The corpus callosum is a major pathway connecting the two hemispheres of the brain. The development of the corpus callosum begins during the 5th week of fetal life with the formation of the primitive lamina terminalis, which thickens to form the commissural plate. Glial cells coalesce to form a bridge-like structure that serves as a guide for the callosal fibers crossing the longitudinal cerebral fissure to their targets on the contralateral side of the brain (Rakic and Yakovlev, 1968). The mature corpus callosum is formed by the 17th week of gestation. In agenesis of the corpus callosum (ACC), the commissural fibers do not cross the midline; instead they form thick bundles of fibers, called “Probst bundles,” which course in a posterior direction along the medial walls of the lateral ventricles. These bundles indent and separate the anterior horns of the lateral ventricles.

ACC may be an isolated finding; however, it is frequently associated with other malformations and genetic syndromes including chromosomal aberrations and inborn errors of metabolism (Parrish et al., 1979; Jeret et al., 1987; Dobyns, 1989). Associated central nervous system (CNS) abnormalities include Chiari malformations, anomalies of neuronal migration including lissencephaly, schizencephaly, pachygyria and polymicrogyria, encephaloceles, Dandy–Walker malformations, holoprosencephaly, and olivopontocerebellar degeneration (Barkovich and Norman, 1988). Extracranial malformations include abnormalities of the face and of the cardiovascular, genitourinary, gastrointestinal, respiratory, and musculoskeletal systems (Parrish et al., 1979; Franco et al., 1993; Kozlowski and Ouvrier, 1993).

ACC has been estimated to occur in 0.3% to 0.7% of the general population and in 2% to 3% of the developmentally disabled population (Freytag and Lindenberg, 1967; Grogono, 1968; Jeret et al., 1986). In a large series of patients diagnosed with a metabolic disease, 17% were shown to have an abnormality of the corpus callosum by computed tomography (CT), ultrasound, or autopsy examination (Bamforth et al., 1988).

In a series of 4122 perinatal or neonatal autopsy specimens, the incidence of CNS malformations was 8.8%, and of the 363 CNS malformations diagnosed, ACC accounted for 4.1% (Pinar et al., 1998).

Usually only midsagittal and midcoronal scans of the fetal brain allow clear visualization of the corpus callosum. Such views can be obtained with standard transabdominal ultrasound examination of most fetuses in breech position or transverse lie. For fetuses in the vertex position, transvaginal sonography is the preferred technique.

On sagittal scan, the corpus callosum appears as a sonolucent band, demarcated superiorly and inferiorly by two echogenic lines. The superior line arises from the pericallosal cistern; the inferior line derives from the fornix and roof of the cavum septum pellucidum. Color Doppler sonography can demonstrate the pericallosal artery, a branch of the anterior cerebral artery that sweeps in a circular pattern over the corpus callosum. In a coronal scan, the corpus callosum appears to form the roof of the cavum septum pellucidum and frontal horns.

Classic neuroradiologic signs for the diagnosis of ACC on pneumoencephalography were described by Davidoff and Dyke (1934). Their criteria have been applied to the CT diagnosis and also can be applied to sonography (Skidmore et al., 1983). The findings include the absence of the corpus callosum and cavum septum pellucidum and a variety of indirect findings, including

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   increased separation of the frontal horns and bodies of the lateral ventricles;

   
   
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   relative dilatation of the occipital horns of the lateral ventricles;

   
   
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   concave medial border of the lateral ventricles due to protrusion of the Probst bundles;

   
   
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   general dilatation and upward displacement of the third ventricle;

   
   
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   abnormal radial orientation of the medial cerebral gyri (Comstock et al., 1985; Bertino et al., 1988; Sandri et al., 1988; Pilu et al., 1993; Maheut-Lourmiere and Paillet, 1998).

