021 Kindgren et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 07 November 2020
                Date accepted : 19 December 2020
                Page count
                Figures: 2, Tables: 3, References: 32, Pages: 10
                Funding
                Funded by: R&D Centre Skaraborg Hospital;
                This research was funded by Research & Development Centre, Skaraborg Hospital. The sponsor was not involved in any of the stages from study design to submission of the paper for publication.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Neurology
                Keywords: adhd,autism spectrum disorder,children,hypermobility spectrum disorder,ehlers-danlos syndrome
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: adhd, autism spectrum disorder, children, hypermobility spectrum disorder, ehlers-danlos syndrome

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