The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism
The Ehlers–Danlos syndromes are a group of multisystemic heritable connective tissue disorders with clinical presentations that range from multiple congenital malformations, over adolescent-onset debilitating or even life-threatening complications of connective tissue fragility, to mild conditions t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/2/265 |
| _version_ | 1797479937832124416 |
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| author | Tim Van Damme Marlies Colman Delfien Syx Fransiska Malfait |
| author_facet | Tim Van Damme Marlies Colman Delfien Syx Fransiska Malfait |
| author_sort | Tim Van Damme |
| collection | DOAJ |
| description | The Ehlers–Danlos syndromes are a group of multisystemic heritable connective tissue disorders with clinical presentations that range from multiple congenital malformations, over adolescent-onset debilitating or even life-threatening complications of connective tissue fragility, to mild conditions that remain undiagnosed in adulthood. To date, thirteen different EDS types have been recognized, stemming from genetic defects in 20 different genes. While initial biochemical and molecular analyses mainly discovered defects in genes coding for the fibrillar collagens type I, III and V or their modifying enzymes, recent discoveries have linked EDS to defects in non-collagenous matrix glycoproteins, in proteoglycan biosynthesis and in the complement pathway. This genetic heterogeneity explains the important clinical heterogeneity among and within the different EDS types. Generalized joint hypermobility and skin hyperextensibility with cutaneous fragility, atrophic scarring and easy bruising are defining manifestations of EDS; however, other signs and symptoms of connective tissue fragility, such as complications of vascular and internal organ fragility, orocraniofacial abnormalities, neuromuscular involvement and ophthalmological complications are variably present in the different types of EDS. These features may help to differentiate between the different EDS types but also evoke a wide differential diagnosis, including different inborn errors of metabolism. In this narrative review, we will discuss the clinical presentation of EDS within the context of inborn errors of metabolism, give a brief overview of their underlying genetic defects and pathophysiological mechanisms and provide a guide for the diagnostic approach. |
| first_indexed | 2024-03-09T21:52:57Z |
| format | Article |
| id | doaj.art-927cbd823a284e01a996b1baf35f3546 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T21:52:57Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-927cbd823a284e01a996b1baf35f35462023-11-23T20:04:11ZengMDPI AGGenes2073-44252022-01-0113226510.3390/genes13020265The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of MetabolismTim Van Damme0Marlies Colman1Delfien Syx2Fransiska Malfait3Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, 9000 Ghent, BelgiumCenter for Medical Genetics, Department of Biomolecular Medicine, Ghent University, 9000 Ghent, BelgiumCenter for Medical Genetics, Department of Biomolecular Medicine, Ghent University, 9000 Ghent, BelgiumCenter for Medical Genetics, Department of Biomolecular Medicine, Ghent University, 9000 Ghent, BelgiumThe Ehlers–Danlos syndromes are a group of multisystemic heritable connective tissue disorders with clinical presentations that range from multiple congenital malformations, over adolescent-onset debilitating or even life-threatening complications of connective tissue fragility, to mild conditions that remain undiagnosed in adulthood. To date, thirteen different EDS types have been recognized, stemming from genetic defects in 20 different genes. While initial biochemical and molecular analyses mainly discovered defects in genes coding for the fibrillar collagens type I, III and V or their modifying enzymes, recent discoveries have linked EDS to defects in non-collagenous matrix glycoproteins, in proteoglycan biosynthesis and in the complement pathway. This genetic heterogeneity explains the important clinical heterogeneity among and within the different EDS types. Generalized joint hypermobility and skin hyperextensibility with cutaneous fragility, atrophic scarring and easy bruising are defining manifestations of EDS; however, other signs and symptoms of connective tissue fragility, such as complications of vascular and internal organ fragility, orocraniofacial abnormalities, neuromuscular involvement and ophthalmological complications are variably present in the different types of EDS. These features may help to differentiate between the different EDS types but also evoke a wide differential diagnosis, including different inborn errors of metabolism. In this narrative review, we will discuss the clinical presentation of EDS within the context of inborn errors of metabolism, give a brief overview of their underlying genetic defects and pathophysiological mechanisms and provide a guide for the diagnostic approach.https://www.mdpi.com/2073-4425/13/2/265Ehlers–Danlos syndromesgeneticspathophysiologyinborn errors of metabolism |
| spellingShingle | Tim Van Damme Marlies Colman Delfien Syx Fransiska Malfait The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism Genes Ehlers–Danlos syndromes genetics pathophysiology inborn errors of metabolism |
| title | The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism |
| title_full | The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism |
| title_fullStr | The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism |
| title_full_unstemmed | The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism |
| title_short | The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism |
| title_sort | ehlers danlos syndromes against the backdrop of inborn errors of metabolism |
| topic | Ehlers–Danlos syndromes genetics pathophysiology inborn errors of metabolism |
| url | https://www.mdpi.com/2073-4425/13/2/265 |
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