. 2021 May 28;12(6):831.

doi: 10.3390/genes12060831.

Heritable Connective Tissue Disorders in Childhood: Increased Fatigue, Pain, Disability and Decreased General Health

Jessica Warnink-Kavelaars¹, Lisanne E de Koning², Lies Rombaut³, Mattijs W Alsem¹, Leonie A Menke⁴, Jaap Oosterlaan⁵, Annemieke I Buizer^{1

4

6}, Raoul H H Engelbert^{1

2

4}, On Behalf Of The Pediatric Heritable Connective Tissue Disorders Study Group^{1

2

3

4

5

6

7

8

9

10

11

12

13}

Affiliations

¹ Department of Rehabilitation Medicine, Amsterdam Movement Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
² Center of Expertise Urban Vitality, Faculty of Health, Amsterdam University of Applied Sciences, Tafelbergweg 51, 1105 BD Amsterdam, The Netherlands.
³ Center of Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
⁴ Department of Pediatrics, Emma Children's Hospital, University of Amsterdam, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁵ Emma Neuroscience Group, Amsterdam Reproduction & Development, Department of Pediatrics, Emma Children's Hospital, University of Amsterdam, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁶ Department of Rehabilitation Medicine, Rehabilitation and Development, Amsterdam Movement Sciences Institute, Amsterdam UMC, Vrije University of Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
⁷ Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁸ Department of Genetics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
⁹ Center for Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
¹⁰ Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
¹¹ Department of Clinical Genetics, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
¹² Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium.
¹³ Department of Physical and Rehabilitation Medicine, Child Rehabilitation, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.

PMID: 34071423
PMCID: PMC8229209
DOI: 10.3390/genes12060831

Heritable Connective Tissue Disorders in Childhood: Increased Fatigue, Pain, Disability and Decreased General Health

Jessica Warnink-Kavelaars et al. Genes (Basel). 2021.

. 2021 May 28;12(6):831.

doi: 10.3390/genes12060831.

Authors

Affiliations

¹ Department of Rehabilitation Medicine, Amsterdam Movement Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
² Center of Expertise Urban Vitality, Faculty of Health, Amsterdam University of Applied Sciences, Tafelbergweg 51, 1105 BD Amsterdam, The Netherlands.
³ Center of Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
⁴ Department of Pediatrics, Emma Children's Hospital, University of Amsterdam, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁵ Emma Neuroscience Group, Amsterdam Reproduction & Development, Department of Pediatrics, Emma Children's Hospital, University of Amsterdam, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁶ Department of Rehabilitation Medicine, Rehabilitation and Development, Amsterdam Movement Sciences Institute, Amsterdam UMC, Vrije University of Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
⁷ Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁸ Department of Genetics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
⁹ Center for Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
¹⁰ Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
¹¹ Department of Clinical Genetics, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
¹² Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium.
¹³ Department of Physical and Rehabilitation Medicine, Child Rehabilitation, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.

PMID: 34071423
PMCID: PMC8229209
DOI: 10.3390/genes12060831

Abstract

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, r_s = 0.68), pain (p < 0.001, r_s = 0.64) and general health (p < 0.001, r_s = 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.

Keywords: Ehlers-Danlos syndromes; Heritable Connective Tissue Disorders; Loeys-Dietz syndrome; Marfan syndrome; children; disability; fatigue; general health; hypermobile Ehlers-Danlos syndrome; pain.

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Conflict of interest statement

The authors declare no conflict of interest.

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Heritable Connective Tissue Disorders in Childhood: Increased Fatigue, Pain, Disability and Decreased General Health

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Heritable Connective Tissue Disorders in Childhood: Increased Fatigue, Pain, Disability and Decreased General Health

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