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

• Agenesis of Corpus Callosum with Peripheral Neuropathy (ACCPN)
• Charlevoix Disease
• Polyneuropathy, Sensorimotor, with or without Agenesis of the Corpus Callosum

What is Andermann Syndrome? (Definition/Background Information)

• Andermann Syndrome (AS) is a disorder that damages the nerves used for muscle movement and sensation (motor and sensory neuropathy). Agenesis or malformation of the corpus callosum also occurs in most people with this disorder
• Signs and symptoms of Andermann Syndrome include areflexia; hypotonia; amyotrophy; severe progressive weakness and loss of sensation in the limbs; and tremors
• Affected individuals of Andermann Syndrome typically begin walking late and lose this ability by their teenage years
• Other features of Andermann Syndrome may include intellectual disability, seizures, contractures, scoliosis, various psychiatric symptoms, various atypical physical features, and cranial nerve problems that cause facial muscle weakness, ptosis, and difficulty following movements with the eyes (gaze palsy)
• Andermann Syndrome is caused by mutations in the SLC12A6 gene and is inherited in an autosomal recessive manner
• Andermann Syndrome is associated with a shortened life expectancy, but affected individuals typically live into adulthood

(Source: Andermann Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Andermann Syndrome? (Age and Sex Distribution)

• Andermann Syndrome is a rare congenital disorder, most prevalent in the French-Canadian population of the Saguenay-Lac-St.-Jean and Charlevoix regions of northeastern Quebec, affecting one in every 2,000 newborns. The occurrence in rest of the world is infrequent
• The onset of disease symptoms may occur at birth
• Both males and females may be affected

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

• A positive family history may be an important risk factor, since Andermann Syndrome can be inherited
• Children of consanguineous parents may bear an increased risk of being born with this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s 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 Andermann Syndrome? (Etiology)

Andermann Syndrome is caused by mutation(s) in the SLC12A6 gene.

• This gene codes for the potassium-chloride (K-Cl) cotransporter, known as cotransporter KCC3, involved in the movement of the charged potassium and chloride ions across cell membranes
• A mutation in this gene is believed to interfere with the development of corpus callosum as well as maintenance of nerves involved in the transmission of signals for movement and sensation
• The condition is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Andermann Syndrome?

The signs and symptoms of Andermann Syndrome may include:

• 2-3 toe syndactyly
• Areflexia
• Brachycephaly
• Decreased motor nerve conduction velocity
• Decreased sensory nerve conduction velocity
• EMG: chronic denervation signs
• Facial asymmetry
• Facial diplegia
• Hypertelorism
• Hypoplasia of the maxilla
• Limb muscle weakness
• Limb tremor
• Long face
• Macrotia
• Motor delay
• Motor polyneuropathy
• Neonatal hypotonia
• Onion bulb formation
• Peripheral axonal neuropathy
• Polyneuropathy
• Psychosis
• Respiratory tract infection
• Restrictive deficit on pulmonary function testing
• Sensory neuropathy
• Skeletal muscle atrophy
• Tapered finger
• Ventriculomegaly
• Wide nasal bridge

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Agenesis of corpus callosum
• EEG abnormality
• Hemiplegia/hemiparesis
• Intellectual disability
• Microcephaly
• Seizures

Frequently present symptoms in 30-79% of the cases may include aqueductal stenosis.

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of retinal pigmentation
• Myopia
• Nystagmus
• Strabismus
• Turricephaly

(Source: Andermann Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Andermann Syndrome Diagnosed?

Andermann Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative mutation(s) in the SLC12A6 gene

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 Andermann Syndrome?

The complications of Andermann Syndrome may include:

• Severe intellectual disability
• Risk of fall injuries due to seizures
• Progressive worsening of motor functions
• Loss of mobility (incapability of walking)
• Poor quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Andermann Syndrome Treated?

There is no cure for Andermann Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Andermann Syndrome be Prevented?

Currently, Andermann Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, 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

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

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

• The prognosis of Andermann Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Andermann Syndrome:

Andermann Syndrome is also known by the following names:

• Agenesis of Corpus Callosum with Neuronopathy
• Agenesis of Corpus Callosum with Polyneuropathy
• Corpus Callosum Agenesis Neuronopathy
• Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC)

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/