Andermann syndrome

Children with the symptoms of Andermann Syndrome including low muscle tone, a loss of movement, damage to the nerves responsible for movement and sensation that gets worse over time, missing reflexes, and those who have had an MRI that revealed that they were either missing or had an undeveloped area of tissue that connects the left and right sides of the brain (corpus callosum) would be candidates for SLC12A6 testing to confirm the diagnosis. A genetic professional near you can help to discuss and coordinate testing. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.

Individuals who have symptoms related to Andermann Syndrome will generally have a neurological exam, an MRI of the brain to look at the tissue connecting the left and right sides of the brain (corpus callosum), and electrophysiologic studies to confirm the presence of nerve damage. This is followed by genetic testing to look for changes in the SLC12A6 gene to verify the diagnosis. A genetic professional near you can help to discuss and coordinate testing. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.

Carriers of autosomal recessive conditions such as Andermann Syndrome generally do not show symptoms of the condition and are unaware that they carry a change in the gene responsible. Family members of those who have a relative with Andermann Syndrome may wish to know whether they are carriers of a change in the SLC12A6 gene for family planning purposes.

Popular media sites including Facebook can be great resources for connecting with other families who have children with Andermann Syndrome. There are also online support groups for families with children who have a missing or underdeveloped tissue connecting the left and right sides of the brain (corpus callosum) (https://www.facebook.com/groups/740816569313134/). Muscular Dystrophy Canada has information and support for families with muscular dystrophy including Andermann syndrome.

Popular media sites including Facebook can be great resources for connecting with other families who have children with Andermann Syndrome (ACCPN). Muscular Dystrophy Canada has information and support for families with muscular dystrophy including Andermann syndrome.

The common abbreviation for Andermann Syndrome is ACCPN.

Many people with Andermann Syndrome will live into adulthood with an average life expectancy of 33 years.

Andermann Syndrome is a genetic condition that is characterized by the missing or underdeveloped tissue connecting the left and right sides of the brain (corpus callosum) and progressive damage to the nerves that are responsible for muscle movement and sensation. This condition is most often seen in the Saguenay-Lac-St.-Jean and Charlevoix regions of northeastern Quebec.

The primary features of Andermann syndrome start in infancy. A diagnosis may be suspected because of absent reflexes, poor muscle tone, or limb tremors. Once confirmed, several assessments are made. A developmental assessment to look for any intellectual disabilities or developmental delay, physical therapy review to determine what type of weakness is present, and ongoing visits with a multi-disciplinary team to monitor the progression of weakness, the appearance of joint contractures and scoliosis, and for psychiatric manifestations.

Gene changes in the SLC12A6 gene interrupt the function of a protein that transports potassium (K) and chlorine (Cl). Nonfunctional versions of this protein are believed to interfere with the development of the tissue that connects the left and right sides of the brain (corpus callosum), and the nerves that send signals needed for movement and sensation.

The gene responsible for causing Andermann Syndrome is SLC12A6. This gene is found on the long arm of chromosome 15. Several changes in the SLC12A6 gene have been shown to cause Andermann Syndrome.

The main symptoms of Andermann Syndrome include low muscle tone (hypotonia) presenting in the first year of life, lack of reflexes from infancy, muscle weakness and wasting, tremors, delayed walking until about age 3, loss of the ability to walk by the early teens, drooping eyelids (ptosis), weakness of the muscles in the face, gaze palsy and horizontal involuntary eye movements (nystagmus) abnormal curves in the spine (scoliosis) by the age of 10 years, intellectual disabilities, missing or underdeveloped tissue connecting the left and right sides of the brain (corpus callosum), and seizures (epilepsy).

After an initial diagnosis of Andermann syndrome, individuals are sent to a multi-disciplinary team made up of a medical geneticist, pediatrician or pediatric neurologist, an orthopedist, a physiotherapist, and an occupational therapist. Evaluations will be done routinely over time, and include a developmental assessment, physical therapy, and team consultation. The developmental assessment determines the baseline of where the child is at in terms of intellectual and developmental milestones and to determine the presence of delays, and monitors progress. The physical therapy assessment determines weakness and presence of contractures, and identifies treatments. The team will routinely monitor for other symptoms involving the face, such as eye problems, curvature of the spine, and psychiatric disturbances.

