What Is Agenesis of the Corpus Callosum?
The corpus callosum — a collection of many millions of nerve fibers in the middle of the brain — is the largest connection between the two sides of the brain, or hemispheres. The corpus callosum coordinates signals between the hemispheres and helps us integrate and synthesize information in a complete way.
Agenesis (absence) of the corpus callosum is a condition in which this structure is either partially or completely missing. It is the most common congenital brain abnormality and may be present in 1 per 4,000 live births. Agenesis of the corpus callosum may occur as an isolated brain problem or in association with other abnormalities of the brain or of other organs such as the heart.
What Causes Agenesis of the Corpus Callosum?
The corpus callosum develops from front to back starting at eight weeks of gestation and continuing through 20 weeks when the final shape is complete. However, the maturation of the corpus callosum continues after birth.
The formation of the corpus callosum involves complex interactions between a variety of cell types in the fetal brain. This multi-step process coordinates the development and movement of these cells and the arrangement and growth of nerve fibers. Alterations in any of these steps may result in abnormal development of the corpus callosum.
In most cases, it is not possible to know what specifically caused the disruption. In 30 to 45 percent of cases, there is an associated genetic condition. Approximately one-third of these genetic conditions are due to mutation in a single gene. They may also be related to a mixture of genetic and acquired factors (infectious, vascular or toxic). In most cases, this condition is not inherited, but rather a new occurrence at the time of conception. Prenatal testing may help determine whether there is a genetic or infectious cause such as cytomegalovirus, toxoplasmosis, rubella or influenza. In most cases, prenatal testing requires an amniocentesis.
How Is Agenesis of the Corpus Callosum Diagnosed?
In practice, it can be difficult to diagnose the presence or absence of the corpus callosum on routine fetal ultrasounds. However, other brain structures are easier to detect and can provide indirect evidence of corpus callosum development. One such structure, the cavum septum pellucidum (CSP), is formed in the seventh or eighth week of gestation, around the same time that the corpus callosum starts to develop. If the CSP is absent or not well visualized after week 18 of gestation, an abnormal corpus callosum is suspected and a fetal MRI may be recommended.
A fetal MRI can diagnose this condition as early as 18 weeks of gestation and determine if other structures in the fetal brain are developing normally. An accurate prenatal diagnosis may lead to counseling and care changes before or after delivery, as well as provide additional information for other anatomical abnormalities not seen on fetal ultrasound. When diagnosed, abnormalities of the corpus callosum may be described as a partial or complete agenesis, dysplastic (abnormally formed) or hypoplastic (thin) corpus callosum. Some abnormalities may not be detected by the fetal MRI and may only be detected after imaging or examination of the newborn baby.
How Is Agenesis of the Corpus Callosum Treated?
The management of fetuses with suspicion for corpus callosum abnormalities starts prenatally. Most pregnant mothers referred to The Chicago Institute for Fetal Health will have a fetal MRI to visualize the corpus callosum abnormality and evaluate for other brain abnormalities. However, there is no specific prenatal treatment for agenesis of the corpus callosum.
Once the diagnosis is confirmed, the mother is followed with serial ultrasounds every four to six weeks for the remainder of the pregnancy to make sure that the baby is growing and thriving. The baby will be delivered vaginally unless there is some other reason for a cesarean delivery. After delivery, the baby will be evaluated by a neurologist.
Following birth, these babies will have a complete clinical examination to look for other abnormalities that may point to a genetic disorder. Most babies will not have symptoms and will be able to stay with their mother. An MRI is usually obtained after birth to confirm the diagnosis and evaluate for other abnormalities that were not seen in the prenatal imaging.
Children with agenesis of the corpus callosum should be followed closely in their development by their pediatrician and referred to a neurologist. A complete neurologic examination will evaluate mental status, muscle tone, reflexes and development. Genetic testing may be considered after birth if it was not previously performed.
Consultations with other pediatric specialists like cardiology, ophthalmology or audiology may be indicated if there are other associated findings noted. If there is concern for seizures, an electroencephalogram (EEG) may be obtained. Medications may be required to control seizures.
Infants with agenesis of the corpus callosum should be referred to early intervention programs. At school age, children should be evaluated by the school district to determine whether an individualized educational plan (IEP) is needed to support educational needs.
What Are the Long-Term Effects of Agenesis of the Corpus Callosum?
The neurodevelopmental outcomes in children with corpus callosum abnormalities are variable. The presence of other findings on fetal ultrasounds, fetal MRI and newborn imaging, as well as the underlying cause of the condition, may impact these outcomes.
In cases of confirmed isolated partial or complete agenesis of the corpus callosum, nearly three-fourths of children can be expected to have a normal neurodevelopmental outcome. The remainder may have a combination of mild to moderate impairment in gross motor, fine motor and language skills.
The most commonly reported abnormalities of neurodevelopment in children with complete agenesis of the corpus callosum are related to difficulties in language skills, math, visual and special reasoning and attention skills. Deficits in problem solving and social skills are also common. Children with isolated agenesis of the corpus callosum also have a higher risk of epilepsy (predisposition to having seizures). Importantly, the outcomes are more likely to be abnormal in children who have additional abnormalities of the brain or other organs, or if a genetic disorder is identified.
Throughout childhood, the nerve fibers of the corpus callosum continue to grow and become more efficient, even through the teenage years. When they reach adolescence, children with a normally formed corpus callosum make progress in their abstract reasoning and problem solving, and their social skills mature. A child with agenesis of the corpus callosum may keep up with his or her peers until this phase of development, when they may begin to fall behind in schoolwork and social functioning. Thus, the symptoms of agenesis of the corpus callosum can become more evident as a child grows into adolescence and young adulthood.