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Open Access 01-03-2019 | Original Article

Periodontal Ehlers–Danlos syndrome is associated with leukoencephalopathy

Authors: Ines Kapferer-Seebacher, Quinten Waisfisz, Sylvia Boesch, Marieke Bronk, Peter van Tintelen, Elke R. Gizewski, Rebekka Groebner, Johannes Zschocke, Marjo S. van der Knaap

Published in: Neurogenetics | Issue 1/2019

Abstract

Here, we report brain white matter alterations in individuals clinically and genetically diagnosed with periodontal Ehlers–Danlos syndrome, a rare disease characterized by premature loss of teeth and connective tissue abnormalities. Eight individuals of two families clinically diagnosed with periodontal Ehlers–Danlos syndrome were included in the present study and underwent general physical, dental, and neurological examination. Whole exome sequencing was performed, and all patients included in the study underwent MRI of the brain. Whole exome sequencing revealed heterozygous C1R mutations c.926G>T (p.Cys309Phe, Family A) and c.149_150TC>AT (p.Val50Asp, Family B). All adult individuals (n = 7; age range 31 to 68 years) investigated by MRI had brain white matter abnormalities. The MRI of one investigated child aged 8 years was normal. The MRI pattern was suggestive of an underlying small vessel disease that is progressive with age. As observed in other leukoencephalopathies related to microangiopathies, the extent of the white matter changes was disproportionate to the neurologic features. Medical history revealed recurrent headaches or depression in some cases. Neurological examination was unremarkable in all individuals but one had mild cognitive decline and ataxia and experienced a seizure. The observation that periodontal Ehlers–Danlos syndrome caused by missense mutations in C1R is consistently associated with a leukoencephalopathy opens a new pathogenic link between the classical complement pathway, connective tissue, brain small vessels, and brain white matter abnormalities.

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Title: Periodontal Ehlers–Danlos syndrome is associated with leukoencephalopathy
Authors: Ines Kapferer-Seebacher
Quinten Waisfisz
Sylvia Boesch
Marieke Bronk
Peter van Tintelen
Elke R. Gizewski
Rebekka Groebner
Johannes Zschocke
Marjo S. van der Knaap
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Published in: Neurogenetics / Issue 1/2019
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-018-0560-x

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Periodontal Ehlers–Danlos syndrome is associated with leukoencephalopathy

Abstract

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Abstract

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