Agenesis of the corpus callosum (ACC) is a rare congenital disorder, resulting from developmental defects during the embryonal formation of the corpus callosum. The corpus callosum is a band of tissue connecting the two cerebral hemispheres. Its development begins during the fifth week of embryonal life, and an interruption results in either total or partial dysgenesis. The symptoms of CCA vary greatly according to the extent of dysgenesis. Generally, patients present with hypotonia, vision impairment, seizures, spasticity, motor co-ordination problems, and, abnormal facial features. Mental retardation may also be seen in some patients. ACC is also seen associated with other neurological disorders, such as Aicardi Syndrome, Andermann Syndrome, Dandy Walker Syndrome, Arnold Chiari Malformation, and Acrocallosal Syndrome.
Brain scans (MRI or CT) are the only way to confirm ACC. In fact, prenatal scans are used to identify the anomaly within the growing fetus. Unfortunately, no treatment exists for the condition. Children who show clinical features of ACC may benefit form developmental and educational therapies.
There are various theories on the pathophysiology of ACC. Although many a times, ACC is believed to result from an infection or an injury during development, it has also been postulated to be a genetic defect transmitted in an autosomal recessive or an X-linked dominant fashion. This is supported by the fact that several genetic disorders have ACC as one of their presenting features. In addition, several chromosomal loci have been found to be consistently deleted in patients with ACC. Trisomy in chromosome 18, 13, and 8 have also been reported in the condition. However, the causative gene or the exact genetic loci responsible for the condition are yet unknown.
Chacko et al. (2001) reported the neurological and systemic abnormalities in 22 children with corpus callosum, seen in a hospital over a period of five years (1993-1997). All children with various neurological problems who were found to have corpus callosum agenesis on CT scan of the brain were included in the study. The patients were examined for syndromes association or metabolic defects, and were investigated with complete blood count, liver and renal function tests, karyotyping, electroencephalogram (EEG), electrocardiography, TORCH serology and thyroid function test. In some children, muscle biopsy, electromyography (EMG), and MRI of the brain were done. During the five year period, out of 2164 children who underwent CT scan of the brain for different reasons, 22 (1.02%) had corpus callosum agenesis. There were 14 males and eight females (mean age at presentation: 2-years and 8-months). The common presentations were seizures (36%) and developmental delay (23%). Cortical atrophy was the most common brain anomaly on CT scan. The chromosome analysis done in eight patients was normal. The selected group included two siblings with CCA; Chacko et al. (2001) were not able to screen their other family members and suggested autosomal recessive inheritance. Another patient with Aicardi Syndrome was found to have an X-linked recessive inheritance of ACC. Since the radiological diagnosis of corpus callosum agenesis was mostly coincidental, Chacko et al. (2001) emphasized on the importance of neuro-radiological imaging in the diagnosis of developmental delay.
Koul et al. (2006) analyzed data from the pediatric neurology department at Sultan Qaboos University Hospital for children undergoing evaluation for developmental delay and epilepsy. Corpus callosum agenesis was the most common neuronal migrational disorder, with 22 patients (55%). Corpus callosum agenesis data were from 1993 to 1997. The ages of affected children ranged from 2 days to 10 years, with a mean age of 2 years 8 months. There were 14 boys and 8 girls. The majority, 20 of 22 cases of corpus callosum agenesis, were nonsyndromic. Corpus callosum agenesis was detected in 1% of all computed tomographic (CT) scans of children less than 12 years age. Eight children (four boys and four girls) in this group had epilepsy. These were infantile spasms in four, generalized tonic-clonic seizures in two, and Lennox-Gastaut syndrome in two.
Alorainy (2006) reviewed and analyzed the MRI studies on 808 pediatric patients (aged 3 days to 15 years) over a 3-year period. A total of 114 congenital cerebral malformations were identified in 86 of these patients via MRI. Three patients were identified with Joubert Syndrome. Corpus callosum dysgenesis, diagnosed in 22 patients, was one of the most common malformations. Among patients with this condition, the entire corpus callousm was absent in 10 patients. In nine, corpus callousm was partially affected, in one patient there was global hypoplasia of corpus callosum with no signs of agenesis, while in two patients, part of the body of corpus callosum was not developed.