Agenesis of the Corpus Callosum Health Article

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.