What are the other Names for this Condition? (Also known as/Symptoms)

• Autosomal Dominant Familial Hematuria, Retinal Arteriolar Tortuosity, Contractures
• HANAC Syndrome

What is HANAC Syndrome? (Definition/Background Information)

• Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome (HANAC Syndrome) is a rare genetic disorder. It is caused by a mutation in the COL4A1 gene, which codes for a protein that is a component of collagen. The syndrome is characterized by blood vessel disorders (angiopathy) that affect several parts of the body
• HANAC Syndrome is inherited in an autosomal dominant fashion where a single defective copy of the causative gene is enough to cause the condition. A family history is the single largest risk factor for developing the condition
• Major symptoms of HANAC Syndrome can include muscle cramps, headaches, vision problems, arrhythmia, kidney cysts, change in brain structure and hemorrhagic aneurysms
• Stroke, prolonged muscle cramps, arrhythmia, and mild kidney failure are some of the potential complications associated with Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome
• HANAC Syndrome can be diagnosed with the help of physical examination, symptoms assessment, family history evaluation, blood tests, and imaging studies
• There are currently no treatments available for HANAC Syndrome; however, symptomatic treatments may offer relief to the affected individuals
• Discontinuation of strenuous exercising, smoking, blood thinners and activities that could potentially cause head trauma may help prevent the symptoms of HANAC Syndrome from worsening
• The exact prognosis of HANAC Syndrome is not reported. However, the prognosis depends upon the severity of the signs and symptoms; individuals with mild signs and symptoms have better prognosis than those with severe signs and symptoms

Who gets HANAC Syndrome? (Age and Sex Distribution)

• Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome is a rare genetic disorder with unknown prevalence rate
• Some reports suggest a prevalence of 1 in a million individuals being affected. So far, only 6 affected families have been reported and documented in detail
• HANAC syndrome is reported to manifest during childhood. Most of the signs and symptoms may develop later in one’s life
• Both genders may be affected and no preference is seen
• No racial and ethnic group predilection is also noted

What are the Risk Factors for HANAC Syndrome? (Predisposing Factors)

• Having a family history of Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome is the single largest risk factor for developing of HANAC Syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of HANAC Syndrome? (Etiology)

Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome is caused by mutations in COL4A1 gene.

• Under normal circumstances, the COL4A1 gene codes for a component of type IV collagen
• The type IV collagen molecules bind together to form basement membranes, which provide structural integrity for them and separation between cells in almost all body tissues, including the blood vessels
• When the COL4A1 gene is mutated, the resultant mutated component of collagen IV does not allow the binding with other molecules to happen, compromising the structural integrity of the basement membranes
• The susceptibility of the weakened basement membranes to breaking causes angiopathy (a form of blood vessels disorder), as well as weakening of other tissues and organs, leading to HANAC Syndrome

HANAC Syndrome is inherited in an autosomal dominant fashion, in which a single copy of the defective gene is sufficient to cause the condition.

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of HANAC Syndrome?

Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome is a disorder of the blood vessels (angiopathy) that can also potentially affect multiple tissues. Hence, the following are some of the main signs and symptoms of HANAC Syndrome based on the organs that are affected:

• Kidneys
  • Blood in urine
  • Cysts formation in either one or both kidneys
  • Kidney disease (nephropathy)
• Heart: Supraventricular arrhythmia (irregular heartbeats, owing to the lower chambers of the heart beating rapidly)
• Brain-related:
  • Headaches
  • Intracranial aneurysms (enlargement of one or more blood vessels in the brain)
  • Rarely, hemorrhagic stroke or bleeding in the brain
  • Leukoencephalopathy or change in the white matter of brain causing a variety of neurological signs and symptoms
• Eye-related:
  • Abnormal structure of arteries within the eyes (arterial retinal tortuosity)
  • Bleeding with any minor injury or trauma to the eye
  • Cataracts
  • Tearing of the iris and abnormal positioning of the pupil in the eye (it is not centered). This is collectively known as Axenfeld-Rieger anomaly
• Muscle-related:
  • Cramping that can last for up to several minutes
  • Cramping caused by exercise
• Fingers and toes: Raynaud phenomenon, in which a narrowing of blood vessels in the fingers and toes is brought upon by temperature changes. This may cause tingling or throbbing sensations. The fingers and toes may also turn blue for a short period of time

HANAC Syndrome may initially manifest in some children, only as muscle cramps. Additional symptoms may develop later in life.

How is HANAC Syndrome Diagnosed?

The diagnosis of Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome is made based on the following procedures:

• A physical examination
• An assessment of symptoms
• An evaluation of family medical history
• Blood test to check for serum creatine kinase concentration (to assess muscle breakdown and renal problems)
• Magnetic resonance imaging (MRI) of the brain and kidneys
• Eye examination and vision tests
• Genetic testing: If there is a family history of the condition, prenatal genetic testing of fetal cells may be performed

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of HANAC Syndrome?

Some potential complications from Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome include:

• Muscle cramps that may last for hours
• Stroke (reported in about 5% of the affected individuals)
• Changes in the white matter of brain resulting in severe neurological symptoms
• Temporary vision loss
• Cysts in kidneys may become enlarged, which may lead to mild renal failure
• Cardiac arrhythmia
• The use of blood thinners for any condition, may result in bleeding disorders

How is HANAC Syndrome Treated?

There are currently no treatments available to cure Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome. However, symptomatic treatments and the use of medications may help reduce symptoms and discomfort for the following conditions:

• High blood pressure and arrhythmia
• Headaches
• Muscle cramps

Other treatment measures may include:

• Treating abnormalities in kidney function
• Treating arrhythmias of the heart
• Addressing neurological signs and symptoms caused by brain stroke

How can HANAC Syndrome be Prevented?

• Currently, there are no specific methods or guidelines to prevent Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as HANAC Syndrome

Nevertheless, the following steps may help prevent exacerbation of the condition:

• Avoidance of activities that could cause head trauma
• Smoking cessation
• Avoidance of blood thinners
• Avoiding excessive and/or strenuous physical activity

Regular medical screening at periodic intervals with tests, and physical examinations are strongly recommended.

What is the Prognosis of HANAC Syndrome? (Outcomes/Resolutions)

• The prognosis of Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome is not reported, since it is a very rare disorder
• The outcome may be dictated by the types and severity of signs and symptoms in the affected individuals. Individuals with mild signs and symptoms have better prognosis than those with severe signs and symptoms

Additional and Relevant Useful Information for HANAC Syndrome:

Please visit our Congenital & Genetic Disorders Center for more physician-approved health information:

http://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/