The severity of Andermann Syndrome may vary from person to person depending on how much of the tissue that connects the left and right sides of the brain is missing or underdeveloped.

Andermann Syndrome is not currently available on newborn screening. However, children with symptoms of Andermann Syndrome should have a neurological exam, an MRI of the brain, tests to look for nerve damage and subsequent genetic testing.

Andermann Syndrome is caused by gene changes in the SLC12A6 gene. For families of French-Canadian origin, testing can be done to look for specific changes in the gene that are known to be in those populations. For people of other ethnic backgrounds, looking at the entire gene may be more helpful.

As of June 2019, there are no clinical trials ongoing for Andermann syndrome. However, there were research studies being conducted to better understand corpus callosum abnormalities. You can learn more about clinical trials and monitor for the start of any trials by visiting clinicaltrials.gov.

There is currently no cure for Andermann Syndrome. Treatment is supportive and based on symptoms. Treatment may include aids to assist in walking such as canes or wheelchairs, early development and educational intervention, and surgery to fix the abnormal curves in the spine (scoliosis), and sometimes medication for psychiatric symptoms if they develop.

Changes in the SLC12A6 gene have been shown to cause Andermann Syndrome by disrupting a protein that helps to develop nerve tissue.

Having a mutation in SLC12A6 gene that causes lack of functional protein guarantees that an individual will have the signs and symptoms of Andermann Syndrome. Several changes in the gene have been discovered and cause a shorter than normal protein. All of these changes have caused Andermann Syndrome and were inherited in an autosomal recessive pattern, meaning that both copies of the gene carried the change.

Following diagnosis, a child with Andermann should have an evaluation by a medical geneticist, an assessment by a physical therapist, and a developmental assessment. Physical therapy may be helpful in maintaining movement as long as possible. Additionally, a psychiatrist should be seen to monitor, diagnose and treat any psychiatric episodes that the child may experience as they get older. An orthopedist may also be helpful to diagnose and treat the scoliosis that can develop as a result of the muscle and nerve damage. A neurologist should also be seen.

That treatment for Andermann Syndrome is supportive and care is best provided when approached by several different physicians including a pediatric neurologist, occupational and physical therapist, psychiatrist, and orthopedist.

Andermann Syndrome is inherited in an autosomal recessive pattern, meaning that both parents of the child likely carry a change in the SLC12A6 gene. Each pregnancy between the parents of the affected child will have a 25% (1 in 4) chance of receiving two copies of the gene change causing them to have Andermann Syndrome. Approximately 50% (1 in 2) of the children between the parents of the affected child would have one copy of the change making them carriers and likely unaffected, while 25% (1 in 4) of children would have two normal copies of the gene.

Andermann Syndrome is inherited in an autosomal recessive pattern, meaning that both copies of the SLC12A6 gene in cells carry the gene change. The parents of children with autosomal recessive conditions each carry one copy of the gene change but usually do not show signs of the condition themselves. If both parents carry a change in the SLC12A6 gene, each pregnancy between the parents of the affected child will have a 25% (1 in 4) chance of receiving two copies of the gene change causing the baby to have Andermann Syndrome. Approximately 50% (1 in 2) of the children between the parents of the affected child would have one copy of the change making them carriers and likely unaffected, while 25% (1 in 4) of children would have two normal copies of the gene.

While there isn’t an organization specific to Andermann Syndrome, donations can be made to support families with children who have a missing or undeveloped tissue connecting the left and right sides of the brain (corpus callosum) that occurs in most people with Andermann Syndrome. Donations can be made to the National Organization for Disorders of the Corpus Callosum (http://nodcc.org/donate-to-nodcc/).

Clinical research trials can be found by searching for ‘Andermann Syndrome’ on www.clinicaltrials.gov.

