COL3A1 variant implications for first- and second-degree relatives

COL3A1 variant implications for first- and second-degree relatives

This algorithm applies to families in which a familial COL3A1 variant has been identified in one individual. All relatives who carry the variant are at risk for the complications of vascular EDS (VEDS), even if they have not yet developed a vascular or other complication. Any individual with clinical features of VEDS who tests negative for a COL3A1 variant should be evaluated by a genetics expert or disease specialist to determine the appropriate evaluation, which may include additional testing for COL3A1 variants, testing for other disease genes, or additional clinical evaluations. The initial vascular complications of VEDS can be life-threatening, and all individuals with VEDS should be cared for by a multidisciplinary team and evaluated for potential complications. Refer to UpToDate for details of the evaluations and other management recommendations.

* If the parents are not available for testing, the affected individual's siblings and children should be tested.

¶ In mosaicism, a genetic change occurs early in embryogenesis, resulting in some tissues populated by cells that carry the variant and others that do not. If the germ cells (ovaries or testes) carry the variant, an egg or sperm may carry the variant as well. The risk for transmission of the variant depends on the proportion of eggs or sperm that carry the variant; the maximum risk is 50% with each child. Thus, the siblings of an individual with a pathogenic variant in COL3A1 may also carry the variant, even if both parents test negative. The possibility of mosaicism is especially important to consider for COL3A1 variants because affected individuals can be asymptomatic until their initial (possibly catastrophic) presentation in early adulthood.

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COL3A1 variant implications for first- and second-degree relatives