Agenesis of the Corpus Callosum

Q04.0

Holoprosencephaly, agenesis of septum pelludicum

0.3-0.7 % in the general population¹ and 2-3% in the developmentally disabled.²

Variable. Environmental factors (alcohol, maternal phenylketonuria, infections and ischemia)^{3, 4} and genetic factors.⁵

Agenesis may be complete or partial, and is usually associated with significant distortion of cerebral anatomy. With complete absence of the corpus callosum the cavum septi pellucidi is not formed and the posterior portion of lateral ventricles is frequently enlarged.⁶ The third ventricle may be displaced superiorly and a cyst or a lipoma may be formed in the interhemispheric fissure. The medial cerebral sulci form a radiate pattern around the third ventricle. The pericallosal artery does not develop and branches of the anterior cerebral artery ascend vertically.⁷ With partial agenesis, the posterior portion is missing to varying degrees. Modifications of the cerebral anatomy similar to those found with the complete variety are encountered but to a lesse degree. The anterior portion of the cavum septi pellucidi is usually present. Hypoplasia of the corpus callosum refers to a corpus callosum that has a normal length but is thinner than normal.

Even in expert hands the diagnosis is difficult prior to 18 weeks gestation. The complete variety is identified by demonstrating the absence of the complex formed by the corpus callosum and cavum septum pellucidum in sagittal or coronal planes. Axial planes usually do not allow a certain diagnosis, but they usually reveal important clues including absence of the cavum septi pellucidi, ventriculomegaly,8-10disproportionate enlagement of the posterior portion of the ventricles (colpocephaly) with a teardrop configuration of the lateral ventricles⁷, upward displacement of the third ventricle⁷, and abnormal midline lesions, including cysts¹¹ and lipomas.^{7, 12} Partial agenesis of the corpus callosum affects the most posterior portion and is usually associated with a lesser degree of distortion of intracranial anatomy. The diagnosis is difficult as it requires demonstration of a foreshortened corpus callosum with a midsagittal view.^{7, 13} Color and power Doppler may facilitate the diagnosis of agenesis of the corpus callosumbe helpful. The pericallosal artery, a branch of the anterior callosal artery, normally runs along the superior surface of the corpus callosum in a semicircular loop. When the corpus callosum is absent the loop is lost⁷ while with partial agenesis is much shortened.

Axial views do not allow visualization of the normal corpus callosum and therefore it is not surprising that diagnosis of agenesis is difficult in low risk patients.¹⁴

Three-dimensional ultrasound may be useful allowing a reconstruction of a sagittal plane even in cases where this is not easily accessible directly.^{15, 16} Some authors recommend use of MR^17-19 In our experience, ultrasound is effective in diagnosing both complete and partial agenesis, but we agree that MR may be more informative regarding the presence of associated anomalies and cortical malformations in particular.^{17, 18} Hpoplasia of the corpus callosum has rarely been diagnosed in utero.

Ventriculomegaly conditions with midline fluid-filled lesions (arachnoid cyst, porencephaly or an aneurysm of the vein of Galen).

In pediatric series neural anomalies occur in 85% of the cases and extra-CNS anomalies in 62%.²¹ Cardiovascular anomalies mainly include cono-truncal malformations such as tetralogy of Fallot and double outlet right ventricle. Agenesis of the corpus callosum is a part of Mendelian syndromes.(Table 1) Chromosomal anomalies (trisomy 18, trisomy 8 and trisomy 13) occur in 20% of cases.²² In prenatal series the cerebral malformations most frequently reported include Dandy-Walker malformation, cortical malformations and interhemispheric cysts.¹¹

Associated malformations are frequently present and have a major impact on the pregnosis. Isolated non-syndromic ACC is associated with a normal to borderline intellectual development in about 70% of cases but a progressive decrease in intellectual capacity throughout the years has been documented and most infants have significant difficulties in school.

Exclusion of associated anomalies. In continuing pregnancies no modification of standard obstetric management is required.

