Project Description

Agenesis of the Corpus Callosum Fast Facts

Agenesis of the corpus callosum (ACC) is a disorder in which the structure that normally connects the two sides of the brain fails to develop during pregnancy.

ACC can be caused by several factors, including an infection during pregnancy, genetics, or fetal alcohol syndrome.

ACC is present at birth. The corpus callosum may be entirely absent, or it may be underdeveloped.

The symptoms of ACC vary widely. In some cases, no symptoms are present at birth but may develop later. In mild cases, there may be no visible symptoms at all.

ACC is present at birth. The corpus callosum may be entirely absent, or it may be underdeveloped.

What is Agenesis of the Corpus Callosum?

Agenesis of the corpus callosum (ACC) is a brain disorder in which the structure that connects the two sides of the brain, the corpus callosum, is either partially or entirely missing. The condition develops during pregnancy and is present at birth.

The corpus callosum facilitates communication between the left and right cerebral hemispheres of the brain. When it is absent, normal communication between the two halves of the brain is not possible. Neurological and developmental symptoms can result. However, in some cases, the condition’s effects are mild and may go completely unnoticed.

Symptoms of ACC

ACC symptoms are often not noticeable at birth but may become more apparent as the child gets older. The effects of the disorder may have a more significant impact later in childhood. In cases where there are no other neurological abnormalities, ACC symptoms often do not cause serious complications.

Common symptoms of ACC include:

  • Feeding and swallowing difficulties
  • Sleep disruptions
  • Weak muscle tone
  • Coordination problems
  • Seizures
  • Accumulation of fluid around the brain (hydrocephalus)
  • Delays in motor skills such as sitting, crawling, or walking
  • Delays in language development
  • Impaired vision
  • Impaired hearing
  • Intellectual impairment
  • Behavioral disorders such as attention-deficit/hyperactivity disorder (ADHD)
  • Learning disabilities

What Causes Agenesis of the Corpus Callosum?

ACC has many different possible causes, and it is usually not apparent what triggered the condition’s development during pregnancy.

Factors associated with ACC include:

  • Genetics
  • Viral infections during pregnancy
  • Exposure to alcohol during pregnancy (fetal alcohol syndrome)
  • Exposure to toxins during pregnancy
  • Brain cysts

ACC often occurs in conjunction with other syndromes and brain abnormalities, including:

  • Arnold-Chiari malformation
  • Dandy-Walker syndrome
  • Schizencephaly (abnormal divisions in the brain)
  • Holoprosencephaly (lack of normal separation of the brain’s hemispheres)
  • Aicardi syndrome

Is Agenesis of the Corpus Callosum Hereditary?

In some cases, ACC  may be inherited in either an autosomal recessive or X-linked dominant pattern.

An autosomal recessive disorder only develops if a child inherits two copies of the disease-causing genetic mutation, one from each parent. Parents who have only one copy of the mutation do not develop the disorder, but they may pass the mutation on to their children. Two parents who carry the ACC-causing mutation have a 25 percent chance of having a child with the disorder with each pregnancy.

In an X-linked dominant pattern, the disease-causing mutation is on the X chromosome, and only one copy of the mutation is necessary to cause the disorder. Females have two X chromosomes and will develop the condition if one of the chromosomes carries the mutation. Males have only one X-chromosome and develop a more severe form of the disorder if their X chromosome carries the mutation. Often, the condition is fatal to males during pregnancy. The result is that this form of the condition is more common in females. This is the case with ACC associated with Aicardi syndrome.

How Is Agenesis of the Corpus Callosum Detected?

Management of ACC symptoms is likely to be more effective when intervention starts early. Early diagnosis is challenging because symptoms are often overlooked through early childhood.

Sometimes, signs of ACC are apparent in ultrasound exams during pregnancy. However, the condition often goes unnoticed until some time after birth. Seizures are the most common symptom that will lead a doctor to suspect ACC in an infant or young child, but not all children with ACC experience seizures.

Other early signs of ACC can include:

  • Feeding difficulties
  • Problems holding the head upright
  • Delays in motor skills such as sitting, crawling, or walking
  • Other cognitive, intellectual, or motor delays
  • Accumulation of fluid around the brain (hydrocephalus)

How Is Agenesis of the Corpus Callosum Diagnosed?

A doctor may suspect ACC if a child presents symptoms of the disorder with no other apparent cause, especially if there are risk factors such as a family history of ACC. Doctors may also recommend diagnostic testing if they observe signs of ACC in routine ultrasound exams during pregnancy.

Diagnostic steps may include:

  • High-resolution ultrasound exams that provide more detail than routine ultrasound
  • Magnetic resonance imaging (MRI) either during pregnancy or after birth to confirm ACC and look for other abnormalities
  • Genetic testing during pregnancy via amniocentesis

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Agenesis of the Corpus Callosum Treated?

ACC has no cure, and there is no way to correct the absence of the corpus callosum. Treatments for the disorder focus on controlling symptoms. Various therapies can help people with the disorder lessen the impact of its complications. In mild cases that produce no significant symptoms, no treatment may be necessary.

Treatment for ACC may include:

  • Anti-seizure medications
  • Physical therapy
  • Speech therapy
  • Occupational therapy
  • Surgery to control hydrocephalus

How Does Agenesis of the Corpus Callosum Progress?

ACC is not a progressive disorder. The structural brain abnormalities characteristic of ACC don’t worsen over time. However, some symptoms and complications of the condition may not emerge until later in childhood.

