Schizencephaly

Title

Other Names:

Familial schizencephaly

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

Schizencephaly is a rare congenital (present from birth) brain malformation in which abnormal slits or clefts form in the cerebral hemispheres of the brain. The signs and symptoms of this condition may include developmental delay, seizures, and problems with brain-spinal cord communication. Affected people may also have an abnormally small head (microcephaly); hydrocephalus; intellectual disability; partial or complete paralysis; and/or poor muscle tone (hypotonia).^[1] Severity of symptoms depends on many factors including the extent of the clefting and whether or not other brain abnormalities are present.^[2] Although the exact cause of schizencephaly is unknown, it has been linked to a variety of genetic and non-genetic factors.^[2]^[3] Treatment generally consists of physical therapy and drugs to prevent seizures. In cases that are complicated by hydrocephalus, a surgically implanted tube, called a shunt, is often used to divert fluid to another area of the body where it can be absorbed.^[1]

Last updated: 11/17/2014

Symptoms Symptoms

Signs and symptoms of schizencephaly may include:^[1]^[2]

Developmental delay
Seizures
Abnormally small head (microcephaly)
Intellectual disability
Partial or complete paralysis
Poor muscle tone (hypotonia)
Hydrocephalus

Severity of symptoms depends on many factors, including the extent of the clefting and whether or not other brain abnormalities are present. For example, people with a small cleft in one hemisphere may have paralysis on one side of the body and little to no intellectual disability, while clefts in both hemispheres can lead to quadriplegia (paralysis of both arms and legs) and severe intellectual disability.^[2]

Last updated: 11/18/2014

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Aplasia/Hypoplasia of the corpus callosum	90%
EEG abnormality	90%
Hypertonia	90%
Porencephaly	90%
Strabismus	90%
Cognitive impairment	50%
Hemiplegia/hemiparesis	50%
Seizures	50%
Schizencephaly	-

Last updated: 9/1/2016

Cause Cause

The exact cause of schizencephaly is unknown.^[4] A small number of people with schizencephaly are found to have changes (mutations) in one of four genes: EMX2, SIX3, SHH, and COL4A1.^[5]^[3]^[6] Rarely, schizencephaly can affect more than one family member.^[4]^[7]^[8]^[9] This supports a genetic cause in some cases.^[4]

Schizencephaly has also been linked to a variety of non-genetic factors, including young maternal age and certain medications and infections that can cause vascular disruptions (disruption of blood flow or blood supply) in a developing baby.^[2]

Last updated: 11/18/2014

Inheritance Inheritance

Schizencephaly is not thought to be inherited in most cases and it rarely affects more than one person in a family.^[4]^[7]^[8] A few cases of familial schizencephaly have been linked to changes (mutations) in the EMX2 gene.^[10]

Last updated: 11/22/2014

Diagnosis Diagnosis

In rare cases, people affected by schizencephaly are found to have changes (mutations) in one of four genes: EMX2, SIX3, SHH, and COL4A1.^[3] Genetic testing is available for these families.^[11]

Last updated: 11/18/2014

Schizencephaly is typically diagnosed by computed tomography (CT) and/or magnetic resonance imaging (MRI).^[2] A CT scan is an imaging method that uses x-rays to create pictures of cross-sections of the body, while an MRI scan uses powerful magnets and radio waves to create pictures of the brain and surrounding nerve tissues. Both of these imaging methods can be used to identify brain abnormalities such as the slits or clefts found in people with schizencephaly.

In some cases, schizencephaly can also be diagnosed prenatally (before birth) on ultrasound after 20 weeks gestation. If clefting is seen on ultrasound, an MRI scan of the developing baby may be recommended to confirm the diagnosis.^[2]^[12]

Last updated: 11/18/2014

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

The best treatment options for people with schizencephaly depend on many factors, including the severity of the condition and the signs and symptoms present. For example, people with developmental delay (i.e. delayed motor milestones) or partial paralysis may be referred for physical therapy and/or occupational therapy. Medications are often prescribed to prevent seizures. In cases that are complicated by hydrocephalus, a surgically implanted tube, called a shunt, is often used to divert fluid to another area of the body where it can be absorbed.^[1]^[2]

Last updated: 11/18/2014

Prognosis Prognosis

The long-term outlook for people with schizencephaly varies depending on the size and location of the clefts and the extent of intellectual disabilities.^[1]^[2] For example, children with a small cleft in one hemisphere may have paralysis on one side of the body and little to no intellectual disability, while clefts in both hemispheres can lead to quadriplegia (paralysis of both arms and legs) and severe intellectual disability.^[2]

