- 1st Abstract
at the American Society of Human Genetics Annual Meeting, Oct. 2006
A cohort of patients with generalized Fibromuscular Dysplasia
and features of Ehlers-Danlos Syndrome:
A new phenotype. N.B. McDonnell1, J. Yang1,
W. Chen1, B. Griswold1, C.A. Francomano1,2. 1) National Institute
on Aging, NIH, Baltimore, MD; 2) Harvey Inst Human Gen, Greater
Baltimore Medical Center, Baltimore, MD.
Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary
disorders of connective tissue. Vascular dissections and aneurysms
are a cardinal feature of the vascular form of EDS (VEDS) caused
by mutations in COL3A1. Loeys-Dietz syndrome, a closely related
phenotype, is caused by mutations in TGFBR1 or TGFBR2. We have identified
a group of patients without mutations in COL3A1, TGFBR1 or TGFBR2
who presented with arterial dissections and aneurysms as well as
stenotic lesions with a diagnosis of fibromuscular dysplasia (FMD)
by pathology or radiology. Varying features of Ehlers-Danlos syndrome,
such as atrophic scars, velvety or stretchy skin, joint hypermobility
as evidenced by a high Beighton score, history of articular dislocations,
uterine prolapse, joint pain, pectus deformities, pes planus and
scoliosis were also present. Several of the patients had a family
history of premature death from vascular events, as well as a family
history of joint and skin abnormalities compatible with an autosomal
dominant inheritance pattern. There were no reports of uterine or
bowel rupture, or pregnancy related death in personal or family
histories. The facial features were not characteristic of VEDS or
Loeys-Dietz syndrome. The first patient identified was a 44 year
old woman who had a history of carotid dissection, ruptured cerebral
aneurysms, FMD of renal arteries and iliac vessels, multiple atrophic
scars, frequent joint dislocations, and stretchy and doughy skin.
A cohort of thirty patients with this syndrome has been identified
and detailed phenotype and family history information has been assembled.
The etiology of fibromuscular dysplasia is thought to be heterogeneous,
with genetic and environmental factors proposed as possible contributors.
Our findings suggest that there is a previously unrecognized variant
of EDS, distinct from the VEDS and Loeys-Dietz syndrome, with FMD
as a major clinical feature in addition to the skin and joint abnormalities.