Leukodystrophy - adult onset

Gene: C1R

I don't know

Classic periodontal EDS (pEDS) phenotype is associated with gain-of-function mutations in this gene (Kapferer-Seebacher, van Dijk, and Zschocke, GeneReviews, 2021). Earlier case reports noted the presence of leukodystrophy in one 37-year-old female with clinically-diagnosed pEDS (PMID: 8958339) and eight adult individuals from two families with heterozygous mutations in C1R (PMID: 30535813), where other causes of leukodystrophy were ruled out or considered unlikely. Recent data presented at the 2022 EDS International Scientific Symposium by Angwin et al (Oral Abstract 91) highlighted nine more adults with clinically and molecularly confirmed pEDS with evidence of leukodystrophy (out of ten such patients with available imaging). Nearly all patients reported to date have no cognitive deficits or other neurological features of leukodystrophy, with only isolated cases of recurrent headaches/drop attacks or mild cognitive decline/ataxia that might have a different aetiology. Pathophysiology is thought to result from underlying small vessel disease (similar in pattern to that of CADASIL) which progresses with age and is disproportionate to the observed neurological phenotype in these individuals.
Sources: Literature, Other

Created: 21 Sep 2022, 3:34 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080); Leukodystrophy - adult onset

Publications

• 8958339
• 30535813

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments