Agenesis of the corpus callosum

Agenesis of the corpus callosum (ACC) is a birth defect in which the structure that connects the two hemispheres of the brain (the corpus callosum) is partially or completely absent due to an abnormality of development during the fetal period. The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. Intelligence may be normal with mild compromise of skills requiring matching of visual patterns. But children with the most severe brain malformations may have mental retardation, seizures, hydrocephalus, and spasticity.

Types
The types of agenesis of the corpus callosum are: complete agenesis of the corpus callosum (ACC), partial ACC, hypoplasia of the corpus callosum, and dysgenesis of the corpus callosum. [1]

Complete Agenesis
This condition occurs when the callosal fibers may have started to grow, but are unable to cross between the hemispheres. The fibers grow toward the back of the same hemisphere where they began. These fibers form what are called Bundles of Probst. Some smaller connections between the hemispheres develop in most individuals with ACC. These are the anterior commissure, posterior commissure, and hippocampal commissure. However, each of these is at least 40,000 times smaller than the corpus callosum. Thus, they cannot compensate completely for the absence of the corpus callosum.

Partial Agenesis
In partial ACC, the corpus callosum began to develop, but does not complete development. Since the corpus callosum develops from front to back, the part of the corpus callosum that is present in partial ACC usually will be toward the front of the brain, with the back portion missing. Partial ACC includes the entire range of partial absence, from absence of only a small portion of callosal fibers to absence of most of the corpus callosum. In partial ACC, the other smaller connections are usually present.

Hypoplasia
Hypoplasia means underdevelopment or incomplete development. In this type, the corpus callosum may extend through the entire area front-to-back as would a typical corpus callosum, but it looks notably thinner. It is unclear in this case if the callosal nerve fibers are fully functional and just limited in number, or if they are both less plentiful and more dysfunctional.

Dysgenesis
Dysgenesis means that the corpus callosum developed, but developed in some incomplete or malformed way. Thus, partial ACC and hypoplasia of the corpus callosum would be forms of dysgenesis, as would any other form of inadequate callosal development. Dysgenesis is a broad term for any malformation of the corpus callosum that is not a complete agenesis.

Signs and Symptoms
The common signs and symptoms of ACC include:


 * Problems with motor control and poor muscle tone


 * Visual problems


 * Mental retardation


 * Developmental delays


 * Speech and language delays


 * Feeding difficulties


 * Hearing impairment


 * Deformities of the face and head

ACC can occur as an isolated condition or in combination with other cerebral abnormalities, including Arnold-Chiari malformation, Dandy-Walker syndrome, Andermann syndrome, schizencephaly (clefts or deep divisions in brain tissue), and holoprosencephaly (failure of the forebrain to divide into lobes.)

Girls may have a gender-specific condition called Aicardi syndrome, which causes severe mental retardation, seizures, abnormalities in the vertebra of the spine, and lesions on the retina of the eye.

ACC can also be associated with malformations in other parts of the body, such as midline facial defects.

Causes
The exact cause of agenesis of the corpus callosum is not known. Possible causes include: [2]


 * Chromosomal (genetic) abnormalities (such as trisomy 8 or trisomy 18)


 * Prenatal infections, such as rubella (German measles)


 * Toxic exposures (like fetal alcohol syndrome)


 * Structural abnormalities (cysts) that interfere with normal development of the corpus callosum.

When one of these factors interfere with development of the fetal brain (between the fifth and sixteenth week of pregnancy), agenesis of the corpus callosum may result.

Diagnosis
Agenesis of the corpus callosum can be diagnosed in the fetus by ultrasound or Magnetic resonance imaging (MRI) of the head. After birth, the diagnosis can be made by ultrasound, MRI orComputed tomography (CT) scan.

Treatment
There is no standard course of treatment for ACC. Treatment usually involves management of symptoms and seizures if they occur.

Living with Agenesis of the Corpus Callosum
Agenesis of the corpus callosum may involve a number of different health care professionals. Ongoing care may require the assistance of a(n): neurologist, endocrinologist, geneticist, ophthalmologist, speech-language Therapist, occupational therapist, physical therapists, early intervention specialists, and social worker.

Patients may qualify for early intervention services (physical therapy, occupational therapy and speech therapy) and possibly for special education as they approach school age.

Chances of Developing Agenesis of the Corpus Callosum
According to the University of Maine ACC (Agenesis of the Corpus Callosum) Network [2], most sources estimate callosal disorders can occur in up to 4 individuals per 1,000 in the general population and occurs more frequently among persons with developmental disabilities (22-24 per 1,000). Recently, a group of researchers in the U.S. reported an incidence rate of 1 in 4,000 live births, based on a review of prenatal and neonatal imaging studies, but these researchers suggested this may be an underestimate of the true occurrence rate.

Clinical Trials
A list of ongoing clinical trials is available here: Agenesis of the Corpus Callosum trials

Research

 * A relationship between the corpus callosum and bipolar disorder is studied. Structural changes in the corpus callosum may cause problems integrating information across the cerebral hemispheres. This may play a role in the development of bipolar disorder. [3]


 * The incidence of ACC and hypoplasia of the corpus callosum in infants born in California between 1983 and 2003 was evaluated and found to be 1.8 per 10,000 live births. Infants with ACC were almost four times more likely to be born prematurely than those without ACC. In addition, an increase in the rate of abnormalities of the corpus callosum was associated with maternal age over 40 and other birth defects. [4]


 * Patients diagnosed prenatally with ACC and without other abnormalities had normal outcome or moderate disability on follow-up at three to sixteen years of age. [5]


 * The corpus callosum was found to be thinner in the temporal and parietal areas of the brain in a population of women with co-existing Borderline Personality Disorder (BPD) and Attention Deficit-Hyperactivity Disorder (ADHD).[6]

Expected Outcome
Prognosis depends on the extent and severity of malformations. ACC does not cause death in the majority of children. Mental retardation does not worsen. Although many children with the disorder have average intelligence and lead normal lives, neuropsychological testing reveals subtle differences in higher cortical function compared to individuals of the same age and education without ACC.