AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Background

Agenesis of the corpus callosum (ACC) is an anomaly that may occur in isolation or in association with other CNS or systemic malformations. Because the corpus callosum may be partially or completely absent, the term dysgenesis has also been used to describe the spectrum of callosal anomalies.

Pathophysiology

Dysgenesis of corpus callosum is usually a sporadic occurrence, although the incidence is increased in patients with trisomy 18, trisomy 13, and trisomy 8. Several familial cases have been reported. Organ systems other than the CNS, particularly the musculoskeletal and genitourinary systems, may be affected as well.

Fibers of the corpus callosum arise from the superficial layers of the cerebral cortex and they project to the homotypic region of the contralateral cortex by passing through the corpus callosum while crossing the midline. Disturbance of embryogenesis in the first trimester of gestation by some unknown insult leads to failure of the callosal axons to pass across the midline. These arrested axons form the longitudinally oriented bundles of Probst that are located medial to the lateral ventricles in patients with agenesis.

Spectrum of abnormalities

ACC can be complete, partial, or atypical.

With complete agenesis, the corpus callosum is totally absent.

With partial agenesis (hypoplasia), the anterior portion (posterior genu and anterior body) is formed, but the posterior portion (posterior body and splenium) is not formed. The rostrum and the anterior/inferior genu are also not formed.

An atypical appearance occurs when the anterior to posterior formation is not respected.

In holoprosencephaly, callosal anomalies are atypical, eg, the splenium may be present without a genu or body. In middle interhemispheric fusion, a variety of holoprosencephaly, the genu and splenium may be present without the callosal body.

With pseudo corpus callosum, in conditions of complete or partial agenesis, the hippocampal commissure may become enlarged and appear like the posterior part of the corpus callosum.

Secondary destruction of corpus callosum occurs when the genu and anterior body are destroyed, leaving the posterior portion of the corpus callosum intact. This can occur secondary to porencephaly or schizencephaly, in transcallosal surgical approaches to the lateral and third ventricle, and with hemisection of the callosum for the treatment of seizures.

Other cerebral malformations may coexist with callosal dysgenesis. Examples of these include interhemispheric cysts; intracranial lipomas; and disorders of neuronal migration, such as schizencephaly, neuronal heterotopias, lissencephaly, and pachygyria.

Frequency of abnormalities

The frequencies of some of the more commonly associated anomalies are as follows:

• CNS anomalies (85%)
• Dandy Walker cyst (11%)
• Interhemispheric cysts
• Hydrocephalus (30%)
• Midline lipoma of corpus callosum (10%)
• Arnold-Chiari malformation (7%)
• Midline encephalocele
• Porencephaly
• Holoprosencephaly
• Hypertelorism median cleft syndrome
• Polymicrogyria
• Gray-matter heterotopia
• Cardiovascular, GI, and GU anomalies (62%)

Frequency

United States

The reported frequency is 0.7-5.3%.

International

The frequency is not known but could be similar to that in the US.

Mortality/Morbidity

• ACC may occur as an isolated defect, but it is frequently associated with other malformations, chromosomal abnormalities, and genetic syndromes.
• Although ACC has been found in asymptomatic individuals, it is generally considered a potential marker for neurologic impairment.
• In children, the prognosis is frequently related to other associated abnormalities.

Sex

ACC is reported to be more common in males than in females.

Age

ACC is a congenital or a developmental anomaly, and therefore, is present at the time of birth. In many cases, agenesis is diagnosed later in infancy or in childhood because of its associated congenital malformations.

Anatomy

Development and anatomy

The corpus callosum develops from the lamina reuniens in the telencephalon, and it begins to appear between the anterior and hippocampal commissures at about 10.5 weeks. The adult form of the corpus callosum is achieved by 17 weeks' gestational age. Initial formation of the corpus callosum occurs in the genu and the body, progressing posteriorly. The anterior genu and rostrum develops last, folding back under the genu. The callosum thickens with increasing myelination.

When the corpus callosum is absent, the third ventricle is often high riding, extending superiorly between the lateral ventricles. On coronal imaging, a candelabra appearance occurs, with the third ventricle forming the central vertical portion and the lateral ventricles the peripheral arms of the candelabra. On axial imaging, the lateral ventricles are parallel.

Medial to the lateral ventricles, longitudinal bundles of white matter are present. These are known as Probst bundles and presumably would have formed a normal corpus callosum. Probst bundles are seen best on coronal or axial T1-weighted MRIs. The occipital horns of the lateral ventricles are dilated in patients with ACC, probably because of a deficiency of peritrigonal white matter fibers. This anatomic finding is known as colpocephaly. When the corpus callosum is absent, the cingulate gyrus is inverted, the normal cingulate sulcus is absent, and the medial cerebral sulci radiate toward the midline in a radial configuration. This finding is especially helpful in evaluating newborns in whom the corpus callosum is normally thin.

