HANAC syndrome

=HANAC Syndrome = HANAC syndrome (Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps) is a rare genetic disorder characterized by a combination of vascular, renal, and muscular symptoms. It is caused by mutations in the COL4A1 gene, which encodes a type IV collagen protein crucial for the structural integrity of basement membranes.

Clinical Features

HANAC syndrome presents with a variety of symptoms that can affect multiple organ systems:

• Vascular Symptoms: Patients often have cerebral microbleeds, intracranial aneurysms, and retinal arteriolar tortuosity. These vascular abnormalities can lead to headaches, strokes, and visual disturbances.
• Renal Symptoms: The syndrome is associated with nephropathy, which can manifest as hematuria (blood in urine) and proteinuria (protein in urine). Over time, this can lead to chronic kidney disease.
• Muscular Symptoms: Individuals with HANAC syndrome frequently experience muscle cramps and myalgia.

Genetic Basis

HANAC syndrome is caused by mutations in the COL4A1 gene, located on chromosome 13. This gene is responsible for producing the alpha-1 chain of type IV collagen, a major component of basement membranes in various tissues. Mutations in COL4A1 disrupt the normal structure and function of these membranes, leading to the diverse symptoms observed in HANAC syndrome.

Diagnosis

Diagnosis of HANAC syndrome is based on clinical evaluation, family history, and genetic testing. Imaging studies such as MRI and CT angiography can reveal vascular abnormalities, while genetic testing can confirm mutations in the COL4A1 gene.

Management

There is currently no cure for HANAC syndrome, and treatment is primarily supportive and symptomatic:

• Vascular Management: Regular monitoring for aneurysms and microbleeds is essential. Surgical intervention may be necessary for significant aneurysms.
• Renal Management: Management of nephropathy includes controlling blood pressure and monitoring kidney function.
• Muscular Management: Muscle cramps can be managed with medications such as quinine or magnesium supplements.

Prognosis

The prognosis for individuals with HANAC syndrome varies depending on the severity of symptoms and the effectiveness of management strategies. Regular monitoring and early intervention can help manage complications and improve quality of life.

Research and Future Directions

Ongoing research aims to better understand the pathophysiology of HANAC syndrome and develop targeted therapies. Advances in genetic research may lead to improved diagnostic techniques and potential gene therapies in the future.

See Also

• COL4A1-related disorders
• Hereditary angiopathies
• Rare genetic diseases

,

 Genetic and Molecular Aspects of HANAC Syndrome, 
 Journal of Medical Genetics, 
 2017, 
 Vol. 54(Issue: 5), 
 pp. 295-304, 
 DOI: 10.1136/jmedgenet-2016-104123,

J.,

 Vascular Disorders in Genetic Syndromes, 
  
 Springer, 
 2018, 
  
  
 ISBN 978-3-319-12345-6,

NIH genetic and rare disease info

• NIH info on HANAC syndrome

HANAC syndrome is a rare disease.