Agenesis of corpus callosum (ACC) [OMIM 217990] is one of the most common congenital cerebral malformations which is morphologically the complete or partial absence of corpus callosum, and not defined by functional or behavioral abnormalities (as in autism).
Corpus callosum is the largest white matter structure containing 200 million axons, connecting the two hemispheres of the brain. Its formation starts by 74 days of gestation, with the first fibers crossing the midline at 11 to 12 weeks of gestation, development getting completed by 115 days and the basic shape assumed by 18 to 20 weeks of gestational age. The formation is primarily from anterior to posterior, starting with the genu and finishing with the rostrum.
Agenesis of the corpus callosum can present as an isolated condition or associated with other cerebral abnormalities. Several factors have correlations with the etiology of agenesis of the corpus callosum:
Agenesis of the corpus callosum is one of the most common human brain malformations. It has an incidence of 0.5 to 70 in 10000, and its prevalence in children with developmental disabilities is about 230 in 10000 (2.3%). It presents in 1 in 19000 autopsies. Agenesis of the corpus callosum is more prevalent among males than females.
Research has not yet determined the precise mechanism underlying the isolated occurrence of agenesis of the corpus callosum. It is an abnormality of prosencephalic midline development, and there are more than 200 congenital syndromes which associated with ACC.
Depending on the part of corpus callosum affected, agenesis of the corpus callosum may classify into one of two varieties:
As a rule of thumb, primary agenesis of corpus callosum (total agenesis) can be excluded by the presence of the rostrum. One exception is holoprosencephaly. In this condition, there may be atypical callosal dysgenesis, in which anterior parts of the corpus callosum are absent.
Morphologically, agenesis of the corpus callosum classifies into two types:
Probst fiber bundles run parallel to the medial walls of the lateral ventricles and enlarge and deform their medial borders, especially at the level of the frontal horns. Recently a reduction in the number of von Economo neurons, which are large spindle-shaped neurons localized to the anterior cingulate cortex and frontoinsular cortex, has been described in agenesis of corpus callosum. Partial agenesis of corpus callosum has correlations with 'sigmoid bundles,’ which asymmetrically connect the frontal lobe with the contralateral occipitoparietal cortex.
The affected patients are mostly asymptomatic. Most of the patients present within the first two years of life.
Patients with agenesis of corpus callosum usually present with:
Isolated agenesis of corpus callosum patients may have normal intelligence quotient, but may have some cognitive deficits which group under the "core syndrome" which includes:
An antenatal ultrasound scan may show some findings suggestive of agenesis of the corpus callosum:
Magnetic resonance imaging of the brain is the investigation of choice for agenesis of the corpus callosum.
Neuropsychological evaluation of all patients with agenesis of the corpus callosum is mandatory.
Treatment is mainly symptomatic and supportive.
The main line of treatment includes:
The primary imaging differential diagnoses are holoprosencephaly and septo-optic dysplasia.
The main feature which helps to differentiate between the absence of septum pellucidum and agenesis of the corpus callosum is the presence of fused or communicating frontal horns and of the corpus callosum(which may sometimes appear thinned).
The presence of fused frontal horns, an abnormal anterior cerebral artery (azygos anterior cerebral artery), and absence of a normally developed interhemispheric fissure anteriorly in holoprosencephaly assist in differentiating it from isolated and complete agenesis of the corpus callosum.
Midline interhemispheric cysts may also be associated with agenesis of the corpus callosum. The differential diagnosis of such cysts are:
Sometimes these conditions can cause difficulty in diagnosis as a dilated third ventricle with a dorsal cyst can also appear the same. But the presence of choroid plexus in the roof of the third ventricle helps in differentiating the latter.
The prognosis is determined primarily by the associated malformations.
Agenesis of the corpus callosum is associated with the following intracranial anomalies (in decreasing order of frequency)
The children with isolated agenesis of the corpus callosum without any significant neurologic sequelae have the best prognosis.
The children with agenesis of corpus callosum associated with the neuronal migration disorder with or without Dandy-Walker malformation have the worst prognosis.
Complications are more likely to occur due to the associated disorders. Some of these include:
Patients with developmental delay and intellectual disabilities may benefit from early intervention services, special education, and other supportive therapies.
A multi-disciplinary approach involving the obstetrician for the antenatal care of the mother, neonatologist, pediatric neurologist, pediatric neurosurgeon, geneticist, maxillofacial surgeon, ophthalmologist, otorhinolaryngologist, plastic surgeon, pediatric psychiatrist and psychologist, dietician, and pediatric neuro nurse, working collaboratively in an interprofessional team approach can help to provide a good outcome for the patient with agenesis of corpus callosum.
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