Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome

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 ^1-3
• nephropathy: nephritis with hematuria, renal cysts may also be present (which may or may not be symptomatic) ^1-3
• aneurysms: intracranial aneurysms, generally are small and do not rupture ^1-3
• muscle cramps: earliest manifestation and can affect any muscle ^1-3

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) ^1-3.

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 ^1-3. 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 ^1-3. 

Radiographic features

Imaging is generally only remarkable for CNS manifestations ^1-3.

CT

CT is non-specific, demonstrating white matter regions of low attenuation ^1,2.

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 ^1,2. There may be additional features less commonly seen, including dilated perivascular spaces and cerebral microhemorrhages ². Evidence of intracerebral macrohaemorrhage, ischemic stroke, or porencephaly is generally not seen in HANAC syndrome ^1,2.

CTA / MRA

Angiographic studies may demonstrate the presence of intracranial cerebral aneurysms, most commonly affecting the intracranial portion of the internal carotid artery ^1,2.

Treatment and prognosis

No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended ¹.