5% when syndromes are excluded.

1. Grogono JL. Children with agenesis of the corpus callosum. Dev Med Child Neurol1968 Oct;10(5):613-6.

2. Jeret JS, Serur D, Wisniewski K, Fisch C. Frequency of agenesis of the corpus callosum in the developmentally disabled population as determined by computerized tomography. Pediatr Neurosci1985-1986;12(2):101-3.

3. Malinger G, Lev D, Zahalka N, Ben Aroia Z, Watemberg N, Kidron D, et al. Fetal cytomegalovirus infection of the brain: the spectrum of sonographic findings. AJNR Am J Neuroradiol2003 Jan;24(1):28-32.

4. Weinstein AS, Goldstein RB, Barkovich AJ. In utero disappearance of the corpus callosum secondary to extensive brain injury. J Ultrasound Med2003;22(8):837-40.

5. 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 A2008 Oct 1;146A(19):2501-11.

6. Barkovich AJ, Norman D. Anomalies of the corpus callosum: correlation with further anomalies of the brain. AJR Am J Roentgenol1988 Jul;151(1):171-9.

7. Pilu G, Sandri F, Perolo A, Pittalis MC, Grisolia G, Cocchi G, et al. Sonography of fetal agenesis of the corpus callosum: a survey of 35 cases. Ultrasound Obstet Gynecol1993 Sep 1;3(5):318-29.

8. Filly RA, Cardoza JD, Goldstein RB, Barkovich AJ. Detection of fetal central nervous system anomalies: a practical level of effort for a routine sonogram. Radiology1989 Aug;172(2):403-8.

9. Patel MD, Filly AL, Hersh DR, Goldstein RB. Isolated mild fetal cerebral ventriculomegaly: clinical course and outcome. Radiology1994 Sep;192(3):759-64.

10. Goldstein RB, La Pidus AS, Filly RA, Cardoza J. Mild lateral cerebral ventricular dilatation in utero: clinical significance and prognosis. Radiology1990 Jul;176(1):237-42.

11. Barkovich AJ, Simon EM, Walsh CA. Callosal agenesis with cyst: a better understanding and new classification. Neurology2001 Jan 23;56(2):220-7.

12. Mulligan G, Meier P. Lipoma and agenesis of the corpus callosum with associated choroid plexus lipomas. In utero diagnosis. J Ultrasound Med1989 Oct;8(10):583-8.

13. Volpe P, Paladini D, Resta M, Stanziano A, Salvatore M, Quarantelli M, et al. Characteristics, associations and outcome of partial agenesis of the corpus callosum in the fetus. Ultrasound Obstet Gynecol2006 May;27(5):509-16.

14. Bennett GL, Bromley B, Benacerraf BR. Agenesis of the corpus callosum: prenatal detection usually is not possible before 22 weeks of gestation. Radiology1996 May;199(2):447-50.

15. Pilu G, Ghi T, Carletti A, Segata M, Perolo A, Rizzo N. Three-dimensional ultrasound examination of the fetal central nervous system. Ultrasound Obstet Gynecol2007 Aug;30(2):233-45.

16. Pilu G, Segata M, Ghi T, Carletti A, Perolo A, Santini D, et al. Diagnosis of midline anomalies of the fetal brain with the three-dimensional median view. Ultrasound Obstet Gynecol2006 May;27(5):522-9.

17. Benacerraf BR, Shipp TD, Bromley B, Levine D. What does magnetic resonance imaging add to the prenatal sonographic diagnosis of ventriculomegaly? J Ultrasound Med2007 Nov;26(11):1513-22.

18. Levine D, Barnes PD. Cortical maturation in normal and abnormal fetuses as assessed with prenatal MR imaging. Radiology1999 Mar;210(3):751-8.

19. Levine D, Barnes PD, Madsen JR, Li W, Edelman RR. Fetal central nervous system anomalies: MR imaging augments sonographic diagnosis. Radiology1997 Sep;204(3):635-42.

