Introduction
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.1,2,3,4,5,6
Corpus callosum, agenesis. Sagittal T1-weighted MRI of the brain shows the normal appearance of the corpus callosum.
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.
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, whereas the posterior body, splenium, and the rostrum are absent.
Recent studies
Moes et al studied 720 individuals with agenesis of the corpus callosum to develop a profile of characteristics and diagnostic indications and identified the following: delayed motor development, difficulty with balance and bimanual movements, large head size, poor muscle tone, poor depth perception, reduced pain perception, sleeping difficulties, and an increased proportion of left- and mixed-handedness.7
Tang et al did a retrospective study of 29 fetuses with agenesis of the corpus callosum, including fetal MR imaging, postnatal MR imaging, and autopsy findings. A total of 23 fetuses had delayed sulcation and/or too-numerous cortical infoldings; 15 fetuses had cerebellar and/or brainstem abnormalities. Fetal MR imaging findings suggested a genetic syndrome in 5 fetuses and an acquired etiology or genetic/metabolic disorder in 2 fetuses. Findings were confirmed in 8 cases with postnatal MR imaging, except for delayed sulcation and small vermis, and in 4 cases with autopsy, except for periventricular nodular heterotopia and abnormalities in areas not examined by autopsy. Neurodevelopmental outcome was good in 7 and poor in 9 children. Abnormal sulcal morphology and/or infratentorial abnormalities were present in those with poor outcome and absent in those with good outcome.8
Pathophysiology
Agenesis of the corpus callosum (ACC) 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.5,9,10
Fibers of the corpus callosum arise from the superficial layers of the cerebral cortex; they project to the homotypic region of the contralateral cortex by passing through the corpus callosum in 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 may 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; for example, the splenium may be present without a genu or body. In middle interhemispheric fusion, which is a variety of holoprosencephaly, the genu and splenium may be present without the callosal body.11
With pseudo–corpus callosum, which involves 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 may occur secondary to porencephaly or schizencephaly; as a surgical complication in cases involving the transcallosal approach 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 frequency of occurrence 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 of agenesis of the corpus callosum in the US is 0.7-5.3%.
International
Internationally, the frequency of agenesis of the corpus callosum is not known but could be similar to that in the US.
Mortality/Morbidity
- Agenesis of the corpus callosum 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
Agenesis of the corpus callosum is reported to be more common in males than in females.
Age
Agenesis of the corpus callosum is a congenital or a developmental anomaly and so 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; 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 develop 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 in patients with agenesis of the corpus callosum (ACC). These are known as Probst bundles and presumably would have formed a normal corpus callosum. Probst bundles are best seen 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.12
Associated midline cysts are noted in some cases. The exact origin and nature of these cysts are controversial. Whereas 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.13
Type 1 is a large midline cyst that communicates with the 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 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.
Presentation
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 2 cerebral hemispheres.
The clinical manifestations of callosal agenesis may be described under 2 headings: nonsyndromic and syndromic.14
Nonsyndromic forms are the most common. An unknown, though probably small, proportion of patients are completely asymptomatic; commonly, their condition is incidentally discovered during neuroimaging. Patients may present with mental retardation or delayed development; seizures; and cerebral palsy.7 Macrocephaly may occur as a result of hydrocephalus; it is 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, before closure of the anterior fontanelle occurs, screening ultrasonography (US) may clearly show the absence of the corpus callosum; it may also show parallel lateral ventricles, interhemispheric cysts, hydrocephalus, and other related anomalies. US was the first imaging modality to allow direct sagittal imaging of callosal dysgenesis.10,15,16,17,18
Antenatal diagnosis of agenesis of the corpus callosum (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 who have an interhemispheric cyst, the preoperative injection of nonionic water-soluble contrast material into the cystic loculations for CT evaluation 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 that are possible with MRI permit 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
Agenesis of the corpus callosum may be depicted on both CT and US, but MRI is the preferred imaging modality because of its greater sensitivity for depicting associated cerebral anomalies.
Differential Diagnoses
Other Problems to Be Considered
Holoprosencephaly
Acrocallosal syndrome
Aicardi syndrome
Apert syndrome
Chromosomal anomalies (13, 18, 11q-, etc)
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References
Barkovich AJ. Pediatric Neuroimaging. 3rd ed. Philadelphia: Lippincott Williams & Wilkins;2000: 254-66.
Taylor M, David AS. Agenesis of the corpus callosum: a United Kingdom series of 56 cases. J Neurol Neurosurg Psychiatry. Jan 1998;64(1):131-4. [Medline].
Schell-Apacik CC, Wagner K, Bihler M, Ertl-Wagner B, Heinrich U, Klopocki E, et al. Agenesis and dysgenesis of the corpus callosum: clinical, genetic and neuroimaging findings in a series of 41 patients. Am J Med Genet A. Oct 1 2008;146A(19):2501-11. [Medline].
Glass HC, Shaw GM, Ma C, Sherr EH. Agenesis of the corpus callosum in California 1983-2003: a population-based study. Am J Med Genet A. Oct 1 2008;146A(19):2495-500. [Medline].
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Dávila-Gutiérrez G. Agenesis and dysgenesis of the corpus callosum. Semin Pediatr Neurol. Dec 2002;9(4):292-301. [Medline].
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Pirola B, Bortotto L, Giglio S, et al. Agenesis of the corpus callosum with Probst bundles owing to haploinsufficiency for a gene in an 8 cM region of 6q25. J Med Genet. Dec 1998;35(12):1031-3. [Medline].
van Bon BW, Koolen DA, Borgatti R, Magee A, Garcia-Minaur S, Rooms L, et al. Clinical and molecular characteristics of 1qter microdeletion syndrome: delineating a critical region for corpus callosum agenesis/hypogenesis. J Med Genet. Jun 2008;45(6):346-54. [Medline].
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Barkovich AJ. Apparent atypical callosal dysgenesis: analysis of MR findings and their relationship to holoprocencephaly. AJNR. 1990;11:333-339. [Medline].
Utsunomiya H, Ogasawara T, Hayashi T, et al. Dysgenesis of the corpus callosum and associated telencephalic anomalies: MRI. Neuroradiology. Apr 1997;39(4):302-10. [Medline].
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d''Ercole C, Girard N, Cravello L, et al. Prenatal diagnosis of fetal corpus callosum agenesis by ultrasonography and magnetic resonance imaging. Prenat Diagn. Mar 1998;18(3):247-53. [Medline].
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Further Reading
Related eMedicine topic
Brain, Venous Vascular Malformations
Clinical guidelines
NINDS Agenesis of the Corpus Callosum Information Page. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. Accessed October 14, 2008.
ACC (Agenesis of the Corpus Callosum) Network. ACC Network. 5749 Merrill Hall Room 118.
University of Maine, Orono, ME 04469-5749 (207) 581-3119. um-acc@maine.edu. Accessed October 14, 2008.
The National Organization for Disorders of the Corpus Callosum. NODCC. PMB 363. 18032-C Lemon Drive. Yorba Linda, CA. Accessed October 14, 2008.
Keywords
agenesis of the corpus callosum, partial agenesis of the corpus callosum, hypoplasia of the corpus callosum, callosal agenesis, corpus callosum dysgenesis, callosal dysgenesis, dysgenesis of the corpus callosum, ACC, CCA
