MRI of great vessel morphology and function in Ehlers-Danlos syndrome type IV

Abstract

The purpose of this study was to investigate whether large arteries in subjects with Ehlers-Danlos Syndrome Type IV (EDS IV) exhibit altered morphological and functional characteristics that might indicate the risk of complications. Subjects with EDS IV, an inherited disorder of type III collagen, have a significant lifetime risk of arterial rupture. Magnetic Resonance Imaging (MRI) of the aorta and carotid artery was used to measure diameter, wall thickness, pulse propagation velocity, and spin-spin relaxation time constant (T(2)) of the artery walls. These measurements were made and compared by a two-sided t-test in 17 subjects with EDS IV and in eight age and gender matched sibling controls. Additionally, Spearman correlation was computed between measurements and the average longevity of affected relatives. Comparing controls to 15 subjects with no known prior aortic complications, we found no differences in the diameters of the descending thoracic and abdominal aortas, but did find ascending aorta dilatation in two subjects (13%). We also found a trend in EDS IV subjects toward higher wall thicknesses after normalizing by body surface area for both the abdominal aorta (P=0.05) and the common carotid artery (P=0.07). Finally, we found a significant negative correlation (R= -0.82, P=0.02) between age-adjusted pulse propagation velocity and familial longevity. In conclusion, preliminary evidence suggests that elevated pulse propagation velocity, which indicates reduced vessel distensibility, may be a risk factor for complications of EDS IV. Ascending aorta dilatation and increased vessel wall thickness were also found in subjects with EDS IV and represent potential risk factors for future study.

Clinical, structural, biochemical and X‐ray crystallographic correlates of pathogenicity for variants in the C‐propeptide region of the COL3A1 gene

“…Both these reports illustrate the use of structural data in the interpretation of genomic and sequence variants in human disease. With regard to missense variants in the C‐propeptide of COL3A1 , in addition to those presented here and already discussed [Bourhis et al, ], two variants have been found in the region of the Ca 2+ binding site (p.Gly1284Glu [Jørgensen et al, ]; p.Asp1288Val [Kerwin et al, ]), both of which affect trimerization leading to reduced amounts of procollagen III. Furthermore, another sequence variant (p.Pro1440Ser, similar to Patient 1) has also been reported [Morissette et al, ], though the biochemical consequences have not been described.…”

Compliance and pulse wave velocity assessed by MRI detect early aortic impairment in young patients with mutation of the smooth muscle myosin heavy chain

“…In our study, PWV was considered as the distance between two points divided by the time needed for the pulse wave to cover this distance. Similar methods also using magnetic resonance imaging have previously been described (13,16,17,32,33). The principal difference between the proposed methods is the determination of the transit time for the flow wave to propagate from one point to another.…”

Aortic Stiffness

“…The vascular type of Ehlers-Danlos is a rare disease presenting as spontaneous arterial rupture usually without dissection (56). A small study using MRI showed that AD was reduced, whereas aortic wall thickness was slightly increased, although only 9 of 15 subjects had interpretable images (57). After aortic coarctation repair.…”