Andermann Syndrome

What Causes Andermann Syndrome?

Andermann syndrome is caused by an abnormal change (mutation) in a gene called the SLC12A6 gene. This gene carries instructions for making a protein vital in the transportation of potassium and chlorine between cells. Although the precise function of the protein is not yet clearly understood, it seems to be critical in the function and health of nerve cells.

Is Andermann Syndrome Hereditary?

Andermann syndrome is an inherited disorder. Most cases are inherited in an autosomal recessive pattern, meaning that a child must inherit two copies of the mutated gene, one from each parent, for the disorder to develop. Parents in these cases carry just one copy of the mutation, so they typically do not show any symptoms of Andermann syndrome themselves.

If both parents carry one of the disorder-causing mutations, they have a 25 percent chance of having a child affected by the disorder with each pregnancy. In 50 percent of their pregnancies, the child will carry the mutation but not develop the condition. In 25 percent of pregnancies, their child will not carry the mutation and will not pass the disorder-causing mutation to their children.

How Is Andermann Syndrome Detected?

The symptoms of Andermann syndrome appear in infancy and progressively worsen into childhood. Early signs of the disorder include:

• Weak muscle tone in infancy
• Delayed walking (usually not until the age of three or four)
• Weak facial muscles
• Drooping eyelids
• Involuntary eye movements
• Progressive loss of mobility

How Is Andermann Syndrome Diagnosed?

A doctor may suspect Andermann syndrome if a child presents symptoms consistent with the disorder, and other potential causes of the symptoms can be ruled out. The diagnostic process may include:

• Assessment of the child’s medical history
• Physical and neurological exams
• Tests of muscle function
• Imaging exams to look for abnormal development of the corpus callosum
• Genetic testing to look for mutations of the SLC12A6 gene

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Andermann Syndrome Treated?

Andermann syndrome has no cure, and no treatment will reverse or stop the progression of its symptoms. Instead, treatment approaches aim to manage symptoms, prevent complications, and improve quality of life. For example, physical therapy may be used to prolong mobility. In some cases, surgery may be required to correct progressive spinal malformations.

How Does Andermann Syndrome Progress?

The symptoms of Andermann syndrome worsen over time. People with the disorder typically lose the ability to walk before the age of 20. Other long-term complications of AS may include:

• Progressive immobility of joints (contractures)
• Deterioration of muscle tissue
• Weakness and loss of sensation in the limbs
• Progressive abnormal curvature of the spine (scoliosis)
• Intellectual disabilities
• Depression or anxiety
• Hallucinations
• Paranoia

People with Andermann syndrome typically survive into adulthood, but their life expectancy is shorter than average. The disorder is often fatal by the age of 40.

How Is Andermann Syndrome Prevented?

There is no known way to prevent Andermann syndrome. Parents with a family history of the disorder or who have had another child with Andermann syndrome are advised to consult a genetic counselor to assess their risk if they plan to have another child.

Andermann Syndrome Caregiver Tips

• Look for help from others who know what you’re going through. Living with Andermann syndrome is much more difficult if you feel like you’re on your own. Online support groups can help by providing you with a community of other people living with similar disorders.  
• Andermann syndrome is rare, and you might have trouble finding information and educational resources about the disorder. However, the National Organization for Disorders of the Corpus Callosum maintains resources to help families understand Andermann syndrome and other ACC disorders.

Some people with Andermann syndrome also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the issues commonly associated with Andermann syndrome and related disorders:

• Some people with Andermann syndrome also suffer from attention-deficit/hyperactivity disorder.
• People with Andermann syndrome are at increased risk of developing some psychotic disorders similar to schizophrenia.
• Autism spectrum disorder may be more common in people with Andermann syndrome.
• People with Andermann syndrome are at increased risk of depression and anxiety.

