Genomics of Fibromuscular Dysplasia

Abstract

Fibromuscular Dysplasia (FMD) is “an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries” (Persu, et al; 2014). FMD can lead to hypertension, arterial dissections, subarachnoid haemorrhage, stroke or mesenteric ischemia. The pathophysiology of the disease remains elusive. While familial cases are rare (<5%) in contemporary FMD registries, there is evidence in favour of the existence of multiple genetic factors involved in this vascular disease. Recent collaborative efforts allowed the identification of a first genetic locus associated with FMD. This intronic variant located in the phosphatase and actin regulator 1 gene (PHACTR1) may influence the transcription activity of the endothelin-1 gene (EDN1) located nearby on chromosome 6. Interestingly, the PHACTR1 locus has also been involved in vascular hypertrophy in normal subjects, carotid dissection, migraine and coronary artery disease. National and international registries of FMD patients, with deep and harmonised phenotypic and genetic characterisation, are expected to be instrumental to improve our understanding of the genetic basis and pathophysiology of this intriguing vascular disease.

Unifocal and Multifocal Fibromuscular Dysplasia

“…The second point is that with Dr. Jean-Philippe Lengelé (GHDC/UCL), we recently described three sisters with renal artery FMD, two have clear multifocal FMD and one has a focal stenosis on one side and on the other side mild irregularities compatible with multifocal FMD. 4 So, I think the association is rare, but it does exist. Also, I am aware of at least one family from Paris in which one sib had multifocal FMD and the other unifocal FMD.…”

Identical Horner Syndrome in Homozygotic Twins Caused by Non-Traumatic Internal Carotid Artery Dissection

“…9,11 A recent genome-wide association study found one risk locus (at PHACTR1) and three other candidate loci for CAD. 12 Interestingly, the locus at PHACTR1 is, among other disorders, also a known risk factor for fibromuscular dysplasia, 13 which is present in 3-15% of CAD patients. 5 Reports have been published both of a familial occurrence of spontaneous CAD and of redissection in patients without known underlying arteriopathies.…”

Case Report and Review of the Literature: Fatal Reversible Cerebral Vasoconstriction Syndrome

“…Cerebrospinal fluid (CSF) analysis revealed high red blood cells (11'200/mm3), moderate elevation of protein level (0.94 g/L; <0.45) and normal white blood cells (0/mm3; <5). According to the international classification of headache disorders (ICHD3), we assumed the diagnosis of RCVS ( 4 ) and a calcium channel blocker therapy was started (nimodipine 30 mg tid orally). On Day 10, because of intracranial vasoconstrictions on transcranial Doppler (TCD) (mean cerebral blood flow velocities (mCBFV) in the right MCA at 200 cm/s and Lindegaard Index at 4.76), nimodipine was increased to 60 mg q.4h ( Figure 3 ).…”