Agenesis of the corpus callosum

 Luis F. Gonçalves, MD - Maria Verônica Munoz Rojas, MD

Florianopolis, Brazil

Updated 08.22.2007 by F.G.

Definition
Partial or complete absence of the corpus callosum, generally affecting the posterior aspect of the structure1

Incidence
30-70:10,000 for the general population and 2 to 3 % of those with mental disabilities.2-4

Etiology
The corpus callosum is a white matter structure located in the midline and composed of fibers that connect both cerebral hemispheres. Complete agenesis of the corpus callosum may occur after inflammatory or vascular lesions occurring after 12 weeks. Later insults result in partial agenesis of a previously normal corpus callosum; therefore, generally only the posterior portion is affected.1

Embryology
The development of the corpus callosum begins during the fifth 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. The mature corpus callosum is formed by the seventeenth week of gestation.5

Pathogenesis
Different mechanisms may result in agenesis of the corpus callosum (ACC). Among those, there are two forms of true ACC. In the first one, axons are formed but are incapable of crossing the middle because of the absence of "massa comissuralis"; instead, nerve fibers follow a caudal course, grouped in a thick longitudinal bundle (Probst bundle), below the cingulus and above the phornix; this bundle separates the anterior horns of the lateral ventricles and the third ventricle may be, at times, dislocated superiorly. In the second middle, ACC is caused by defects in the formation of commissural axons in the cerebral cortex.1

Diagnosis
Diagnosis is suspected when the posterior horn of the lateral ventricle is dilated, giving the ventricle a “tear drop” aspect. The third ventricle is usually dilated and dislocated towards the interhemispheric fissure. In coronal sections, it is not possible to visualize the corpus callosum. ACC is better documented in coronal and sagittal sections of the fetal brain; therefore, it may be necessary to perform a transvaginal examination.

Figure 1. Transverse section through the cerebral cortex demonstrating a "tear drop" shaped ventricle. Observe the relative dilation of the posterior horn of the lateral ventricle and separation of the anterior horns. Figure 2. Transverse section through the superior portion of the cortex of a fetus with ACC. Figure 3. A transverse section slightly below the one in Figure 2. The cavum septum pellucidum is not visualized.

 

Figure 4. Diagram representing the sagittal section of a normal brain. The corpus callosum is represented in gray.  Figure 5. Diagram representing the coronal section of a normal brain. The corpus callosum is observed as a bundle of fibers crossing the midline (represented in gray). Figure 6. Diagram representing a transverse section of a normal brain. The corpus callosum is observed as a bundle of fibers crossing the midline (represented in gray).

Differential diagnosis
Isolated agenesis of the corpus callosum may be confused with moderate hydrocephaly. In hydrocephaly, one of the clues that differentiate this disorder from ACC is the presence of the cavum septum pellucidum.

Associated anomalies
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.4,6-7 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.8 Extracranial malformations include abnormalities of the face and of the cardiovascular, genitourinary, gastrointestinal, respiratory, and musculoskeletal systems.6,9-11

Associated genetic syndromes
Over 175 genetic syndromes may present partial or total agenesis of the corpus callosum, with different etiologies, including inborn errors of metabolism, chromosome and Mendelian disorders. These diseases are associated with specific malformations that allow a precise differential diagnosis in the majority of the cases: Aicardi, Andermann, Acrocalosal, FG, Naiman & Fraser, Ziegler, Menkes, Dogan, Shapira & Cohen, Cao, Lynn, Kaplan, Wilson, Pineda, Young.12

Prognosis
Prognosis is dependent upon the cause of the malformation. In approximately 90% of the cases of isolated ACC, development is normal. ACC can even be an occasional finding in the investigation of children with mental retardation or microcephaly.11

Genetic counseling
Agenesis of the corpus callosum is one of the most common brain malformations observed in humans. It is a heterogeneous malformation, with many etiologies. The recurrence risk of ACC, whether it is isolated or in addition to inborn errors of metabolism or genetic syndromes, depends on the underlying cause. If ACC is associated with aneuploidy the recurrence risk is 1% or the maternal-age related risk for aneuploidy, whichever is greater. Isolated ACC with no known cause is usually sporadic but familial cases have been reported and the recurrence risk is probably on the order of 2 to 3%.12 ACC is a known criterion for the diagnosis of certain syndromes, such as Aicardi, Andermann, and acrocallosal syndromes. Prenatal counseling for fetal agenesis of the corpus callosum is difficult as the prognosis is uncertain. The association with other cerebral abnormalities increases the likelihood of a poor outcome but ultrasonographic assessment of the fetal brain is limited and magnetic resonance imaging evaluation might be necessary.14

Treatment
There is no treatment for this condition

Support groups,  parent"s & patient"s web pages

ACC Network & ACC-Listserv E-Mail Support Group

mailto:UM-ACC@maine.maine.edu

Parent"s web pages

References

1..Pilu G, Nicolaides KH. Diagnosis of Fetal Abnormalities. The 18-23 week scan. London: Parthenon Publishing;1999:9-10.
2..Freytag E, Lindenberg R. Neuropathologic findings in patients in a hospital for the mentally deficient: a survey of 359 cases. Jhon Hopkins Med J 1967;121:379-392
3.. Grogono JL. Children with agenesis of the corpus callosum. Dev Med Child Neurol 1968;10:613-20
4.. Jeret JS, Serur D, Wisniewski K, et al. Clinicopathological findings associated with agenesis of the corpus callosum. Brain Dev 1987;9:255-60
5.. Rakic P, Yakovlev PI. Development of the corpus callosum and cavum septi in man. J Comp Neurol 1968;132:45-72.
6. Parrish ML, Roessmann U, Levinshon MW. Agenesis of the corpus callosum: a study of the frequency of associated malformations. Ann Neurol 1979;6:349-354.
7. Dobyns WB. Agenesis of the corpus callosum and gyral malformations are frequent manifestations of nonketotic hyperglycinemia. Neurology 1989;39:817-820.
8.Barkovitch AJ, Norman D. Anomalies of the corpus callosum: correlation with further anomalies of the brain. AJR AM J Roentgenol 1988;151:171-179.
9. Franco I, Kogan S, Fisher J, et al. Genitourinary malformations associated with agenesis of the corpus callosum. J Urol 1993;149:1119-1121.
10.Kozlowski K, Ouvrier RA. Agenesis of the corpus callosum with mental retardation and osseous lesions. Am J Med Genet 1993;48:6-9.
11. Lyn G. Congenital malformations of the brain. In: Levene MI, Lilford RJ, Bennet MJ, Punt J. Fetal and Neonatal Neurology and Neurosurgery. London: Churchill Livingstone; 1995:196-7.
12. Young ID. Genetics of neurodevelpmental abnormalities. In: Levene MI, Lilford RJ, Bennet MJ, Punt J. Fetal and Neonatal Neurology and Neurosurgery. London: Curchill Livingstone; 1995:256.
13. Philip N, Chabrol B, Lethel V. Genetics of agenesis of the corpus callosum. Neurochirurgie 1998;44(1Suppl):99-101.
14.d´Ercole C, Girard N, Carvello L, et al. Prenatal diagnosis of fetal corpus callosum agenesis by ultrasonography and magnetic resonance imaging. Prenat Diagn 1998;18(3):247-53.