The hippocampal formations are frequently hypoplastic in patients with ACC, with resulting mild dilatation of the temporal horns. In partial callosal agenesis, the posterior body, splenium and rostrum are usually absent. Absence of the posterior body and splenium is especially common in patients with a Chiari II malformation. Barkovich has described the unusual absence of the genu or the midbody of the corpus callosum in patients with atypical or mild forms of holoprosencephaly.

Associated midline cysts are noted in some cases. The exact origin and nature of these cysts is controversial. While some of these cysts represent a dilated superiorly migrated third ventricle, others represent true midline cysts that may be lined by ependymal cells or by arachnoid membranes.

Types of midline cyst formation

Raybaud and Girard suggest that there are 3 types of midline cyst formation in association with agenesis or hypogenesis of the corpus callosum.

Type 1 is a large midline cyst that communicates with third ventricle and the lateral ventricles.

Type 2 is similar to type 1, associated cortical anomalies (eg, polymicrogyria, gray matter heterotopia, schizencephaly) are present.

Type 3 involves complex, multilocular cysts that are asymmetric and independent of the ventricles. Cortical malformations are uncommon. With large cysts, the ipsilateral lateral ventricle may be compressed, and the contralateral ventricle may be obstructed and enlarged (hydrocephalus). A CT cystogram may be helpful in identifying the communications between the loculations of the cysts and with the ventricles and in guiding the placement of a ventriculostomy shunt.

Associated anatomic abnormalities

Other anatomic abnormalities in patients with ACC include hydrocephalus; cephaloceles; and neuronal migration disorders such as lissencephaly, schizencephaly, gray matter heterotopias, pachygria, and polymicrogyria.

Clinical Details

The white matter fibers forming the corpus callosum predominantly connect symmetrical regions in the frontal, parietal, temporal, and occipital lobes. Experimental observations indicate that the corpus callosum allows the sharing of learning and memory between the two cerebral hemispheres.

The clinical manifestations of callosal agenesis can be described under 2 headings: nonsyndromic and syndromic.

Nonsyndromic forms are the most common. An unknown, though probably small, proportion of patients are completely asymptomatic, or more commonly, their condition is incidentally discovered during neuroimaging. Patients may present with mental retardation or delayed development, seizures, and cerebral palsy. Macrocephaly may be seen due to hydrocephalus sometimes associated with interhemispheric cysts.

A number of syndromes may be associated with ACC. Some of the more common ones include Dandy-Walker syndrome, Aicardi syndrome, fetal alcohol syndrome, and several of the trisomies.

Preferred Examination

The diagnosis of callosal agenesis depends on neuroimaging. In the newborn prior to closure of the anterior fontanelle, screening ultrasonography (US) can clearly show the absence of the corpus callosum, parallel lateral ventricles, interhemispheric cysts, hydrocephalus, and other related anomalies. US was the first imaging modality to allow direct sagittal imaging of callosal dysgenesis.

Antenatal diagnosis of ACC is possible from about 20 weeks' gestation. Characteristic intrauterine US findings include colpocephaly and parallel ventricular walls. CT findings are also diagnostic of ACC. Parallel lateral ventricles, colpocephaly, and extension of the third ventricle into the interhemispheric fissure are particularly pertinent findings. In patients with ACC and an interhemispheric cyst, the preoperative injection of nonionic water-soluble contrast material into the cystic loculations for CT enables assessment of the ventricular system or of the communication of the cystic components with one another.

MRI is currently the imaging procedure of choice in infants and children with ACC, even in patients who have previously undergone CT and US examinations. The multiplanar capability and high soft-tissue contrast possible with MRI permits confident diagnosis of ACC and its associated anomalies, especially neuronal migration anomalies or atypical forms of holoprosencephaly. These entities may be extremely subtle or indiscernible on CT or US images.

Limitations of Techniques

Both CT and US can depict ACC, but MRI is the preferred imaging modality because of its greater sensitivity for depicting associated cerebral anomalies.

DIFFERENTIALS

Section 3 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Other Problems to be Considered

Holoprosencephaly
Acrocallosal syndrome
Aicardi syndrome
Apert syndrome
Chromosomal anomalies (13, 18, 11q-, etc)

RADIOGRAPH

Section 4 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

Radiography no longer has a contributory role in the evaluation or follow-up of this condition.

