Carriers of COL3A1 pathogenic variants in Denmark: Interfamilial variability in severity and outcome of elective surgical procedures

• Published in: Clinical genetics 2022-09, Vol.102 (3), p.191-200
• Main Authors: Sølyst, Sofus, Oksjoki, Riina, Farholt, Stense, Nielsen, Dorte Guldbrand, Christensen, Alex H., Fagerberg, Christina R., Risom, Lotte, Gregersen, Pernille Axél, Christensen, Maria Bejerholm, Rasmussen, Torsten Bloch, Diness, Birgitte Rode
• Format: Article
• Language: English
• Subjects: COL3A1; Ehlers-Danlos syndrome; genotype–phenotype; Medical records; Patients; Phenotypes; surgical complications; vascular EDS; vascular Ehlers–Danlos syndrome; vEDS
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.14176

The study describes all patients in Denmark with vascular Ehlers–Danlos syndrome (vEDS). Carriers of pathogenic or likely pathogenic COL3A1 variants were retrospectively identified through registries and specialized clinics. Medical records were reviewed for vascular‐ or organ ruptures and invasive procedures performed. Identified families were divided by variant type (null, splice, and missense) and familial phenotypes (severe or attenuated). Families in which at least one carrier has suffered a major event before the age of 30 were classified as severe, whereas families in which at least three carriers had reached the age of 40 without a major event were classified as attenuated. Eighty‐seven persons (59 still alive) from 25 families were included with a mean observation time of 44 years. Sixty‐seven percent of patients could be subclassified in a familial phenotype. Thirty‐one major events were observed. Eleven complications in 172 invasive procedures were recorded. No fatal complications to elective surgery were observed. The type of COL3A1 variant did not reliably predict phenotype, but a pattern of intrafamilial consistency emerged with some families showing an attenuated form of vEDS. Elective medical procedures appear to be safer than previously thought, although data only allow for conclusions regarding individuals from families with the attenuated form of vEDS. We report on all known Danish cases of Vascular Ehlers–Danlos Syndrome (87 individuals from 25 families). Main findings: Some families have a severe phenotype (at least one carrier had a major event before the age of 30 years), whereas other families seem to have an attenuated phenotype (at least three carriers reached the age of 40 years without a major event). The type of COL3A1 variant did not reliably predict severity No fatal complications to 125 elective medical procedures were observed