Is fibromuscular dysplasia (FMD) a genetically transmitted disease?

Fibromuscular Dysplasia Is Not Primarily a Genetic Disease

Fibromuscular dysplasia (FMD) is not considered a primarily genetically transmitted disease, although there may be a genetic component in some cases with a familial occurrence rate of approximately 10%. 1 The etiology of FMD remains largely unknown despite various theories involving hormonal, mechanical, and genetic factors.

Genetic Aspects of FMD

• FMD is suspected to have some genetic influence as it primarily affects Caucasians 2
• An association between FMD and the HLA-DRw6 histocompatibility antigen has been described 2
• Unlike conditions with clear genetic inheritance patterns, FMD does not follow a specific inheritance pattern in most cases
• The majority of FMD cases appear to be sporadic rather than hereditary

Epidemiology and Risk Factors

• FMD predominantly affects women, particularly middle-aged Caucasian females 3, 1
• The prevalence of symptomatic renal artery FMD is approximately 4/1000, with cervicocranial FMD about half that rate 1
• FMD is a nonatherosclerotic, noninflammatory vascular disease that can affect medium-sized muscular arteries throughout the body 4
• The disease most commonly involves renal and cerebrovascular arteries but can affect virtually any arterial bed 4

Pathophysiology

• FMD is characterized by stenosis due to thickening of the arterial wall 3
• Histological classification includes three main subtypes: intimal, medial, and perimedial 1
• Angiographic classification includes:
  • Multifocal type (most common, >80% of cases) with the characteristic "string-of-beads" appearance
  • Tubular type
  • Focal type 1
• The disease appears to be systemic, with subclinical lesions found at arterial sites distant from the stenotic arteries 1, 4

Clinical Manifestations

• Clinical manifestations depend on the affected arterial beds:
  • Renal artery involvement (most common): renovascular hypertension
  • Cervicocranial involvement: headache, Horner's syndrome, stroke, or intracerebral aneurysms with risk of hemorrhage
  • Other manifestations: abdominal angina or claudication of extremities 5
• FMD can be complicated by arterial dissection, aneurysm formation, and arterial tortuosity 4

Diagnostic Approach

• Noninvasive diagnostic tests include ultrasonography, magnetic resonance angiography, and computed tomography angiography 1
• The gold standard for diagnosis is catheter angiography, though this is typically reserved for cases where revascularization may be performed during the same procedure 1
• Differential diagnosis includes atherosclerotic stenoses and stenoses associated with vascular Ehlers-Danlos syndrome, Williams syndrome, and type 1 neurofibromatosis 1

Management Considerations

• Treatment is generally reserved for symptomatic cases 2
• For renovascular hypertension, management includes:
  • Antihypertensive therapy
  • Percutaneous angioplasty for severe stenoses
  • Reconstructive surgery for complex FMD extending to segmental arteries 1
• For cerebrovascular complications such as aneurysms, options include microvascular neurosurgical clipping and endovascular coiling 1
• Corticosteroids should be avoided as they can directly harm the vascular wall and aggravate lesions in FMD 2

Relationship to Connective Tissue Disorders

• Some FMD patients exhibit connective tissue features such as moderately severe myopia, high palate, dental crowding, and early-onset arthritis 6
• Patients with a high vascular risk profile (≥1 dissection and/or ≥2 aneurysms) have higher rates of spontaneous pneumothorax and atrophic scarring 6
• However, no characteristic connective tissue phenotype has been definitively associated with FMD 6

In conclusion, while there may be a genetic component to FMD in some cases, current evidence does not support classifying it as a primarily genetically transmitted disease. The etiology appears to be multifactorial, likely involving a combination of genetic predisposition and environmental factors.