Agenesis of the corpus callosum: what is it, symptoms, treatment, prognosis

What is agenesis of the corpus callosum?

Agenesis of the corpus callosum (AMT) is one of several disorders of the corpus callosum, the structure that connects the two hemispheres (left and right) of the brain. With AMT, the corpus callosum is partially or completely absent.

The disorder is caused by an abnormal migration of brain cells during fetal development. AMT can occur as an isolated condition or in combination with other cerebral disorders, including Arnold-Chiari malformation, dandy-walker syndrome, schizencephaly (clefts or deep sections in the tissues of the brain) and holoprosencephaly (the inability of the forebrain to divide into lobes).

Girls may have a gender-specific condition called Aicardi syndromewhich causes severe cognitive impairment and developmental delays, epilepsy, abnormalities in the spine of the spine and retinal lesions.

AMT can also be associated with malformations in other parts of the body, such as midline facial defects. The consequences of the disorder range from subtle or mild to severe, depending on the associated abnormalities in the brain. Children with the most severe malformations of the brain may have intellectual disabilities, seizures, hydrocephalus and spasticity.

Other disorders of the corpus callosum include dysgenesisin which the corpus callosum develops incorrectly or defectively, and hypoplasiain which the corpus callosum is thinner than usual. People with these disorders have a higher risk of hearing and heart problems than people with normal structures. Disruptions in social interaction and communication in people with corpus callosum disorder may overlap with behavior autism spectrum disorders.

Causes of agenesis of the corpus callosum

In most cases, the cause of agenesis of the corpus callosum is unknown. However, agenesis of the corpus callosum can be inherited as an autosomal recessive trait or an X-linked dominant trait. This disorder may also be due in part to an infection during pregnancy (intrauterine), which leads to abnormal development of the fetal brain.

Genetic diseases are defined by a combination of genes for a specific trait, which are found on chromosomes received from the father and mother.

Recessive genetic disorders occur when a person inherits the same abnormal gene for one trait from each parent. If a person receives one normal gene and one gene for a disease, the person will carry the disease but usually not show symptoms. The risk of two carrier parents passing on both defective genes and therefore having a sick child is 25% with each pregnancy. The risk of having a child who will be a carrier, like the parents, is 50% with each pregnancy. The chance that a child will receive normal genes from both parents and be genetically normal for a given trait is 25%. The risk is the same for men and women.

In X-linked dominant disorders, the woman will develop disease with only one X chromosome with the abnormal gene. However, a sick man always has a more serious condition. Sometimes sick men die before birth, so only women survive. And then only with one of the forms of agenesis of the corpus callosum, known as Aicardi syndrome. Most of the patients diagnosed to date have been women. Aicardi syndrome is sometimes seen in men with an extra X chromosome.

Signs and symptoms

Agenesis of the corpus callosum (AMT) may initially become evident after the onset of seizures during the first weeks of life or within the first two years. However, not all people with AMT have seizures.

Other symptomsthat can begin at an early age are feeding problems and delays in keeping the head upright. There may also be delays in sitting, standing and walking. Impaired mental and physical development and / or accumulation of fluid in the skull (hydrocephalus) are also symptoms of this early type of disorder.

Neurological examination of AMT patients reveals:

• non-progressive mental retardation;
• impaired hand-eye coordination;
• deterioration of visual or auditory memory.

In some mild cases, symptoms may not appear for years. Elderly patients are usually diagnosed with tests for symptoms such as epilepsy, monotonous or repetitive speech, or headaches. In mild cases, the disorder may be overlooked due to the lack of overt symptoms in childhood.

Some patients may have deep-set eyes and a protruding forehead. An abnormally small head (microcephaly) or sometimes an unusually large head (macrocephaly) may be present.

In other cases, AMT is observed:

• wide-set eyes (teleanthus);
• small nose with inverted (anteverted) nostrils;
• abnormal ears;
• excessive skin on the neck;
• short arms;
• decreased muscle tone (hypotension);
• laryngeal anomalies;
• heart defects.

Aicardi syndrome, believed to be inherited as a dominant X-linked disorder, consists of agenesis of the corpus callosum, infantile spasms, and abnormal eye structure. This disorder is an extremely rare congenital disorder in which there are frequent attacks of epilepsy, anomalies of the middle layer of the eye (choroid) and retinal layers, lack of a structure connecting the two hemispheres of the brain (corpus callosum), accompanying severe mental backwardness. Aicardi syndrome is mainly observed in women.

Andermann's syndrome, identified in 1972, is a genetic disorder characterized by a combination of agenesis corpus callosum, mental retardation and progressive sensorimotor disorders of the nervous system (neuropathies). The gene responsible for this rare form of agenesis of the corpus callosum has recently been identified and genetic testing for this gene is now available (SLC12A6).

X-linked lissencephaly with ambiguous genitals Is a rare genetic disorder in which men have a small and smooth brain (lissencephaly), a small penis, severe mental retardation and intractable epilepsy. It is caused by mutations in the ARX gene. In women, the same mutations can only cause AMT, while less severe mutations in men can cause mental retardation. Genetic testing for this disorder is also available.

Diagnostics

Basically, ultrasound and magnetic resonance imaging (MRI) are imaging techniques that aid in the diagnosis of agenesis of the corpus callosum.

AMT is often diagnosed within the first two years of a child's life. An epileptic seizure may be the first symptom indicating that a child should be evaluated for brain dysfunction. The disorder can also be asymptomatic in the mildest cases for many years.

Treatment of agenesis of the corpus callosum

Treatment is symptomatic and supportive. Anticonvulsants, special education, physical therapy, and related procedures may be helpful depending on the range and severity of symptoms. If hydrocephalus is present, it can be treated with a surgical shunt to drain fluid from the brain cavity, thereby relieving the increased pressure on the brain. Genetic counseling can also be beneficial for families with this disorder.

Prognosis and complications of agenesis of the corpus callosum

The prognosis depends on the degree and severity of the malformation. Intellectual disabilities do not deteriorate. People with corpus callosum disorder tend to have delays in reaching milestones such as walking, talking, or reading; problems with social interaction; clumsiness and poor coordination of movements, especially with regard to skills that require coordination of the left and right hands and feet (such as swimming, cycling, and driving car), as well as problems of mental and social perception, which become more evident with age, with problems especially evident in the lower grades of school during adulthood.