The Connective Tissue Disorder Associated with Recessive Variants in the SLC39A13 Zinc Transporter Gene (Spondylo-Dysplastic Ehlers-Danlos Syndrome Type 3): Insights from Four Novel Patients and Follow-Up on Two Original Cases.

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License: CC BY 4.0
Serval ID
serval:BIB_DA412F996FF0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Connective Tissue Disorder Associated with Recessive Variants in the SLC39A13 Zinc Transporter Gene (Spondylo-Dysplastic Ehlers-Danlos Syndrome Type 3): Insights from Four Novel Patients and Follow-Up on Two Original Cases.
Journal
Genes
Author(s)
Kumps C., Campos-Xavier B., Hilhorst-Hofstee Y., Marcelis C., Kraenzlin M., Fleischer N., Unger S., Superti-Furga A.
ISSN
2073-4425 (Electronic)
ISSN-L
2073-4425
Publication state
Published
Issued date
14/04/2020
Peer-reviewed
Oui
Volume
11
Number
4
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Recessive loss-of-function variants in SLC39A13, a putative zinc transporter gene, were first associated with a connective tissue disorder that is now called "Ehlers-Danlos syndrome, spondylodysplastic form type 3" (SCD-EDS, OMIM 612350) in 2008. Nine individuals have been described. We describe here four additional affected individuals from three consanguineous families and the follow up of two of the original cases. In our series, cardinal findings included thin and finely wrinkled skin of the hands and feet, characteristic facial features with downslanting palpebral fissures, mild hypertelorism, prominent eyes with a paucity of periorbital fat, blueish sclerae, microdontia, or oligodontia, and-in contrast to most types of Ehlers-Danlos syndrome-significant short stature of childhood onset. Mild radiographic changes were observed, among which platyspondyly is a useful diagnostic feature. Two of our patients developed severe keratoconus, and two suffered from cerebrovascular accidents in their twenties, suggesting that there may be a vascular component to this condition. All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates, pyridinoline-to-deoxypyridinoline, in urine, suggesting that this simple test is diagnostically useful. Additionally, analysis of the facial features of affected individuals by DeepGestalt technology confirmed their specificity and may be sufficient to suggest the diagnosis directly. Given that the clinical presentation in childhood consists mainly of short stature and characteristic facial features, the differential diagnosis is not necessarily that of a connective tissue disorder and therefore, we propose that SLC39A13 is included in gene panels designed to address dysmorphism and short stature. This approach may result in more efficient diagnosis.
Keywords
DeepGestalt technology, Ehlers–Danlos syndrome, SLC39A13, connective tissue, dysmorphology, short stature
Pubmed
Open Access
Yes
Create date
25/04/2020 19:15
Last modification date
15/01/2021 7:12
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