CT SCAN

Section 5 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

Axial CT shows parallel ventricles and continuation of the interhemispheric fissure with the third ventricle in patients with ACC. Colpocephaly can easily be visualized.

Nonenhanced axial CT can show an interhemispheric cyst. In complex types of multilocular interhemispheric cysts associated with callosal agenesis, a CT cystogram or ventriculogram can be obtained after iohexol is introduced into the cyst to establish which of the CSF collections communicate with each other or with the ventricular system.

Degree of Confidence

Although CT findings can suggest the diagnosis, MRI and US show the anatomic findings of ACC better than CT. MRI is the preferred imaging modality, especially for the diagnosis of partial agenesis and for the depiction of associated anomalies.

MRI

Section 6 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

The MRI findings in ACC are clearly demonstrated on the sagittal projection. Sagittal T1-weighted images clearly demonstrate the exact extent of callosal dysgenesis. In complete agenesis, the corpus callosum is not visualized, whereas in a hypogenetic corpus callosum, the later forming structures are usually absent. Therefore, the corpus callosum may show a posterior genu; a posterior genu and anterior body; a genu and an entire body; or an entire genu, body, and splenium with the exception of the rostrum. The third ventricle may be high riding and interposed between the bodies of the lateral ventricles.

Loss of the supporting function of the corpus callosum results in upward bulging of the roof of the third ventricle into the interhemispheric fissure. This upward herniation of the distended third ventricle is generally referred to as the interhemispheric cyst, but it should not be confused with a true dorsal or arachnoid cysts of the interhemispheric fissure found in some cases of callosal agenesis. The herniated third ventricle or true cyst may be located in the midline, separating the cerebral hemispheres, or it may be located predominantly to one side of the falx or the other. The herniated third ventricle is of variable size, sometimes extending superiorly all the way to the inner table of the calvaria.

An arachnoid or dorsal cyst generally does not communicate with the third or lateral ventricles, and it may be multiseptated. Hemorrhage may occur within the cysts, markedly changing their signal intensity on MRIs.

Coronal and axial MRI sections are best for demonstrating the longitudinal callosal bundles of Probst. They represent nondecussated callosal fibers. Instead of crossing in the midline, these fibers deviate at the interhemispheric fissure to run along the medial borders of the lateral ventricles from the frontal paraolfactory cortex to the occipital region. Their volume is less than that of the fibers in the normal corpus callosum, and their size varies.

The anterior commissure is usually present and occasionally larger or smaller than normal. It is best seen on sagittal or axial T1-weighted images. The hippocampal commissure is usually absent or hypoplastic but sometimes may be enlarged. The lateral ventricles may have a colpocephalic appearance with a localized dilatation of the atria and occipital horns. The lateral ventricles are impressed upon superomedially by the adjacent bundles, which are more marked in the frontal regions where the bundles are thickest. They also appear widely separated and medially concave, with the upper corners turned up and pointed. This finding is called bull's horns or the bat-wing conformation. The foramen of Monro may be enlarged. The cingulate gyri are not rotated and the cingulate sulcus is absent with the resultant radial pattern of sulci in the medial surface of the cerebral hemisphere. This finding is helpful in evaluating the newborns in whom the corpus callosum is normally thin.

Keyhole dilatation of the temporal horns, secondary to incomplete inversion of the hippocampal formation, is often present. This finding indicates the intimate relationship between the development of the corpus callosum and the limbic system. A large percentage of patients with dysgenesis of the corpus callosum have a large interhemispheric cyst, which may or may not communicate with the ventricular system.

The cyst is frequently associated with hydrocephalus. The exact origin of the cyst is not known. Some suggest that it is a dilated third ventricle or a true arachnoid cyst. At autopsy, the lining of the cyst may contain ependymal or arachnoid cells. On MRIs, the cyst may have a high protein content, in which case, the signal intensity on the T1-weighted image is greater than that of CSF.

A pericallosal lipoma of the corpus callosum is seen as a high-signal-intensity mass on T1 weighted images usually dorsal to the corpus callosum, which may be associated with callosal dysgenesis.

The differential diagnosis of this condition is very limited owing to the characteristic imaging appearance. For example, in certain cases of hydrocephalus in infants it may be difficult sometimes to visualize a corpus callosum that is very thin. But on careful observation of the sagittal images on MR, the radial convergence of sulci that is seen with ACC is not seen and a thin corpus can usually be identified. The midline interhemispheric cysts may be confused with midline arachnoid cyst (suprasellar, collicular) or with prominent cavum septum pellucidum and cavum vergae.

