TY - JOUR

T1 - Carriers of COL3A1 pathogenic variants in Denmark

T2 - Interfamilial variability in severity and outcome of elective surgical procedures

AU - Sølyst, Sofus

AU - Oksjoki, Riina

AU - Farholt, Stense

AU - Nielsen, Dorte Guldbrand

AU - Christensen, Alex H.

AU - Fagerberg, Christina R.

AU - Risom, Lotte

AU - Gregersen, Pernille Axél

AU - Christensen, Maria Bejerholm

AU - Rasmussen, Torsten Bloch

AU - Diness, Birgitte Rode

N1 - Funding Information: We thank the families involved for their contributions.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - COL3A1

KW - genotype–phenotype

KW - surgical complications

KW - vascular EDS

KW - vascular Ehlers–Danlos syndrome

KW - vEDS

U2 - 10.1111/cge.14176

DO - 10.1111/cge.14176

M3 - Journal article

C2 - 35699227

AN - SCOPUS:85133396947

VL - 102

SP - 191

EP - 200

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 3

ER -