Corpus Callosum, Agenesis

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Corpus callosum, agenesis

Definition

Agenesis of the corpus callosum is the complete or partial absence of the corpus callosum, the structure within the brain that connects the two hemispheres.

Description

Agenesis of the corpus callosum is a congenital anomaly occurring during the first trimester of pregnancy. During this time, the fetal brain is developing, and bundles of nerve fibers that create the corpus callosum are forming. This process may be interrupted if the mother is exposed to toxic substances or certain medications during pregnancy. Genetic abnormalities in the fetus may prevent the nerve fibers from growing correctly. In most cases, the exact cause of agenesis of the corpus callosum is unknown.

In some people with agenesis of the corpus callosum, these nerve fibers are formed, but grow from front to back rather than from side to side. When the anomaly forms from front to back, groups of nerve fibers known as bundles of Probst form. These bundles stay within each hemisphere, never crossing the midline, and the two sides of the brain cannot share information. This lack of communication causes the symptoms of agenesis of corpus callosum.

The term agenesis of the corpus callosum usually refers to a complete absence of the corpus callosum. In some individuals, the corpus callosum is partially formed, and the condition is referred to as dysgenesis of the corpus callosum. There are two types of dysgenesis of the corpus callosum, partial and atypical. Partial dysgenesis occurs when the front, or anterior, portion of the corpus callosum does not form. In atypical dysgenesis of the corpus callosum, the rear, or posterior, portion the corpus callosum is not formed.

The corpus callosum is not essential for life or for normal intellectual functioning. Many people who have agenesis of the corpus callosum as an isolated condition have no symptoms at all, and some may only experience mild difficulties with skills that required matching visual patterns. Since the two hemispheres of the brain cannot communicate, images seen by one eye cannot be connected to images processed by the other.

The more severe symptoms experienced by people with agenesis of the corpus callosum are most often caused by other brain malformations, chromosomal abnormalities , and genetic syndromes of which agenesis of the corpus callosum is only one component. Especially in children who have agenesis of the corpus callosum in addition to other brain malformations, the effects can be severe, including mental retardation, seizures, hydrocephalus , and impairment of motor functioning.

Agenesis of the corpus callosum often occurs along with other brain malformations, such as Arnold-Chiari malformation , Dandy-Walker malformation , and other defects of the midbrain. It may also be found in patients with defects of the size and shape of the brain, such as schizencephaly lissencephaly , pachygyria, and hydrocephalus.

Individuals with anomalies of the formation of the forebrain, such as frontal encephalocele and holoprosencephaly , will usually have agenesis of the corpus callosum as well. In this case, the forebrain does not develop into two distinct hemispheres and the corpus callosum does not form. These are severe birth defects and are usually incompatible with life.

Agenesis of the corpus callosum may occur as an isolated birth defect; in such cases, a genetic cause has not been identified. However, it often occurs as part of a syndrome. Agenesis of the corpus callosum has been associated with more than 30 inherited syndromes caused by chromosomal and single-gene anomalies and may result from prenatal exposure to anticoagulant medication during the first trimester of pregnancy.

Agenesis of the corpus callosum may also be known as absent corpus callosum, corpus callosum hypoplasia, ACC, CCA, collasal agenesis, or collasal dysgenesis.

Genetic profile

Agenesis of the corpus callosum is a component of many different genetic syndromes and chromosomal abnormalities, most of which are extremely rare.

Examples of autosomal malformation syndromes that include agenesis of the corpus callosum are:

acrocallosal syndrome
Andermann syndrome
craniofacial dysmorphism-absent corpus callosumiris colobomas-connective tissue dysplasia syndrome
Fryns syndrome
Joubert syndrome
Larsen syndrome
Miller-Dieker syndrome
Rubinstein-Taybi syndrome
Seckel syndrome
Varadi-Papps syndrome

Agenesis of the corpus callosum is found in X-linked malformation syndromes such as:

Acardi syndrome
Berry-Kravis and Israel syndrome
Brooks syndrome
CRASH syndrome
Opitz-Kaveggia syndrome (FG syndrome)
Proud syndrome
Toriello-Carey syndrome
X-linked hydrocephalus

