The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers ... The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
The most frequent clinical findings in patients with ACC are mental retardation (60%), visual problems (33%), speech delay (29%), seizures (25%), and feeding problems (20%) (Schell-Apacik et al., 2008).
In 2 brothers and a sister, da-Silva ... The most frequent clinical findings in patients with ACC are mental retardation (60%), visual problems (33%), speech delay (29%), seizures (25%), and feeding problems (20%) (Schell-Apacik et al., 2008). In 2 brothers and a sister, da-Silva (1988) described a lethal and perhaps previously undescribed syndrome of hypoplastic corpus callosum, microcephaly, severe mental retardation, preauricular skin tag, camptodactyly, growth retardation, and recurrent bronchopneumonia. Death occurred at 32 months, 23 months, and 10 months. Naritomi et al. (1994) described what they called the da-Silva syndrome in a 6-month-old Japanese boy with agenesis of the corpus callosum, hypertonicity, severe growth and psychomotor retardation, microcephaly, large prominent ears, and delayed bone age. At age 7 years, his growth and mental development was severely retarded. Persistent hypertonia resulted in dislocation of the left hip joint and a bedridden state. Cardiac catheterization showed an atrial septal defect and partial anomalous pulmonary venous return. Schell-Apacik et al. (2008) performed a retrospective study of 172 patients with reported corpus callosum abnormalities and 23 patients with chromosomal rearrangements associated with corpus callosum abnormalities. A review of neuroimaging studies, when available, revised the findings in 43 cases and showed that 19 cases did not have corpus callosum abnormalities. Genetic or cytogenetic abnormalities were found in 13 (32%) of 41 cases studied in further detail.
Dobyns (1996) reviewed the genetics of agenesis of the corpus callosum and noted that ACC has been reported in more than 20 autosomal malformation syndromes. These include Miller-Dieker syndrome (MDLS; 247200), Rubinstein-Taybi syndrome (RSTS; 180849), acrocallosal syndrome (ACLD; ... Dobyns (1996) reviewed the genetics of agenesis of the corpus callosum and noted that ACC has been reported in more than 20 autosomal malformation syndromes. These include Miller-Dieker syndrome (MDLS; 247200), Rubinstein-Taybi syndrome (RSTS; 180849), acrocallosal syndrome (ACLD; 200990), and Joubert syndrome (JBTS; 213300). Dobyns (1996) also identified 17 X-linked malformation syndromes with ACC, including pyruvate dehydrogenase deficiency (312170). X-linked ACC is seen in patients with mutations in the L1CAM gene (308840), a cell surface glycoprotein implicated in migration of neurons and axonal growth: see X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (307000), the MASA syndrome (303350), and partial ACC (304100). Schell-Apacik et al. (2008) noted that ACC and dysgenesis of the corpus callosum has been associated with at least 7 autosomal dominant, 23 autosomal recessive, and 12 X-linked complex genetic syndromes. Schell-Apacik et al. (2008) were able to identify a genetic cause in 4 of 28 patients with complete ACC who had available neuroimaging results and underwent clinical evaluation. The cause remained unknown in the remaining patients.