Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome

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Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant monogenic COL4A1-related disorder.

Epidemiology

The exact prevalence is unknown.

Clinical presentation

The cardinal features of HANAC syndrome are helpfully described in the name of the condition:

  • hereditary angiopathy: small vessel disease of the brain, generally asymptomatic with no strokes
  • nephropathy: nephritis with hematuria, renal cysts may also be present (which may or may not be symptomatic) 
  • aneurysms: intracranial aneurysms, generally are small and do not rupture
  • muscle cramps: earliest manifestation and can affect any muscle

In addition to the HANAC features, and similar to COL4A1 brain small-vessel disease, additional body systems may also be involved, including the eyes (bilateral retinal artery tortuosity, cataracts, retinal hemorrhages), extracranial vasculature (Raynaud phenomenon), and heart (arrhythmias) .

Pathology

HANAC syndrome is an autosomal dominant condition resulting from a mutation to the COL4A1 gene, located on the long arm of chromosome 13, that normally encodes for the alpha-1 chain of type IV collagen . Type IV collagen is an important component of basement membranes in many tissues, as demonstrated by the wide variety of body systems involved in this condition .

Radiographic features

Imaging is generally only remarkable for CNS manifestations .

CT

CT is non-specific, demonstrating white matter regions of low attenuation .

MRI

MRI is the investigation of choice and demonstrates widespread confluent, bilateral, symmetric white matter hyperintensities on T2-weighted sequences, with relative sparing of subcortical U-fibers . There may be additional features less commonly seen, including dilated perivascular spaces and cerebral microhemorrhages . Evidence of intracerebral macrohaemorrhage, ischemic stroke, or porencephaly is generally not seen in HANAC syndrome .

CTA / MRA

Angiographic studies may demonstrate the presence of intracranial cerebral aneurysms, most commonly affecting the intracranial portion of the internal carotid artery .

Treatment and prognosis

No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended .