TY - JOUR
T1 - Heritable Connective Tissue Disorders in Childhood: Increased Fatigue, Pain, Disability and Decreased General Health
T2 - Increased Fatigue, Pain, Disability and Decreased General Health
AU - Warnink-Kavelaars, Jessica
AU - de Koning, Lisanne E.
AU - Rombaut, Lies
AU - Alsem, Mattijs W.
AU - Menke, Leonie A.
AU - Oosterlaan, Jaap
AU - Buizer, Annemieke I.
AU - Engelbert, Raoul H. H.
AU - On Behalf Of The Pediatric Heritable Connective Tissue Disorders Study Group, null
N1 - Funding Information: SIA RAAK-PRO, part of the Dutch Organization for Scientific Research (NWO; SVB.RAAK> PRO02.007), is a four-year research grant allocated to the project ?Follow You?a follow up programme on physical, psychosocial functioning and participation in children and adolescents with (heritable) connective tissue disorders?. The funder/sponsor did not participate in the work. Acknowledgments: We thank the parents, children and adolescents who participated in this study. We also wish to acknowledge the Dutch Network Marfan syndrome and related connective tissue disorders, the European Reference Network (ERN) Skin-Mendelian connective tissue disorders and both the Marfan and Ehlers-Danlos patient associations for the productive discussions. We thank Kobie Verhoogt for her work during her medical research internship and the Clinical Research Unit Amsterdam UMC for their statistical advice. We are grateful to SIA RAAK-PRO, part of the Dutch Organization for Scientific Research (NWO; SVB.RAAK>PRO02.007), for funding this project, which is part of a four-year research grant allocated to the project ?Follow You-a follow-up programme on physical, psychosocial functioning and participation in children and adolescents with (heritable) connective tissue disorders?. Funding Information: Funding: SIA RAAK-PRO, part of the Dutch Organization for Scientific Research (NWO; SVB.RAAK> PRO02.007), is a four-year research grant allocated to the project “Follow You–a follow up programme on physical, psychosocial functioning and participation in children and adolescents with (heritable) connective tissue disorders”. The funder/sponsor did not participate in the work. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Heritable Connective Tissue Disorders (HCTD) show an overlap in the physical features that can evolve in childhood. It is unclear to what extent children with HCTD experience burden of disease. This study aims to quantify fatigue, pain, disability and general health with standardized validated questionnaires. METHODS: This observational, multicenter study included 107 children, aged 4-18 years, with Marfan syndrome (MFS), 58%; Loeys-Dietz syndrome (LDS), 7%; Ehlers-Danlos syndromes (EDS), 8%; and hypermobile Ehlers-Danlos syndrome (hEDS), 27%. The assessments included PROMIS Fatigue Parent-Proxy and Pediatric self-report, pain and general health Visual-Analogue-Scales (VAS) and a Childhood Health Assessment Questionnaire (CHAQ). RESULTS: Compared to normative data, the total HCTD-group showed significantly higher parent-rated fatigue T-scores (M = 53 (SD = 12), p = 0.004, d = 0.3), pain VAS scores (M = 2.8 (SD = 3.1), p < 0.001, d = 1.27), general health VAS scores (M = 2.5 (SD = 1.8), p < 0.001, d = 2.04) and CHAQ disability index scores (M = 0.9 (SD = 0.7), p < 0.001, d = 1.23). HCTD-subgroups showed similar results. The most adverse sequels were reported in children with hEDS, whereas the least were reported in those with MFS. Disability showed significant relationships with fatigue (p < 0.001, rs = 0.68), pain (p < 0.001, rs = 0.64) and general health (p < 0.001, rs = 0.59). CONCLUSIONS: Compared to normative data, children and adolescents with HCTD reported increased fatigue, pain, disability and decreased general health, with most differences translating into very large-sized effects. This new knowledge calls for systematic monitoring with standardized validated questionnaires, physical assessments and tailored interventions in clinical care.
AB - Heritable Connective Tissue Disorders (HCTD) show an overlap in the physical features that can evolve in childhood. It is unclear to what extent children with HCTD experience burden of disease. This study aims to quantify fatigue, pain, disability and general health with standardized validated questionnaires. METHODS: This observational, multicenter study included 107 children, aged 4-18 years, with Marfan syndrome (MFS), 58%; Loeys-Dietz syndrome (LDS), 7%; Ehlers-Danlos syndromes (EDS), 8%; and hypermobile Ehlers-Danlos syndrome (hEDS), 27%. The assessments included PROMIS Fatigue Parent-Proxy and Pediatric self-report, pain and general health Visual-Analogue-Scales (VAS) and a Childhood Health Assessment Questionnaire (CHAQ). RESULTS: Compared to normative data, the total HCTD-group showed significantly higher parent-rated fatigue T-scores (M = 53 (SD = 12), p = 0.004, d = 0.3), pain VAS scores (M = 2.8 (SD = 3.1), p < 0.001, d = 1.27), general health VAS scores (M = 2.5 (SD = 1.8), p < 0.001, d = 2.04) and CHAQ disability index scores (M = 0.9 (SD = 0.7), p < 0.001, d = 1.23). HCTD-subgroups showed similar results. The most adverse sequels were reported in children with hEDS, whereas the least were reported in those with MFS. Disability showed significant relationships with fatigue (p < 0.001, rs = 0.68), pain (p < 0.001, rs = 0.64) and general health (p < 0.001, rs = 0.59). CONCLUSIONS: Compared to normative data, children and adolescents with HCTD reported increased fatigue, pain, disability and decreased general health, with most differences translating into very large-sized effects. This new knowledge calls for systematic monitoring with standardized validated questionnaires, physical assessments and tailored interventions in clinical care.
KW - Children
KW - Disability
KW - Ehlers-Danlos syndromes
KW - Fatigue
KW - General health
KW - Heritable Connective Tissue Disorders
KW - Hyper-mobile Ehlers-Danlos syndrome
KW - Loeys-Dietz syndrome
KW - Marfan syndrome
KW - Pain
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85107451758&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34071423
UR - http://www.scopus.com/inward/record.url?scp=85107451758&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/genes12060831
DO - https://doi.org/10.3390/genes12060831
M3 - Article
C2 - 34071423
SN - 2073-4425
VL - 12
JO - Genes
JF - Genes
IS - 6
M1 - 831
ER -