Degree of Confidence

With the exception of US in the sagittal projection, MRI is best for directly visualizing the anatomic appearance of the corpus callosum. The neuropathologic abnormalities intrinsic to callosal dysgenesis, as well as the associated brain anomalies, are portrayed in exquisite detail on sagittal, axial, and coronal MRIs. Only MRI can be used to reliably detect subtle partial callosal dysgenesis.

ULTRASOUND

Section 7 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Findings

Antenatal diagnosis of ACC is possible from about 20 weeks' gestation. Endovaginal US can contribute to the antenatal diagnosis of ACC. Findings suggesting ACC in utero are a disproportionate enlargement of the occipital horns and an abnormally parallel course of the ventricular walls. The abnormal radiating pattern may not be evident until late in the third trimester.

Findings in coronal sonograms include the following: (1) enlarged atria and occipital horns, (2) parallel and widely separated bodies of lateral ventricles, (3) an enlarged and upwardly displaced third ventricle, (4) absent corpus callosum and septum pellucidum, (5) frontal horns that are sharply angulated laterally and indented medially by the Probst bundles, (6) medial cerebral gyri and sulci with a radial pattern extending to the roof of the elevated third ventricle, and (7) elongation of the interventricular foramen of Monro.

An associated midline interhemispheric cystic lesion, a separate arachnoid cyst, or a communicating porencephalic cyst may be seen with US. Lipoma of the corpus callosum is demonstrated as a highly echogenic mass in the region of the corpus callosum.

Degree of Confidence

US, especially transvaginal US, helps in the prenatal diagnosis of nonchromosomal syndromes by enabling the detection of specific morphologic findings. In rare syndromes, the index case may not be prenatally diagnosed, but subsequent pregnancies may benefit from early diagnosis. However, MRI has been seen to be more helpful in the prenatal diagnosis of corpus callosal dysgenesis.

MULTIMEDIA

Section 8 of 9  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

Media file 1:  Corpus callosum, agenesis. Sagittal T1-weighted MRI of the brain shows the normal appearance of the corpus callosum.
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Media type:  MRI

Media file 2:  Corpus callosum, agenesis. Sagittal T1-weighted MRI of the brain shows complete absence of the corpus callosum. The cingulate sulcus is absent and the medial hemispheric sulci reach the third ventricle in a radial fashion.
	View Full Size Image
Media type:  MRI

Media file 3:  Corpus callosum, agenesis. Sagittal T1-weighted MRI of the brain shows partial agenesis of the corpus callosum. The genu and anterior body of the corpus callosum are visualized, while the posterior body, splenium, and the rostrum are absent.
	View Full Size Image
Media type:  MRI

Media file 4:  Corpus callosum, agenesis. Axial nonenhanced CT of the brain shows colpocephaly due to dilated atria and occipital horns of the lateral ventricle. Note the parallel configuration of the lateral ventricles. Also, noted incidentally is interdigitation of gyri from fenestration of the falx.
	View Full Size Image
Media type:  CT

Media file 5:  Corpus callosum, agenesis. Axial T1-weighted MRI shows that the lateral ventricles are parallel to each other and do not come into contact with each other as they normally should.
	View Full Size Image
Media type:  MRI

Media file 6:  Corpus callosum, agenesis. Coronal T1-weighted MRI of the brain shows absence of the normal corpus callosum. The lateral ventricles form a bull's-horn appearance and are indented medially by the Probst bundle (arrows).
	View Full Size Image
Media type:  MRI

Media file 7:  Corpus callosum, agenesis. Sagittal T1-weighted MRI of the brain. Parasagittal section through the lateral ventricle shows dilatation of the atrium and occipital horn (colpocephaly).
	View Full Size Image
Media type:  MRI

Media file 8:  Corpus callosum, agenesis. Sagittal T1-weighted MRI of the brain shows apparent atypical callosal dysgenesis in lobar holoprosencephaly. The body and splenium of the corpus callosum are well formed while the genu and rostrum are hypoplastic.
	View Full Size Image
Media type:  MRI

Media file 9:  Corpus callosum, agenesis. Axial T2-weighted MRI of the brain shows apparent atypical callosal dysgenesis in lobar holoprosencephaly (same patient as in Image 8). There is fusion across the midline of the inferior basal ganglia (arrow) and the medial cortex of the frontal lobes across the interhemispheric fissure (arrowhead).
	View Full Size Image
Media type:  MRI

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Multimedia
• References

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• Vergani P, Ghidini A, Strobelt N, et al. Prognostic indicators in the prenatal diagnosis of agenesis of corpus callosum. Am J Obstet Gynecol. Mar 1994;170(3):753-8. [Medline].

Article Last Updated: Mar 11, 2004