Agenesis of the Corpus Callosum
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Agenesis of the corpus callosum (ACC) is complete or partial absence of the structure that connects the two hemispheres of the brain - the corpus callosum, which is the largest fibre tract in the central nervous system.[1]It can occur as an isolated condition or in combination with other cerebral abnormalities. These include:
- Arnold-Chiari malformation.
- Dandy-Walker syndrome.
- Andermann's syndrome.
- Schizencephaly (clefts or deep divisions in brain tissue).
- Holoprosencephaly (failure of the forebrain to divide into lobes).
Aicardi's syndrome is found in girls alone - see below under heading of that name.
ACC can also be associated with problems in other parts of the body - eg, midline facial defects. There is a spectrum of disability ranging from subtle to severe depending on associated brain abnormalities. Intelligence may be normal with mild compromise of skills requiring matching of visual patterns. But children with the most severe brain malformations may have low intelligence quotient (IQ), seizures, hydrocephalus and spasticity.
Epidemiology
It is one of the most frequent malformations in the brain with a reported incidence ranging between 0.5 and 70 in 10,000 births.[2]
Pathogenesis
Formation of the corpus callosum begins as early as six weeks of gestation, with the first fibres crossing the midline at 11-12 weeks of gestation. The basic shape is completed by 18-20 weeks of gestation.
As yet unknown factors cause disruption to development of the fetal brain between the 3rd and 12th week of pregnancy. Potential causes may include chromosome errors, inherited genetic factors, prenatal infections or injuries, prenatal toxic exposures, structural blockage by cysts or other brain abnormalities and metabolic disorders.[3]
Presentation
There is a wide spectrum of clinical presentation.[4, 5]Those presentations most common to most children with callosal abnormalities include:[6]
- Vision impairment.
- Hypotonia.
- Poor motor co-ordination.
- Delays in motor milestones.
- Low perception of pain.
- Delayed toilet training.
- Early feeding/chewing and swallowing difficulties.
- Seizures.
- Spasticity.
- Gastro-oesophageal reflux.
- Hearing impairments.
- Abnormal head and facial features.
- Learning difficulties.
Some children have cognitive disabilities (difficulty in complex problem solving) and social difficulties (missing subtle social cues), even when their IQ is normal. This has been found to be due to abnormal face processing and may lead to confusion with autistic spectrum disorders.
Aicardi's syndrome
Aicardi's syndrome is a rare genetic condition with probably only 300-500 cases worldwide. It is characterised by:[7]
- Complete or partial absence of the corpus callosum.
- Chorioretinal lacunae.
- Severe seizures.
Nearly all children with Aicardi's syndrome have severe learning difficulties:
- Most have no expressive language and remain totally dependent.
- A few have some understanding of language, can walk with support or independently and are fairly responsive to the environment.
Also:
- Self-harm and aggression towards people and objects have been reported and may be involuntary.
- Disturbed sleep and waking in the night are common and possibly due to fitting. An electroencephalogram (EEG) may show the characteristic pattern of hypsarrhythmia - sometimes called West's syndrome.[8]
- MRI scan or CT scan of the head will help demonstrate the loss of neural tissue.
The outcome of Aicardi's syndrome is severe, with a high early mortality, considerable morbidity and a generally poor developmental outcome.[9]
Investigations
Structural brain abnormalities are diagnosed by MRI or CT scan, prenatal ultrasound, or prenatal MRI.[10]
Management
There are no specific treatments for ACC but most patients will require input from a multidisciplinary team. This may include neurologists, neuropsychologists, occupational therapists, physiotherapists, speech and language therapists, paediatricians, geneticists, specific schooling support and early intervention specialists.
Prognosis
Prognosis depends on the extent and severity of malformations.[11] It is not possible for the corpus callosum to regenerate or degenerate.
Although some individuals with callosal disorders have average intelligence and lead normal lives, neuropsychological testing reveals subtle differences in higher cortical function compared with individuals of the same age and education without ACC.
Further reading and references
Chiappedi M, Bejor M; Corpus callosum agenesis and rehabilitative treatment. Ital J Pediatr. 2010 Sep 1736:64. doi: 10.1186/1824-7288-36-64.
Agenesis of corpus callosum; Online Mendelian Inheritance in Man (OMIM)
O'Driscoll MC, Black GC, Clayton-Smith J, et al; Identification of genomic loci contributing to agenesis of the corpus callosum. Am J Med Genet A. 2010 Sep152A(9):2145-59.
Santo S, D'Antonio F, Homfray T, et al; Counseling in fetal medicine: agenesis of the corpus callosum. Ultrasound Obstet Gynecol. 2012 Nov40(5):513-21. doi: 10.1002/uog.12315.
Chiappedi M, Fresca A, Baschenis IM; Complete corpus callosum agenesis: can it be mild? Case Rep Pediatr. 20122012:752751. doi: 10.1155/2012/752751. Epub 2012 Aug 29.
Bedeschi MF, Bonaglia MC, Grasso R, et al; Agenesis of the corpus callosum: clinical and genetic study in 63 young patients. Pediatr Neurol. 2006 Mar34(3):186-93.
Lund C, Bjornvold M, Tuft M, et al; Aicardi Syndrome: An Epidemiologic and Clinical Study in Norway. Pediatr Neurol. 2014 Oct 31. pii: S0887-8994(14)00653-5. doi: 10.1016/j.pediatrneurol.2014.10.022.
Taghdiri MM, Nemati H; Infantile spasm: a review article. Iran J Child Neurol. 2014 Summer8(3):1-5.
Aicardi J; Aicardi syndrome. Brain Dev. 2005 Apr27(3):164-71.
Ozyuncu O, Yazicioglu A, Turgal M; Antenatal diagnosis and outcome of agenesis of corpus callosum: A retrospective review of 33 cases. J Turk Ger Gynecol Assoc. 2014 Mar 115(1):18-21. doi: 10.5152/jtgga.2014.84666. eCollection 2014.
Schell-Apacik CC, Wagner K, Bihler M, et al; Agenesis and dysgenesis of the corpus callosum: clinical, genetic and Am J Med Genet A. 2008 Oct 1146A(19):2501-11.