Agenesis of the corpus callosum

Definition

Agenesis of the corpus callosum (ACC) is an abnormality of brain structure, present at birth, that is characterized by partial or complete absence of the corpus callosum. The corpus callosum is a bundle of nerve fibers that connects the two hemispheres (halves) of the brain and allows information to pass back and forth between both sides.

Description

Agenesis of the corpus callosum is one form of abnormal corpus callosum development. Other corpus callosum disorders include hypoplastic (thin or underdeveloped) corpus callosum and dysgenesis (abnormal formation) of the corpus callosum. In complete ACC, the corpus callosum is entirely missing. In partial ACC, some portion, usually the posterior portion, is absent. Agenesis of the corpus callosum is often found in combination with other brain abnormalities and some degree of mental impairment. Birth defects involving other parts of the body (especially the eyes, face, heart, and skeletal system) may also be present. ACC can occur alone, without other obvious brain abnormalities. In some of these cases, the affected person is healthy and has an IQ (intelligence quotient) in the normal range. Even in these cases however, subtle neuropsychological and cognitive abnormalities may exist.

Demographics

Estimates of the frequency of ACC range between 0.0005% and 0.7% of children. An incidence of 2–3% has been reported in children with developmental disabilities. Between one-half to three-quarters of cases of ACC occur in males. ACC is a feature of Aicardi syndrome, an X-linked (caused by a gene on the X chromosome) condition that occurs almost exclusively in females and is thought to be lethal in males.

Causes and symptoms

The corpus callosum forms during the fifth to sixteenth week of pregnancy. It is thought that ACC occurs when one or more factors interfere with the migration (movement) of cells in the brain that eventually form the corpus callosum. An underlying cause for ACC is found in about one-half of cases. Factors that may affect normal corpus callosum development include:

• prenatal infections, viruses, or toxic exposures such as rubella or fetal alcohol syndrome
• chromosome abnormalities such as trisomy 8, trisomy 13, and trisomy 18
• genetic syndromes such as Aicardi syndrome, acrocallosal syndrome, Andermann syndrome, Shapiro syndrome, and Menkes disease
• blocked growth of the corpus callosum due to cysts or other abnormal structures
• a cerebral dysgenesis syndrome, in which there is abnormal formation of the brain such as Dandy-Walker syndrome , Arnold-Chiari malformation , holoprosencephaly , or hydrocephalus

The symptoms of ACC largely depend on the presence or absence of other medical conditions. The majority of children with ACC with other brain abnormalities usually show signs of a neurological disorder by age two. Symptoms in these children can include:

• seizures
• developmental delay or mental retardation
• increased or decreased head size
• hydrocephalus (abnormal accumulation of cerebrospinalfluid in the spaces of the brain)
• cerebral palsy
• hypotonia (decreased muscle tone)
• failure to thrive

In children with ACC who otherwise have limited neurological problems, there are slight differences in cognition (thought processes) and psychosocial functioning compared with children without ACC. Neuropsychological testing has shown that such individuals can have any of the following:

• motor, language, or cognitive delays
• poor motor coordination
• sensitivity to tactile sensations
• high pain tolerance
• cognitive and social challenges

Cognitive and social challenges may become more apparent with age. Examples of these challenges include difficulties using language in social settings and with performing tasks that require complex reasoning, creativity, or problem-solving skills. Patients with ACC may display limited insight into one's own behavior, a lack of awareness of others' feelings, misunderstanding of social cues, limited sophistication of humor, and difficulty imagining consequences of behavior.

Diagnosis

A health professional suspicious of ACC may recommend a neurological evaluation that includes imaging studies. The more subtle cognitive and psychosocial problems found in individuals with isolated ACC are less likely to lead to the diagnosis. In some cases, the diagnosis of ACC is incidental, made in the course of an evaluation for other reasons. There may well be many asymptomatic individuals with partial or complete agenesis who never come to medical attention.

Diagnosis of ACC relies on imaging studies such as ultrasound (prenatal or postnatal), magnetic resonance imaging (MRI) , or computerized axial tomography (CT or CAT) scan. Diagnostic findings include:

• absence of the corpus callosum
• widely displaced and parallel lateral ventricles
• selective dilatation of the posterior horns
• widely spaced frontal horns
• upward displacement and enlargement of the third ventricle
• displaced orientation of gyral markings

Fetal ultrasound can detect some but not all cases of ACC, beginning at about 20 weeks of pregnancy. The prenatal or postnatal diagnosis of ACC should be followed by studies aimed to determine the cause for the ACC. Such studies may include chromosome analysis, metabolic screening, and genetic and ophthalmologic consultations.

Treatment team

Treatment for patients with ACC is highly individualized because the severity of symptoms varies from patient to patient. Depending upon the symptoms, many medical specialists can assist the patient's primary physician or nurse practitioner, including a neurologist , ophthalmologist, geneticist, neuropsychologist , behavioral psychologist, occupational therapist, physical therapist, speech-language pathologist, and experts in special education and early intervention.