Agenesis of the corpus callosum occurs more frequently in individuals with trisomies, such as trisomy 3, trisomy 13 , trisomy 15, and trisomy 18 . It has also been associated with chromosomal rearrangements, such as Wolf-Hirschhorn syndrome (del(4)(p16)). It is also part of syndromes whose exact cause is still unknown, such as Bohring syndrome, congenital thrombocytopenia-Robin sequence-agenesis of corpus callosum-distinctive facies-developmental delay syndrome, Curry-Jones syndrome, Proteus syndrome , and agenesis of corpus callosum-mental retardation-osseous lesions syndrome.

Demographics

Researchers estimate the frequency of individuals affected with agenesis of the corpus callosum in the United States to be approximately 5.3%. It is more common in females than males and is often seen in individuals with other brain malformations and as a part of many complex chromosomal and genetic syndromes.

Signs and symptoms

The symptoms of agenesis of the corpus callosum can range from virtually no difficulties to significant delays in reaching developmental milestones, mental retardation, and limited mobility.

Agenesis of the corpus callosum may be asymptomatic if occurring as an isolated brain malformation. With the increased use of imaging studies, many cases of absence of the corpus callosum are inadvertently discovered when a patient has a test to diagnose an unrelated condition. For many people with agenesis of the corpus callosum, however, symptoms of other clinical and genetic syndromes and brain malformations can be severe, especially in infants.

Symptoms of agenesis of the corpus callosum may include:

seizures
delays in reaching developmental milestones, such as sitting up, crawling, and walking
mental retardation
poor hand-to-eye coordination
impairments in auditory and visual memory

Although agenesis of the corpus callosum can be asymptomatic, it is considered a risk factor for neurological impairment. Agenesis of the corpus callosum may be suspected in children who have seizures, especially a specific type of seizures called infantile spasms. Agenesis of the corpus callosum may also be suspected in children with feeding problems, poor muscle control, and difficulties sitting, standing, and walking. It may be diagnosed later in children who experience other symptoms, such as frequent headaches or repetitive speech, in addition to seizures.

Diagnosis

Agenesis of the corpus callosum is diagnosed primarily by computed tomography (CT) scan and magnetic resonance imaging (MRI). MRI is the preferred imaging method for identifying abnormalities of the structures of the brain.

Agenesis of the corpus callosum may be diagnosed prenatal after week 20 of gestation, using prenatal ultrasound .

Treatment and management

There is no treatment for agenesis of the corpus callosum; however, the symptoms may be managed. Most symptoms associated with agenesis of the corpus callosum are caused by other anomalies that occur along with the defect.

Symptoms, such as seizures, may be treated with anticonvulsant medications. Another common associated condition, hydrocephalus, may be treated by the surgical installation of a medical device called a shunt. A shunt relieves the pressure of access fluid in the brain by draining that fluid away from the brain.

For infants and young children with agenesis of the corpus callosum and syndromes that include agenesis of the corpus callosum, early intervention programs may be helpful in assisting these children to reach developmental milestones. Other treatments, such as occupational therapy, physical therapy, and speech therapy, may help individuals improve deficits caused by the accompanying malformations.

Prognosis

The prognosis for individuals with agenesis of the corpus callosum varies widely. If agenesis of the corpus callosum occurs alone, the prognosis is usually excellent. Depending on the other associated birth defects and the severity of the syndrome affecting the patient, mental retardation, impaired neuromuscular functioning, and a shortened life expectancy may result. In rare cases, syndromes that may include agenesis of the corpus callosum are incompatible with life.

Resources

PERIODICALS

Shevell, Michael. "Clinical and Diagnostic Profile of Agenesis the Corpus Callosum." Journal of Child Neurology 17, no 12 (December 2002): 895–899.

ORGANIZATIONS

March of Dimes. 1275 Mamaroneck Ave., White Plaines, NY 10605. (April 9, 2005.) <http://www.marchofdimes.com>.

National Organization of Disorders of the Corpus Callosum. 18032-C Lemon Drive, PMB 363, Yorba Linda, CA 92886. (April 9, 2005.) <http://www.corpuscallosum.org>.