Aplasia of the corpus callosum

A malformation in the form of a complete or almost complete absence of adhesion of nerve fibers connecting the hemispheres of the brain is defined as aplasia of the corpus callosum, which is synonymous with its agenesis, that is, its lack of development during development. [1]

Epidemiology

Congenital malformations of the brain account for at least 25% of all anomalies of the embryonic period of ontogenesis.

According to some reports, abnormalities of the corpus callosum, including its agenesis (aplasia), are detected in 0.3-0.7% of patients who, according to indications, undergo an MRI of the brain.

Isolated aplasia of the corpus callosum in children is a rare congenital defect, but it is considered a fairly frequent congenital anomaly as part of genetically determined syndromes, the prevalence of which is estimated at 230 cases per 10 thousand children with developmental problems.

In a third of cases of aplasia or partial agenesis of the corpus callosum, mental disorders are noted.

Causes of the aplasia of the corpus callosum

Aplasia of the corpus callosum (corpus callosum), which provides communication between the  cerebral hemispheres  and their coordinated functioning, is a congenital defect, and in most cases, doctors cannot determine its exact causes. But most often these are chromosomal abnormalities that affect the intrauterine formation of the cerebral structures of the fetus, or a hereditary anomaly, which is part of genetic syndromes with  malformations of the brain .[2]

So, the corpus callosum is not formed in the fetus with extra chromosome syndromes (trisomies), which include the Varkani, Patau, Edwards syndromes.

The absence of the corpus callosum was revealed in genetically determined Movat-Wilson syndrome, Aicardi syndrome, Marden-Walker syndrome; Donna-Barrow, Anderman, Proud, Apert syndromes, X-linked hydrocephalus syndrome. And partial aplasia of the corpus callosum is characteristic of Pitt-Hopkins, Dandy-Walker, Sensenbrenner syndromes.

The formation of the corpus callosum is impaired with abnormalities of the convolutions of the brain, for example, schizencephaly, or with congenital encephalocele and cysts of brain structures (as in the case of Chudley-McCullough syndrome), as well as malformation or  Arnold-Chiari syndrome .[3]

Risk factors

Among the probable risk factors for aplasia of the corpus callosum and other congenital cerebral defects, there are teratogenic effects on the embryo of increased radiation and various toxins; alcohol and drugs used during pregnancy; use of certain medications and viral infections of the mother.

There is also an increased risk of this defect in a child with a  family history of developmental disorders and  dysgenesis of the brain .

Pathogenesis

The corpus callosum begins to form in the sixth to eighth week of pregnancy, but disturbances in this process can occur between the third and fifteenth weeks of gestation. In embryology, the pathogenesis of the absence of the corpus callosum is associated with two biological mechanisms.

First, this can be explained by defects in genes that regulate and coordinate dorsolateral migration - the movement of embryonic neural crest cells (exodermal cell cord at the edges of the neural tube) or the mesendoderm of the head to the sites of formation of brain structures. Most embryonic defects and birth defects are the result of a violation of this process.

Another mechanism of agenesis of the corpus callosum may be that the axons of neurons in the neocortex do not cross the midline between the cerebral hemispheres of the embryo, and instead of the formation of a fibrous tract between the right and left hemispheres, abnormal bundles of nerve fibers are formed, which are located longitudinally - without connecting the cerebral hemispheres. [4]

Symptoms of the aplasia of the corpus callosum

What symptoms are caused by a violation of the interaction between the cerebral hemispheres in the absence of a connection between them, which should be provided by the corpus callosum?

In infants, the first signs may be feeding problems and frequent seizures. But in the presence of congenital syndromes, the clinic includes their symptoms, including abnormalities of the skull (microcephaly), facial skeleton (micrognathia) and facial features; oligodactyly or lack of fingers; spasticity and contractures of the joints, etc.[5]

With aplasia of the corpus callosum, a child may have visual and hearing impairments, decreased muscle tone and poor coordination of movements - with a significant delay in the onset of walking and the development of motor skills. There are also cognitive impairments (with inability to perceive information, attention deficit and speech problems), and behavioral abnormalities (often similar to autism).[6]

Complications and consequences

Aplasia of the corpus callosum has consequences and complications that vary depending on the associated brain abnormalities. Children with the most severe malformations of the brain may have seizures, spasticity,  hydrocephalus , and impaired physical and mental development.

Diagnostics of the aplasia of the corpus callosum

To establish a genetic diagnosis, molecular genetic studies, chromosomal and subtelomeric analyzes are carried out. In prenatal pediatrics, genetic testing is practiced during pregnancy - with the help of amniocentesis (analysis of amniotic fluid).[7]

Only instrumental diagnostics are capable of identifying pathology:

• computed tomography of the brain
• magnetic resonance imaging (MRI) of the brain

Visualization allows to establish the presence of such specific structural features of partial aplasia as a rudimentary rostrum (anterior corpus callosum) or aplasia of the posterior corpus callosum - radiatio corporis callosi and splenium. [8]

Differential diagnosis

To identify and distinguish other pathologies of the corpus callosum - dysgenesis (defective development), hypoplasia (partial underdevelopment), atrophy or hypoplasia of the corpus callosum, as well as to confirm the presence of a genetic syndrome - differential diagnosis is performed. [9]

Treatment of the aplasia of the corpus callosum

There are no methods to restore the corpus callosum to its normal state. Therefore, treatment may consist in reducing the severity of the symptoms of this defect:

• the use of anticonvulsants;
• physiotherapy, electroconvulsive therapy (to increase muscle strength and improve coordination of movements); [10]
• speech therapy;
• development of basic skills through occupational therapy.

Prevention

As a prophylaxis, only the prevention of teratogenic effects of various factors and prenatal diagnosis of congenital diseases can be considered  .

Forecast

In general, the prognosis depends on the degree and severity of the manifestations of aplasia of the corpus callosum and the presence / absence of concomitant malformations. [11]

In children with mild cases of this congenital anomaly, its negative neuropsychiatric consequences can be minimal with almost normal functioning. And as adults, some people without a corpus callosum have average intelligence and live normal lives.