Last updated: 11/18/2014

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The Christopher A. Walsh Laboratory is interested in the development of the cerebral cortex. Abnormal development of the cerebral cortex in humans results in epilepsy, autism, mental retardation, dyslexia, and other learning disorders, and perhaps some psychiatric conditions as well. Several of their projects are directed at trying to understand the basic biology of the cortex by studying the mutations that disturb its development. Conditions that they are currently researching include: double cortex syndrome, periventricular heterotopia, schizencephaly, perisylvian polymicrogyria and Walker Warburg syndrome. Click on the link above to access further information about this research.
ClinicalTrials.gov lists trials that are studying or have studied Schizencephaly. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.
The Cortical Foundation provides information on participating in research for cortical malformations of the brain.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Epilepsy Society
135 South LaSalle Street
Suite 2850
Chicago, IL 60603
Telephone: +1-312-883-3800
Fax: +1-312-896-5784
E-mail: info@aesnet.org
Website: https://www.aesnet.org/
Birth Defect Research for Children, Inc.
976 Lake Baldwin Lane, Suite 104
Orlando, FL 32814
Telephone: 407-895-0802
E-mail: staff@birthdefects.org
Website: http://www.birthdefects.org/
Brain Foundation
P O Box 579
Crows Nest, NSW
1585 Suite 21
Regent House 37-43
Alexander Street Crows Nest, NSW 2065
Australia
Telephone: 61 2 9437 5967
Fax: 61 2 9437 5978
E-mail: http://brainfoundation.org.au/contact
Website: http://www.brainfoundation.org.au/
Cortical Foundation
PO Box 340894
Austin, TX 78734
Telephone: +1 (512) 256-3855
E-mail: info@cortfoundation.org
Website: http://cortfoundation.org/cms/
Epilepsy Foundation
8301 Professional Place East
Suite 200
Landover, MD 20785-2238
Toll-free: 800-EFA-1000 (800-332-1000)
Telephone: 301-459-3700
Fax: 301-577-4941
E-mail: info@efa.org
Website: http://www.epilepsyfoundation.org
Schiz Kidz Buddies Online Support Group for Schizencephaly
Website: http://www.schizkidzbuddies.com/
The Arc of the United States
1010 Wayne Avenue, Suite 650
Silver Spring, MD 20910
Toll-free: (800) 433-5255
Telephone: (301) 565-3842
Fax: (301) 565-3843 or (301) 565-5342
E-mail: info@thearc.org
Website: http://www.thearc.org
We Are R.A.R.E.
4208 Chateau Road
Orlando, FL 32808
Telephone: (407) 617-4111
E-mail: contact-us@wearerare.org
Website: http://www.wearerare.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

MedlinePlus provides more information on head and brain malformations. MedlinePlus is a Web site designed by the National Library of Medicine to help you research your health questions.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Schizencephaly. Click on the link to view a sample search on this topic.

News & Events News & Events

NCATS Co-Sponsored Conferences

David W. Smith Workshop on Malformations and Morphogenesis Friday, September 9, 2011 - Wednesday, September 14, 2011
Location: UCLA Lake Arrowhead Conference Center, Lake Arrowhead , CA
Description: Themes for 2011; Mechanisms of normal and abnormal morphogenesis including insights from prenatal imaging; Somatic overgrowth; Brain overgrowth; Cortical dysplasia; Signaling pathways in morphogenesis; Angiogenesis and vascular malformations in genetic syndromes

Contact: Mary Lou Oster-Granite, Ph.D.(301) 435-6866mo96o@nih.gov

Co-funding Institute(s): National Institute of Child Health and Human Development, Office of Rare Diseases Research
- Agenda ( - 50KB)

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

What causes this to happen? See answer
How many cases of schizencephaly have been reported in Florida, and worldwide? Will my child always have develomental delay, and will this get worse with every seizure? What is the prognosis for this condition? See answer

Have a question? Contact a GARD Information Specialist.

References References

NINDS Schizencephaly Information Page. National Institute of Neurological Disorders and Stroke. April 16, 2014; http://www.ninds.nih.gov/disorders/schizencephaly/schizencephaly.htm. Accessed 11/17/2014.
Schizencephaly. Orphanet. May 2014; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=799. Accessed 11/17/2014.
Schizencephaly. OMIM. May 2014; http://omim.org/entry/269160. Accessed 11/17/2014.
Hilburger AC, Willis JK, Bouldin E, Henderson-Tilton A. Familial schizencephaly. Brain & Development. May-June 1993; 15(3):234-236. http://www.ncbi.nlm.nih.gov/pubmed/8214352. Accessed 4/28/2011.
Yoneda et al. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Ann. Neurol. 2013; 73:48-57. Accessed 11/18/2014.
Hehr U et al. Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly. Human Genetics. March 2010; 127(5):555-561. http://www.ncbi.nlm.nih.gov/pubmed/20157829. Accessed 4/28/2011.
Hosley, M. A., Abroms, I. F., Ragland, R. L. Schizencephaly: case report of familial incidence. Pediat. Neurol. 1992; 8:148-150. Accessed 11/18/2014.
Robinson, R. O. Familial schizencephaly. Dev. Med. Child Neurol. 1991; 33:1010-1014. Accessed 11/18/2014.
Tietjen I, Erdogan F, Currier S, Apse K, Chang BS, Hill RS, Lee CK, Walsh CA. EMX2-independent familial schizencephaly: clinical and genetic analyses. Am J Med Genet A. June 2005; 135(2):166-170. Accessed 11/18/2014.
Faiella, A., Brunelli, S., Granata, T., D'Incerti, L., Cardini, R., Lenti, C., Battaglia, G., Boncinelli, E. A number of schizencephaly patients including 2 brothers are heterozygous for germline mutations in the homeobox gene EMX2. Europ. J. Hum. Genet. 1997; 5:186-190.
Schizencephaly. Genetic Testing Registry. http://www.ncbi.nlm.nih.gov/gtr/conditions/C0266484/. Accessed 11/18/2014.
Ken R Close, MD. Schizencephaly Imaging. Medscape. November 2013; http://emedicine.medscape.com/article/413051-overview. Accessed 11/18/2014.