Vermian Agenesis: Definition and Clinical Significance
Vermian agenesis is a congenital brain malformation characterized by the complete or partial absence of the cerebellar vermis—the midline structure connecting the two cerebellar hemispheres—which typically manifests with truncal ataxia, oculomotor dysfunction, and developmental delays. 1, 2
Anatomic and Imaging Features
The cerebellar vermis is the midline portion of the cerebellum that connects the two hemispheres. When absent or underdeveloped, characteristic MRI findings include:
- Absence or severe hypoplasia of the posterior lobe of the vermis 2
- Hypoplasia of the anterior lobe 2
- A narrow sagittal cleft separating the cerebellar hemispheres, creating what is described as a "buttocks sign" 2
- Fourth ventricle deformity due to the absence of the normal vermian tissue 2
In some cases, vermian agenesis occurs with fusion of the cerebellar hemispheres (rhombencephalosynapsis), representing a distinct and rare variant of this malformation 3, 4.
Clinical Manifestations
Truncal ataxia is the hallmark clinical feature, as the cerebellar vermis specifically controls midline balance and truncal stability 1. Additional neurological findings include:
- Complex oculomotor dysfunction (abnormal eye movements, nystagmus) 2
- Developmental delays and intellectual disability 2, 5
- Gait abnormalities and postural instability 1
Notably, respiratory symptoms are typically absent in isolated vermian agenesis without posterior fossa cysts 2, which helps distinguish this from other posterior fossa malformations.
Associated Malformations and Syndromes
Vermian agenesis rarely occurs in isolation and is frequently accompanied by other brain abnormalities that significantly impact prognosis:
- Cortical developmental abnormalities: microcephaly with simplified gyral patterns, lissencephaly (particularly with TUBA1A mutations), polymicrogyria, and cobblestone malformations 6
- Corpus callosum abnormalities: hypoplasia or agenesis frequently accompanies vermian hypoplasia 6, 7
- Septo-optic dysplasia: absence of septum pellucidum with optic nerve hypoplasia 3
- Posterior fossa cysts: some cases present with Dandy-Walker-like malformations, though this represents a different pathological spectrum 4, 8
Genetic syndromes associated with vermian agenesis include:
- TUBA1A mutations (with dysmorphic basal ganglia and brainstem) 6
- DYNC1H1 variants (with large caudate nuclei) 6
- Fetal Alcohol Spectrum Disorders 6
- Familial forms with autosomal recessive inheritance 5
Diagnostic Evaluation
Brain MRI with diffusion-weighted imaging is the gold standard to characterize the specific pattern of vermian absence and identify associated malformations 7. Morphometric analysis is essential, as visual assessment alone may miss subtle abnormalities 7.
Chromosomal microarray analysis should be performed as first-tier genomic testing 6. If lissencephaly is present on imaging, test for chromosome 17p13.3 microdeletion (LIS1 locus) first, as this is the most common genetic cause 6, 7.
Management and Multidisciplinary Care
The American Academy of Pediatrics recommends establishing baseline developmental assessment in all children with confirmed vermian hypoplasia or agenesis, regardless of whether additional anomalies are present, with reassessment at regular intervals to detect emerging delays 6. Early intervention services should be initiated immediately upon identification of any developmental delays 7.
Required Specialty Evaluations:
- Ophthalmologic evaluation: screen for ptosis, amblyopia, refractive errors, and strabismus 6, 7
- Audiologic assessment: sensorineural hearing loss occurs in up to 40% of syndromic cases 6, 7
- Cardiology evaluation: required before any surgical intervention in suspected genetic syndromes, as structural cardiac defects are common 6, 7
- Renal ultrasound: screen for structural anomalies in syndromic presentations 6, 7
Designating a primary care medical home is essential to coordinate preventive care, immunizations, and acute illness management while neurology manages malformation-specific complications 6, 7. A portable medical summary should be created including diagnosis, current medications, emergency management plan, and all provider contact information 7.
Prognosis and Prognostic Factors
The prognosis varies significantly based on whether vermian agenesis occurs in isolation or with associated brain malformations. The presence of additional cortical developmental abnormalities, corpus callosum anomalies, or genetic syndromes substantially worsens developmental outcomes 6. Isolated vermian agenesis without other structural brain abnormalities generally has a better prognosis, though developmental delays and ataxia remain common 2.