While there are not any centers of excellence in Andermann Syndrome in the United States, there are doctors who are familiar with treating those with a missing or underdeveloped tissue connecting the left and right sides of the brain (agenesis or the corpus callosum), which is a primary feature of the condition. One the best ways to find a doctor familiar with Andermann Syndrome care is to talk with other parents of children with the condition.

Researchers who are interested in Andermann Syndrome include Nicolas Dupré in Quebec City, Canada and Guy A Rouleau in Montreal, Canada.

Andermann Syndrome is most common in French Canadian populations in a northwestern region of Quebec. In this area, the condition occurs in approximately 1 in 2,000 births. Andermann Syndrome is rarely seen in other areas of the world. In 2019 there was a case reported in a Roma individual in Bulgaria suggesting that Andermann Syndrome may be more common in this population. However, further studies are required to confirm this.

Children who have symptoms related to Andermann Syndrome will generally have a neurological exam, an MRI of the brain to look at the tissue connecting the left and right sides of the brain (corpus callosum), and electrophysiologic studies to confirm the presence of nerve damage followed by genetic testing to look for changes in the SLC12A6 gene.

There are no known lifestyle or medical risk factors that make the condition worse.

In their 20’s, many people with Andermann Syndrome will develop psychiatric manifestations such as hallucinations, depression, delusions, or “autistic-like” behavior that should be evaluated by a psychiatrist.

Treatment for Andermann Syndrome is supportive and based on symptoms. Treatment may include aids to assist in walking such as canes or wheelchairs, early development and educational intervention, surgery to fix the abnormal curves in the spine (scoliosis), and psychiatric treatment.

Andermann Syndrome is known by several other names including:

One or two “odd” or “unusual” symptoms or clinical features of Andermann Syndrome include the missing or underdeveloped tissue connecting the left and right sides of the brain (corpus callosum) and damage to the nerves that are responsible for movement and sensation resulting in the loss of the ability to walk and normal reflexes.

Popular media sites including Facebook can be great resources for connecting with other families who have children with Andermann Syndrome. There are also online support groups for families with children who have a missing or underdeveloped tissue connecting the left and right sides of the brain (corpus callosum) (https://www.facebook.com/groups/740816569313134/). The University of Maine has an online discussion group and provides information about those with a missing or underdeveloped corpus callosum that can be signed up for at https://umaine.edu/edhd/research/acc/networking-opportunities/. In addition, Muscular Dystrophy Canada has information and support for families with muscular dystrophy including Andermann syndrome.

The symptoms of Andermann Syndrome usually begin in infancy and worsen as the person gets older. Most people with Andermann Syndrome have to use orthotics to help with mobility in their teens, a wheelchair by the time they turn 20 years old and life expectancy is in the late thirties. There are no known variations of this pattern of earlier or later onset for this disease.

Individuals with Andermann syndrome have abnormal or absent reflexes and weak muscle tone. They may experience muscle wasting with progressive weakness, loss of feeling in their arms and legs, and have rhythmic shaking (tremors). Individuals learn to walk, often late, between ages 3 and 4, but lose this ability by adolescence. If the cranial nerves are impacted, the facial muscles may be weak. Eyelids may droop (ptosis) and eyes may not track objects well. Joint contractures occur as affected individuals get older. Many develop curvature of the spine (scoliosis), which may require surgery to correct.

Other physical features may include widely spaced eyes (hypertelorism); a short skull (brachycephaly); a higher than normal hard palate in the mouth; a big toe that crosses over the other toes; and partially fused second and third toes (syndactyly).

Individuals usually have intellectual disabilities, which range from mild to severe. Some experience seizures.

Many of the symptoms that occur in Andermann Syndrome can occur by themselves. Other hereditary motor and sensory neuropathies may look similar to Andermann Syndrome. These include Charcot-Marie Tooth Type IV, Infantile neuroaxonal dystrophy, Arylsulfatase A deficiency, Giant axonal neuropathy, and Spastic paraplegia Type 11.