2q32 Deletion (Vascular Ehlers-Danlos Syndrome)

Deletions of 2q32 are not very common, but individuals may present with the well characterized Vascular Ehlers-Danlos Syndrome (vEDS). vEDS is caused by mutations in the COL3A1 gene, which is located within the 2q32 region¹. There are several key characteristics of vEDS including vascular and hollow organ complications, skin findings, characteristic facial features, and joint hypermobility². It should be noted that individuals who have deletions of the COL3A1 gene tend to have more mild clinical symptoms when compared to those with mutations within the COL3A1 gene². Although severe symptoms such as vascular or organ complications are possible, they occur at a lower frequency in those with vEDS due to 2q32 deletions².

One of the most common, and potentially severe, manifestations of vEDS are complications with the vascular system and hollow organs. Vascular complications including aortic dissection, aortic dilations, varicose veins, easy bleeding and bruising are all commonly seen^1,2. Oftentimes, individuals with vEDS may present with vascular complications early in life (some as early as their teens), but these findings are not as commonly seen in those with deletions of 2q32². Additionally, there is concern for hollow organ fragility. This may cause features like colon perforation, collapsed lung, or uterine rupture during pregnancy^1,2.

Although vascular and organ complications are potentially the most severe, it is also common for individuals with vEDS to present with various skin findings. These findings may include thin, translucent skin, hyper-elastic skin, abnormal scarring¹. Although vascular complications are less commonly seen in those with 2q32 deletions, thin or translucent skin is commonly seen³.

It is possible for some individuals with 2q32 deletions to present with facial features that are typically seen in individuals with vEDS. This may include a delicate midface, thin lips, attached earlobes, prominent eyes, thin or pinched nose².

Joint hypermobility is a common clinical finding of several subtypes of Ehlers-Danlos Syndrome. While some subtypes, such as classical EDS, present with more generalized joint hypermobility, vEDS more commonly presents with small joint hypermobility².

References

¹Kempers MJ, Wessels M, Van Berendoncks A, et al. (2022). Phenotype of COL3A1/COL5A2 deletion patients. Eur J Med Genet. 65(10):104593.
²Green CE, Albaba S, Sobey GJ, et al. (2025). Vascular Ehlers Danlos Syndrome and Chromosome 2q32 Microdeletion Syndrome. Eur J Hum Genet. Published online April 17, 2025.
³Meienberg J, Rohrbach M, Neuenschwander S, et al. (2010). Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency. Eur J Hum Genet. 18(12):1315–1321.