Treatment

There is no cure for ACC. Treatment primarily includes management of associated problems such as seizures, hydrocephalus, and cerebral palsy.

Recovery and rehabilitation

Limited information is available about the optimal remedial strategies for individuals with ACC. Speech therapy, occupational therapy, physical therapy, and early intervention are common services provided to patients with ACC. The goal of these therapies is to maximize the patient's success in school, work, and life in general. Speech therapy can help patients with speech delays, apraxia (the inability to make voluntary movements despite normal muscle function), and difficulties with pragmatics or social language use. Occupational therapy can help patients with sensory integration problems. Physical therapy can help address problems such as impaired coordination, motor delays, and spasticity (abnormally increased muscle stiffness and restricted movement).

Clinical trials

There are currently no clinical trials for patients with agenesis of the corpus callosum. Patients and families may elect to participate in genetic research. Laboratories searching for genes associated with agenesis of the corpus callosum include the laboratory of Elliott H. Sherr M.D., Ph.D, at the University of California, San Francisco, and the Harvard Institutes of Medicine. Both labs accept contact from patients and families.

Prognosis

The prognosis for ACC varies according to the presence and severity of associated problems such as microcephaly (small head), seizures, cerebral palsy, and cerebral dysgenesis. In the case of a fetus diagnosed with isolated ACC, prediction of outcome remains imprecise. Estimates of the chance for a normal developmental outcome for a case detected prenatally range from 35–85%. It has also been stated that a so-called "normal" or "asymptomatic" outcome for ACC does not exist. Subtle or cognitive and psychosocial differences have been found in patients with ACC and a normal IQ.

Special concerns

The special educational needs of children with ACC vary. Children with ACC may be eligible for an individual education plan (IEP). An IEP provides a framework from which administrators, teachers, and parents can meet the educational needs of a child with ACC. Depending upon severity of symptoms and the degree of learning difficulties, some children with ACC may be best served by special education classes or a private educational setting.

Resources

BOOKS

Brown, W. S., and M. T. Banich, eds. Development of the Corpus Callosum and Interhemispheric Interactions: A Special Issue of Developmental Neuropsychology. Mahwah, NJ: Lawrence Erlbaum Associates, Inc., 2001.

Lassonde, M., and M. Jeeves, ed. Callosal Agenesis: A Natural Split Brain? New York: Plenum Press, 1994.

Parker, James N., and Philip M. Parker, eds. The Official Parent's Sourcebook on Agenesis of the Corpus Callosum: A Revised and Updated Directory for the Internet Age. San Diego: ICON Health Publications, 2002.

Rourke, B. P., ed. Syndrome of Nonverbal Learning Disabilities: Neurodevelopmental Manifestations. New York: Guilford Press, 1995.

PERIODICALS

Brown, W. S., and L. K. Paul. "Cognitive and Psychosocial Deficits in Agenesis of the Corpus Callosum with Normal Intelligence." Cognitive Neuropsychiatry 5 (2000): 135–157.

Davila-Gutierrez, G. "Agenesis and Dysgenesis of the Corpus Callosum." Seminars in Pediatric Neurology 9 (December 2002): 292–301.

Goodyear, P. W., C. M. Bannister, S. Russell, and S. Rimmer. "Outcome in Prenatally Diagnosed Fetal Agenesis of the Corpus Callosum." Fetal Diagnosis and Therapy 16 (May–June 2001): 139–145.

Shevell, M. I. "Clinical and Diagnostic Profile of Agenesis of the Corpus Callosum." Journal of Child Neurology 17 (December 2002): 896–900.

Stickles, J. L., G. L. Schilmoeller, and K. J. Schilmoeller. "A 23-Year Review of Communication Development in an Individual with Agenesis of the Corpus Callosum." International Journal of Disability, Development and Education 49 (2002): 367–383.

WEBSITES

The National Institute of Neurological Disorders and Stroke (NINDS). Agenesis of the Corpus Callosum Information Page. (March 30, 2004.) <http://www.ninds.nih.gov/health_and_medical/disorders/agenesis_doc.htm>.

Corpal Home Page. (March 30, 2004.) <http://www.corpal.org.uk/>.

National Center for Biotechnology Information. Online Mendelian Inheritance in Man (OMIM) Home Page. (March 30, 2004.) <http://www.ncbi.nlm.nih.gov/omim/>.

ORGANIZATIONS

Agenesis of the Corpus Callosum (ACC) Network, 5749 Merrill Hall, Room 118, University of Maine, Orono, ME 04469-5749. (207) 581-3119; Fax: (207) 581-3120. UMACC@maine.edu.

Aicardi Syndrome Foundation. P.O. Box 3202, St. Charles, IA 60174. (800) 374-8518. [email protected]. <http://www.aicardisyndrome.org>.

National Organization for Disorders of the Corpus Callosum (NODCC). 18032-C Lemon Drive PMB 363, Yorba Linda, CA 92886. (714) 717-0063. <http://www.corpuscallosum.org>.

Dawn J. Cardeiro, MS, CGC