Schizencephaly

What Causes Schizencephaly?

In most cases, the precise cause of Schizencephaly is unknown. In some instances, the condition may be caused by abnormal changes (mutations) in specific genes, but more often, it seems to stem from an event or situation that affects the fetus during the early development of the brain.

Factors that appear to increase the risk of Schizencephaly include:

• Young age of the mother
• Use of certain medications, such as the blood thinner warfarin, during pregnancy
• Infections such as cytomegalovirus during pregnancy
• Complications of a prenatal amniocentesis procedure

Is Schizencephaly Hereditary?

Most cases of Schizencephaly are not inherited, and the affected child has no family history of the disorder. However, in a small number of cases, the condition has occurred in more than one family member. In addition, it has been associated with mutations in several genes, including the EMX2, SIX3, SHH, and COL4A1 genes. In these cases, the condition seems to have been inherited.

How Is Schizencephaly Detected?

Schizencephaly may be detected via ultrasound imaging exams after the twentieth week of pregnancy. If an ultrasound shows the possibility of clefts in the cerebral hemispheres at this point, doctors may order a magnetic resonance imaging (MRI) scan, which can more definitively identify the defect. Another MRI after birth may be used to confirm the diagnosis and determine the extent of the malformation.

How Is Schizencephaly Diagnosed?

The diagnostic process for Schizencephaly typically includes:

• Imaging scans such as magnetic resonance imaging (MRI) or computerized tomography (CT) to look for clefts and other brain abnormalities commonly associated with Schizencephaly
• Genetic testing to look for mutations associated with Schizencephaly may be recommended if the doctor suspects a genetic cause

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Schizencephaly Treated?

Schizencephaly has no cure. However, some treatments and therapies may lessen the impact of symptoms, improve quality of life and prevent complications. Common treatments and therapies include:

• Anti-seizure medications
• Physical therapy
• Occupational therapy
• Surgery to place a thin tube (called a shunt) in the brain to drain fluid when hydrocephalus is a complication

In some cases, where seizure activity was localized near the cleft, and the seizures did not respond to medication, surgery to remove the cleft has effectively controlled the seizures.

How Does Schizencephaly Progress?

The long-term outlook for people with Schizencephaly varies according to the severity and location of the clefts, as well as the presence of other associated brain abnormalities.

Potential long-term complications of Schizencephaly include:

• Speech or language impairments
• Epilepsy
• Paralysis on one or both sides of the body
• Intellectual disability
• Fluid accumulation in the brain (hydrocephalus) that may cause neurological symptoms

How Is Schizencephaly Prevented?

Avoidance of risk factors during pregnancy is the best way to decrease the risk of Schizencephaly:

• Get vaccinations as recommended by your doctor and take steps to avoid infections.
• Avoid medications that have been associated with Schizencephaly.
• Get good prenatal care to lessen the chance of pregnancy complications.

Parents with a family history of the disorder or who have had another child with familial Schizencephaly are advised to consult a genetic counselor to assess their risk if they plan to have another child.

Schizencephaly Caregiver Tips

• Be an advocate for your child. Learn all you can about schizencephaly so you can better understand the challenges your child faces, and be prepared to educate others about what they can do to help and support you and your child.
• Remember that you’re not alone. Connections with others who are going through the same thing can help. The Child Neurology Foundation maintains educational resources, access to one-to-one peer networks, and links to support groups.

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

• Schizencephaly has sometimes been associated with attention-deficit/hyperactivity disorder (ADHD).
• In some cases, schizencephaly has been associated with psychotic behavior.
• Schizencephaly may sometimes be associated with bipolar disorder.

Schizencephaly Brain Science

Mutations in the COL4A1 gene have been associated with Schizencephaly. This gene carries instructions for making one part of type IV collagen, a protein vital in creating membranes that help strengthen and hold together tissues throughout the body. Some scientists believe the COL4A1 mutations interfere with the normal production of type IV collagen, and, as a result, tissues are weaker than usual. Weakened tissue in the brain can break down when subjected to trauma such as inflammation from infections, and the abnormal development of clefts can result.

Schizencephaly Research

Title: Human Epilepsy Genetics–Neuronal Migration Disorders Study

Stage: Recruiting

Principal investigator: Christopher A. Walsh, MD, PhD  

Boston Children’s Hospital

Boston, MA

The purpose of this study is to identify genes responsible for epilepsy and disorders of human cognition.

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 we study include brain malformations, such as polymicrogyria, lissencephaly, Walker-Warburg syndrome, heterotopias and 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: HCRN Core Data Project: Characterizing Patient Populations in the Hydrocephalus Clinical Research Network (HCRN)

Stage: Recruiting

Contact: Curtis J. Rozzelle, MD

Children’s Hospital of Alabama

Birmingham, AL

The Hydrocephalus Clinical Research Network (HCRN) has been established by philanthropic funding to conduct multi-institutional research (clinical trials and observational studies) on pediatric hydrocephalus. In addition to philanthropic funding, the HCRN has also received an NIH NINDS Challenge Grant to support the network infrastructure, which allows for this and other network studies. The HCRN consists of multiple Clinical Centers and the Data Coordinating Center (DCC). The HCRN Core Data Project will obtain data about all neurosurgical hydrocephalus events from the network Clinical Centers and create a database to be used by HCRN investigators. The ongoing maintenance of the Core Data Project serves two primary purposes: 1) it will help investigators understand the variability, progression, and current treatment practices for hydrocephalus in children, with an ultimate goal of better guiding and assessing therapeutic intervention and providing recommendations on patient care and, 2) it will provide pilot and descriptive data necessary for hypothesis generation and study design (i.e., preliminary power analyses, recruitment projections) for studies under development by the HCRN. This multi-institutional database will be maintained throughout the lifetime of the HCRN and may be useful for tracking trends in pediatric hydrocephalus over time. The Core Data Project will be an invaluable resource to the HCRN and will help stimulate new research protocols, identify the potential need for future network expansion to incorporate additional patient populations, and provide a descriptive understanding of children with hydrocephalus cared for within the network.

Title: COL4A1 Gene-Related Cerebra-retinal Angiopathy (COL4A1)

Stage: Completed

Principal investigator: Hugues Chabriat, MD,PhD

Hôpital Lariboisiere Neurology Department

Paris, France

This prospective multicenter cohort study aims to define the clinical, radiological, and mutational spectrum of the disease related to the COL4A1 gene.

Clinical brain MRI-MRA and genetic testing (COL4A1 mutation screening) will be conducted for each included patient or asymptomatic relatives. Thirteen French investigating centers will participate in the study.