Andermann Syndrome Brain Science

The SLC12A6 gene contains instructions for the production of a protein called a K-Cl cotransporter. The name refers to the protein’s role in transporting potassium (K) and chlorine (Cl) atoms into and out of cells. Scientists are still working to understand the function of this transport mechanism, but it seems essential in maintaining the health and function of specific nerve tissues. When a mutation in the SLC12A6 gene interferes with the production of functional K-Cl cotransporter proteins, nerve damage may result, leading to the symptoms of Andermann syndrome. The protein also appears crucial for the normal development of the corpus callosum.

Scientists have noted that the SLC12A6 gene lies in a region of chromosome 15 that has also been associated with several psychiatric disorders, including:

• Bipolar disorder
• Autism
• Schizophrenia
• Attention-deficit/hyperactivity disorder

This chromosomal region is also associated with some types of epilepsy.

Andermann Syndrome Research

Title: Brain Development Research Program

Stage: Recruiting

Principal investigator: Elliott H Sherr, MD, PhD

University of California, San Francisco

San Francisco, CA

Dr. Elliott Sherr and his collaborators at the University of California, San Francisco (UCSF) are studying the genetic causes of disorders of cognition and epilepsy, in particular, disorders of brain development that affect the corpus callosum, such as Aicardi syndrome, as well as two additional brain malformations, polymicrogyria and Dandy-Walker malformation. The investigators’ research aims to better understand the underlying genetic causes as a foundation to develop better treatments for these groups of patients.

The team is studying both the genetics and clinical features of these disorders. They hope to understand the problems faced by individuals with these disorders as well as their causes. In the future, they hope to develop therapies that are geared specifically for individuals based on the underlying biology. To participate in the study, candidates will be asked to provide a copy of the magnetic resonance imaging (MRI) documenting Agenesis Corpus Callosum (ACC), Polymicrogyria (PMG), or Dandy-Walker malformation (DWM), clinical information, and saliva or blood samples from the affected individual and the parents.

Title: Human Epilepsy Genetics–Neuronal Migration Disorders Study

Stage: Recruiting

Principal investigator:  Christopher A. Walsh, MD, PhD

Boston Children’s Hospital

Boston, MA

Epilepsy is responsible for tremendous long-term healthcare costs. Analysis of inherited epilepsy conditions has allowed for the identification of several key genes active in the developing brain. Although many genetic abnormalities of the brain are rare and lethal, rapidly advancing knowledge of the structure of the human genome makes it a realistic goal to identify genes responsible for several other epileptic conditions.

This study aims to identify genes responsible for epilepsy and disorders of human cognition (EDHC). The Walsh Laboratory at the Children’s Hospital Boston and Beth Israel Deaconess Medical Center is looking for genes involved in brain development. Conditions that they study include brain malformations, such as polymicrogyria, lissencephaly, Walker-Warburg syndrome, heterotopias, cerebellar hypoplasia, and inherited disorders of cognition such as familial mental retardation and familial autism; people with these conditions also often have epilepsy. The structural brain abnormalities are usually diagnosed by brain MRI or sometimes CT scans. Adults and children with these conditions, and their family members, are invited to participate in our study. By comparing the DNA of individuals or families that carry EDHC to the DNA of people in the general population, it may be possible to learn more about the genetic bases of certain forms of EDHC.

Study participants must have a brain malformation or disorder of cognition such as mental retardation or autism in addition to epilepsy to take part in this research.

Title:  Genetics of Charcot Marie Tooth (CMT) – Modifiers of CMT1A, New Causes of CMT2 (INC-6602)

Stage: Recruiting

Principal Investigator: Michael E. Shy, MD

University of Iowa

Iowa City, IA

This study includes two projects. One is looking for new genes that cause Charcot Marie Tooth disease (CMT). The other is looking for genes that do not cause CMT but may modify existing symptoms a person has.

This project aims to understand modifier genes and how they influence the severity of disease expression, along with identifying new forms of CMT that have not been genetically determined. Subjects eligible will either have CMT type 1A (CMT1A) or an unknown form of CMT. Blood will be drawn and sent to the University of Miami, where they receive the coded sample and process it through exome sequencing. Subjects will be told that this is optional.