20. Pilu G, Falco P, Perolo A, Sandri F, Cocchi G, Ancora G, et al. Differential diagnosis and outcome of fetal intracranial hypoechoic lesions: report of 21 cases. Ultrasound Obstet Gynecol1997 Apr;9(4):229-36.

21. Parrish ML, Roessmann U, Levinsohn MW. Agenesis of the corpus callosum: a study of the frequency of associated malformations. Ann Neurol1979 Oct;6(4):349-54.

22. Serur D, Jeret JS, Wisniewski K. Agenesis of the corpus callosum: clinical, neuroradiological and cytogenetic studies. Neuropediatrics1988 May;19(2):87-91.

23. Paul LK, Brown WS, Adolphs R, Tyszka JM, Richards LJ, Mukherjee P, et al. Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nat Rev Neurosci2007;8(4):287-99.

24. Byrd SE, Radkowski MA, Flannery A, McLone DG. The clinical and radiological evaluation of absence of the corpus callosum. Eur J Radiol1990 Jan-Feb;10(1):65-73.

25. Gupta JK, Lilford RJ. Assessment and management of fetal agenesis of the corpus callosum. Prenat Diagn1995 Apr;15(4):301-12.

26. Moutard ML, Kieffer V, Feingold J, Kieffer F, Lewin F, Adamsbaum C, et al. Agenesis of corpus callosum: prenatal diagnosis and prognosis. Childs Nerv Syst2003 Aug;19(7-8):471-6.

27. Young ID, Trounce JQ, Levene MI, Fitzsimmons JS, Moore JR. Agenesis of the corpus callosum and macrocephaly in siblings. Clin Genet1985 Sep;28(3):225-30

Table 1. Syndromes featuring agenesis of the corpus callosum.

Frequent in:

Acrocallosal syndrome (AR)

Aicardi syndrome (X-linked dominant)

Andermann syndrome (AR)

Cerebro-oculo-facio-skeletal (COFS) syndrome (AR)

Fryns syndrome (AR)

Marden-Walker syndrome(AR)

Meckel Gruber syndrome (AR)

Microphtalmia-linear skin defects syndrome (X-linked dominant)

Miller Diexer syndrome (lissencephaly syndrome)

Neu-Laxova syndrome(AR)

Septo-Optic dysplasia sequence

Walker-Warburg syndrome (X-linked dominant)

Zellweger syndrome (AR)

Occasional in:

Apert syndrome (AR)

Baller-Gerold syndrome (AR)

Calloso-genital dysplasia syndrome (AR)

Coffin-Siris syndrome (?AR)

Congenital microgastria-limb reduction complex (unknown)

Crouzon syndrome (AD)

Duplication 4p syndrome

Fetal alcohol syndrome

Fetal warfarin syndrome

FG syndrome (X-linked recessive)

Fronto-nasal dysplasia sequence (sporadic/AD)

Gorlin syndrome (AD)

Greig cephalopolysyndactyly syndrome (AD)

Hydrolethalus syndrome(AR, X-linked dominant)

Lens dysplasia (X-linked recessive)

Marshall-Smith syndrome (unknown)

Oculo-auricolo-vertebral spectrum (unknown)

Oculo-cerebro-cutaneous syndrome (Delleman syndrome) (unknown)

Opitz syndrome (AD, X-linked recessive)

Oral-facio-digital syndrome type 1 (X-linked dominant)

Peters?-Plus syndrome (AR)

Radial aplasia-thrombocytopenia syndrome (AR)

Rubinstein ?Taybi syndrome 8SPORADIC)

Shapiro syndrome (X-linked recessive)

Simpson-Golabi-Behmel syndrome (X-linked recessive)

Trisomy 8 syndrome

Trisomy 13 syndrome

Trisomy 18 syndrome

X-linked hydrocephalus spectrum (X-linked recessive)

XO syndrome

XXXXY syndrome (hypoplastic)

Yunis-Varon syndrome

Metabolic disorders

AR, AD autosomal recessive, autosomal dominant

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