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.
The exact prevalence is unknown.
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.
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.
Imaging is generally only remarkable for CNS manifestations 1-3.
CT is non-specific, demonstrating white matter regions of low attenuation 1,2.
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
Treatment and prognosis
No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended 1.
- 1. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, Marro B, Desmettre T, Cohen SY, Roullet E, Dracon M, Fardeau M, Van Agtmael T, Kerjaschki D, Antignac C, Ronco P. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. The New England journal of medicine. 357 (26): 2687-95. doi:10.1056/NEJMoa071906 - Pubmed
- 2. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology. 73 (22): 1873-82. doi:10.1212/WNL.0b013e3181c3fd12 - Pubmed
- 3. Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain. American journal of medical genetics. Part A. 152A (10): 2550-5. doi:10.1002/ajmg.a.33659 - Pubmed