Phenotype of COL3A1/COL5A2 deletion patients

Marlies JE Kempers*, Marja Wessels, An Van Berendoncks, Ingrid MBH van de Laar, Nicole de Leeuw, Bart Loeys

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)


Introduction: The diagnosis of Ehlers-Danlos syndrome is usually based on well-defined diagnostic criteria and the result of DNA investigation. Classical (cEDS) and vascular type (vEDS) are the most prevalent subtypes and are caused by heterozygous pathogenic variants in COL5A1, COL5A2, COL1A1 or, respectively, in COL3A1. We describe 3 cases with contiguous deletions resulting in haploinsufficiency of both genes with relative mild features of connective tissue disease.

Patients and methods: Information on medical history, physical information, genetic results (CNV-analysis) and imaging were obtained from the medical file.

Results: The first patient was a 31 yr old female, diagnosed during pregnancy after the NIPT result showed an interstitial deletion of 2.3 Mb on chromosome 2q32.2, confirmed by XON array. She had normal aortic diameters. She had no signs of cEDS or vEDS except for a relatively thin skin with increased visibility of the veins. Her father died suddenly of a type A/B dissection at the age of 62 years. The second patient was diagnosed at the age of 10 years after she was referred because of her intellectual disability, autism and constipation. She was known with a thin and vulnerable skin and had a bleeding after tooth extraction. Array showed a 14,5 Mb deletion of 2q31.3q32.3 (de novo). Imaging (latest age 17 years) did not show any abnormalities. The third patient, aged 28 years, was diagnosed during pregnancy with an interstitial deletion of circa 6 Mb on chromosome 2q31.1q32.2 3, previously shown in the fetus with bilateral club feet and hydronephrosis. She had no vEDS facial features and the skin was relatively thin. She has thoracolumbar scoliosis and dural ectasia. Imaging did not reveal any vascular abnormalities. Her son, born at 37 weeks 3 days. had club feet but not other clinical signs suggestive of classical or vascular EDS.

Discussion: Three patients are described with a contiguous deletion of varying size encompassing the COL3A1 and COL5A2 gene. Due to the mild phenotype a diagnosis of EDS was not suspected and was found coincidental. Since two of the patients were pregnant without major complications these patients may require a less defensive, approach to pregnancy/delivery.

Original languageEnglish
Article number104593
JournalEuropean Journal of Medical Genetics
Issue number10
Early online date11 Aug 2022
Publication statusPublished - Oct 2022

Bibliographical note

Funding Information:
This publication has been supported by the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) - Project ID: 769036, which is partly co-funded by the European Union within the framework of the Third Health Programme “ERN-2016 - Framework Partnership Agreement 2017–2021.

Publisher Copyright:
© 2022


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