In a series of 141 cases of fetal cerebral ventriculomegaly, ACC was noted in 16 cases (11%) (Valat et al., 1998). In another series of 82 cases of mild ventriculomegaly, there were 7 cases (9%) of ACC (Vergani et al., 1998). The finding of mild ventriculomegaly during routine prenatal sonography should, therefore, prompt a targeted search to confirm the presence of the corpus callosum.

Ultrasound diagnosis of ACC is more difficult prenatally than postnatally. The earliest prenatal diagnosis has been made at 19 weeks of gestation (Pilu et al., 1993). Because the corpus callosum is not normally formed until 18 weeks, most reported cases have been diagnosed in the third trimester (Bertino et al., 1988; Bennett et al., 1996). This difficulty in prenatal diagnosis is usually due to the fact that the characteristic ventricular abnormalities can be quite subtle on the axial views of the fetal cranium that are most commonly obtained. It is preferable to use coronal and sagittal views to diagnose the characteristic ventricular abnormalities; however, these views are not as commonly used prenatally.

Routine sonography of the fetal brain is usually performed with axial scans that do not allow visualization of the corpus callosum. However, enlargement of the atria of the lateral ventricles is readily appreciated with these views. In the largest series of prenatally diagnosed ACC, 34 of 35 fetuses had atrial measurements 10 mm (Pilu et al., 1993). Once atrial enlargement has been observed, other sonographic findings may identify possible ACC. The most consistent and easy-to-identify finding is the teardrop configuration of the lateral ventricles (Figure 6-1). In the axial plane, enlargement of the atria and occipital horns and separation of the bodies combine to generate a pattern that is readily recognizable. The teardrop configuration of the ventricles has not been documented in conditions other than ACC, and it is believed to be a specific sign for the diagnosis of callosal agenesis (Pilu et al., 1993). In order to document the callosal lesion directly, it is important to obtain midcoronal and midsagittal scans when a dilated atrium or teardrop ventricle is identified.

Prenatal diagnosis of partial ACC has been reported (Figure 6-2) (Lockwood et al., 1988; Pilu et al., 1993). The natural history of partial ACC is uncertain, and cerebral findings associated with it are probably more subtle than with the complete form. It is expected that antenatal diagnosis will not be possible in many cases. The cavum septum pellucidum is not identified in cases of complete ACC but may be visualized in cases of partial agenesis. Sonographic evaluation of the structure is potentially helpful in routine screening, alerting the sonologist to perform more coronal and sagittal scans for direct visualization of the corpus callosum. Widening of the interhemispheric fissure and upward displacement of the third ventricle can be documented in approximately half of the prenatal cases. Radial arrangement of the medial cerebral sulci has been seen only in third trimester studies. This is presumably because the surface of the hemispheres is smooth in the second trimester, with secondary sulci appearing only at the onset of the third trimester. In many cases of ACC, prenatal ultrasound examination may only cause one to suspect the diagnosis, while prenatal magnetic resonance imaging (MRI) may be needed to accurately confirm the diagnosis (Glenn et al., 2005). In one series of 14 cases of ACC, ultrasonography confirmed the diagnosis in only 4 cases, while MRI confirmed the diagnosis in 13 cases (d’Ercole et al., 1998). In another series of 20 cases of ACC, prenatal MRI made a positive diagnosis in 19 cases (Brisse et al., 1998). In a recent series of 10 cases of callosal abnormalities suspected by ultrasound examination, 8 cases were confirmed by MRI and 2 cases were found to have a normal corpus callosum (Glenn et al., 2005). MRI was also useful in identifying additional brain abnormalities that were not apparent by sonography such as abnormal sulcation. Sixty-three percent of cases (5/8) with confirmed callosal abnormalities on both ultrasound examination and MRI were found to have additional abnormalities on MRI. These occult findings were confirmed on postnatal MRI or autopsy in three of five patients. The information obtained by MRI is invaluable for patient counseling since additional brain abnormalities have been associated with worse long-term outcomes. In addition, three-dimensional ultrasound examination may also be useful to confirm the diagnosis (Kalache et al., 2006; Pilu et al., 2006).