Possible long-term complications of ACC include:

  • Seizures
  • Speech difficulties
  • Intellectual impairment
  • Headaches
  • Poor coordination
  • Impaired vision
  • Impaired hearing

How Is Agenesis of the Corpus Callosum Prevented?

In most cases, the cause of ACC is unclear, making it difficult to take steps to prevent the condition. People who have a family history of the disorder may want to seek the advice of a genetic counselor if they are planning to have children.

Risk factors to avoid include:

  • Excessive alcohol consumption during pregnancy
  • Exposure to drugs and toxins during pregnancy
  • Viral infections during pregnancy

Agenesis of the Corpus Callosum Caregiver Tips

  • Understand how ACC affects your child. Studies have shown that children with ACC are at increased risk of behavioral problems, social difficulties, and psychosocial disorders such as autism. When you learn about the neurological cause that underlies these complications, you may be more able to help your child live with the condition.
  • Don’t hesitate to reach out for the support you need. The Child Neurology Foundation provides access to a peer support network to assist families living with neurological disorders such as ACC.  

Agenesis of the Corpus Callosum Brain Science

The corpus callosum is comprised of nerve fibers that span the divide between the left and right hemispheres of the brain’s cerebral cortex. The function of the corpus callosum is to transmit nerve signals from one hemisphere to the other. This function comes into play when, for example, sensory input is delivered to one hemisphere and then is passed to the other hemisphere for processing. When the corpus callosum is absent, this kind of cross-hemisphere processing is not possible.

Scientists have discovered that many brain functions work just fine even without communication between the cerebral hemispheres. This may explain why some people with ACC experience mild symptoms or none at all. However, some functions, such as language processing, rely on collaboration between the hemispheres. For example, studies of people without a functional corpus callosum found that when they were shown an object visible to them only through their left eye, they could not think of the object’s name. The researchers hypothesized that the right cerebral hemisphere received the sensory input from the left eye as it normally does. But the sensory data couldn’t be sent to the left hemisphere, where the brain’s language-processing center is located.

Agenesis of the Corpus Callosum Research

Title:  Brain Development Research Program

Stage: Not yet 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 goal of the investigators’ research is to use a better understanding of the underlying genetic causes as a foundation to develop better treatments for these groups of patients.

“We are studying both the genetics and clinical features of these disorders. We hope to understand the problems faced by individuals with these disorders as well as their causes. In the future, we hope to develop therapies that are geared specifically for individuals based on the underlying biology. To participate in the study, you 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 from the parents. Please see contact information and our webpage below.”

 

Title: Study of Selected X-Linked Disorders: Aicardi Syndrome

Stage: Recruiting

Principal investigator: Ignatia B. Van den Veyver, MD

Baylor College of Medicine

Houston, TX

Aicardi syndrome is a sporadic X-linked dominant, presumably male-lethal, neurodevelopmental disorder. It was initially characterized by agenesis of the corpus callosum, neuronal migration defects, eye abnormalities (chorioretinal lacunae, colobomas of the optic nerve, and microphthalmia), and severe early-onset seizures and neurodevelopmental delay. It is now well recognized that other brain abnormalities, such as polymicrogyria, agyria, cysts, and heterotopias, are common features of Aicardi syndrome. It was previously hypothesized that the gene causing Aicardi syndrome and possibly other phenotypically similar disorders with X-linked inheritance, such as Goltz syndrome or Focal Dermal Hypoplasia, are in or near the region on chromosome Xp22 that is deleted in another condition named microphthalmia with linear skin defects syndrome (MLS) because all three have some clinical similarities. However, interim studies have shown that this is likely not the case because no mutations were found in Aicardi syndrome in human holocytochrome c-type synthetase (HCCS), the gene that is deleted or mutated in MLS. In addition, a mouse model for MLS has no features of Aicardi syndrome. Furthermore, mutations were identified in PORCN (Xp11.3) in Goltz syndrome patients, but not in Aicardi syndrome patients. Therefore, it is likely that the mutated gene is elsewhere on the X-chromosome.

For this study, information on patients is being collected with clinical findings suggesting a diagnosis of Aicardi syndrome, MLS syndrome, or a condition that phenotypically overlaps with these disorders. Detailed family history will be obtained when indicated, and additional family members will be evaluated after appropriately obtained written voluntary consent. A detailed report of the history or physical findings will be obtained from referring physicians for patients identified at outside facilities, or the participants may be evaluated by the study collaborators. Blood and skin biopsy will be obtained from affected individuals, unaffected parents, and from other affected or unaffected family members where indicated. It is anticipated that some severely affected patients will expire; in that case, (post mortem) pathological specimens may be obtained. Occasionally, affected individuals may undergo surgical procedures with the removal of tissues; in this case, we may obtain tissues that would be otherwise discarded or essential for further diagnostic studies or clinical care of the patient. It is anticipated that these specimens will be extremely valuable for understanding the pathogenesis of the investigated conditions. DNA, RNA, or protein will be prepared from leukocytes and from tissues and used for mutation analysis and other molecular studies of the identified genes. Permanent lymphoblastoid cell lines will be prepared and stored in the laboratory as a permanent source of DNA for the molecular studies.

 

Title: Human Epilepsy Genetics–Neuronal Migration Disorders Study

Stage: Recruiting

Contact: 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 human genome structure makes it a realistic goal to identify genes responsible for several other epileptic conditions.

The purpose of this study is 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 we study include brain malformations, such as polymicrogyria, lissencephaly, Walker-Warburg syndrome, heterotopias, cerebellar hypoplasia, and inherited disorders of cognition 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 in order to take part in this research.

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