Agenesis of Corpus Callosum (ACC)
Agenesis of the corpus callosum (ACC) is a congenital malformation where the nerve fibres connecting the two cerebral hemispheres are either partially or completely absent.
It is one of the most common congenital brain malformations. The severity and clinical presentation are highly variable, ranging from asymptomatic to severe neurological impairment, and often depend on the presence of other associated brain or systemic abnormalities.
Pathophysiology and Clinical Presentation
ACC results from a disruption of brain development between the 12th and 20th weeks of gestation. The exact cause is often unknown, but it can be associated with:
Genetic factors: Chromosomal abnormalities (e.g., trisomy 13, 18), specific genetic syndromes (e.g., Aicardi syndrome), or monogenic mutations.
Prenatal insults: Infections, ischaemia, or exposure to teratogens like alcohol (fetal alcohol syndrome).
Clinical features in children are diverse and can include:
Neurological: Seizures, motor coordination difficulties (especially with bimanual tasks), and developmental delays (motor, language, and cognitive).
Behavioural/Cognitive: Learning disabilities, problems with abstract reasoning, social communication deficits (which may overlap with autism spectrum disorder), and difficulty with social cues like sarcasm.
Physical: In some syndromic cases, other abnormalities like hydrocephalus, midline facial defects, or eye and ear irregularities may be present.
Diagnosis and Management in the UK
Diagnosis is often made prenatally via foetal ultrasound or MRI, or postnatally by cranial MRI. An MRI is crucial for a definitive diagnosis and to identify any associated brain malformations. A full paediatric workup should include:
Clinical examination: To assess for developmental milestones, hypotonia, and dysmorphic features.
Genetic testing: A chromosomal microarray or whole-exome sequencing is increasingly recommended to identify an underlying genetic cause, which can help determine prognosis and recurrence risk for the family.
Imaging: A paediatric neurologist will confirm the diagnosis and rule out other conditions such as holoprosencephaly.
Management is symptom-based and multidisciplinary. There is no cure for ACC itself. Key components of care include:
Early Intervention: Referral to early intervention services is critical to support development.
Multidisciplinary Team: The care team should include a paediatric neurologist, developmental paediatrician, physiotherapist, occupational therapist, and a speech and language therapist.
Symptom Management: Medication may be needed for seizures, and educational support (e.g., an Individual Education Plan) is often necessary for learning difficulties.
Recent Developments and Research
Recent research has shed light on the functional reorganisation of the brain and the underlying causes of ACC:
Brain Plasticity: Studies using functional MRI have shown that the brain can adapt, with neural pathways rerouting to compensate for the missing corpus callosum. The presence of Probst bundles (aberrant fibres that fail to cross the midline) has been associated with better adaptive and social outcomes, suggesting a compensatory role.
Social Cognition: Research from institutions like Caltech and the International Research Consortium for the Corpus Callosum and Cerebral Connectivity (IRC5) has further defined the “core syndrome” of ACC, particularly highlighting social vulnerabilities. Studies have shown that individuals with ACC may have difficulty with emotion recognition and tend to avoid eye contact, a pattern also seen in some forms of autism. This has led to a greater understanding of the role of specific neurons (e.g., von Economo neurons) in social and emotional processing.
Genetic Discoveries: Advances in genetic sequencing have identified an increasing number of genes and syndromes linked to ACC. This provides more accurate prognostic information and allows for better genetic counselling for families.