What are the causes of Vermian syndromes?

Causes of Vermian Syndromes

Vermian syndromes are primarily caused by genetic mutations, congenital infections, vascular disruptions, and metabolic disorders that affect cerebellar vermis development, with genetic causes being the most common etiology.

Genetic Causes

Genetic etiologies represent the most significant cause of vermian syndromes, with several specific genetic abnormalities identified:

• Tubulinopathies: Mutations in genes encoding microtubule components (TUBB) and associated proteins (KATNB1, CENPJ) can cause vermian hypoplasia 1
• Dystroglycanopathies: Autosomal recessive disorders affecting O-glycosylation of α-dystroglycan, often presenting with vermian hypoplasia and eye involvement 1
• Ciliopathies: Including Joubert syndrome and related disorders
• Chromosomal abnormalities:
  • Trisomy 18 (Edwards syndrome) - associated with vermian hypoplasia 1
  • 22q11.2 deletion syndrome - can present with vermian abnormalities 1
• Single gene disorders:
  • GPSM2 mutations (Chudley–McCullough syndrome) - associated with mesial parasagittal vermian abnormalities 1
  • EML1 mutations - linked to ribbon-like heterotopia with vermian agenesis 1
  • LAMA2 mutations - can cause limited cobblestone cortex with vermian abnormalities 1
  • DIS3L2 mutations (Perlman syndrome) - associated with vermian abnormalities 1

Vascular Causes

Vascular disruptions represent another important cause of vermian syndromes:

• Arteriovenous malformations (AVMs) of the cerebellar vermis - can present with intracranial hemorrhage (73% of cases) and recurrent bleeding (60% of cases) 2
• Vascular disruptive events during pregnancy - can lead to vermian abnormalities 1
• Twin-to-twin transfusion syndrome - particularly affects the donor twin 1
• Death of a monozygotic co-twin - associated with vermian malformations 1

Congenital Infections

Several congenital infections can cause vermian abnormalities:

• Cytomegalovirus (CMV) - accounts for 12-30% of cases of polymicrogyria which can include vermian involvement 1
• Toxoplasmosis - associated with vermian hypoplasia 1
• Syphilis - can cause cerebellar vermian abnormalities 1
• Varicella zoster virus - linked to vermian malformations 1
• Zika virus - associated with cerebellar vermian abnormalities 1

Metabolic Disorders

Metabolic conditions can also affect the cerebellar vermis:

• Peroxisomal disorders:
  • Zellweger syndrome - presents with vermian abnormalities 1
  • D-bifunctional protein deficiency - shows vermian involvement in up to 65% of patients 1

Syndromic Associations

Several syndromes include vermian abnormalities as a key feature:

• Neurocutaneous disorders:
  • Neurocutaneous melanosis - associated with inferior vermian hypoplasia 3
  • Neurofibromatosis type 1 - can present with vermian abnormalities 1
• Occipital encephalocele with tecto-cerebellar dysraphia - characterized by aplasia of the vermis and deformity of the tectum 4
• Colobomatous microphthalmia with microcephaly - associated with marked cerebellar and vermian hypoplasia 5
• Marfan syndrome - can present with vermian abnormalities 6

Clinical Manifestations

Vermian syndromes typically manifest with:

• Truncal ataxia - characteristic of cerebellar vermian pathology 1
• Postural instability - impaired balance with increased sway path length 7
• Tremor - particularly in the 2-5 Hz band 7
• Developmental delay - common in congenital vermian abnormalities 1
• Ocular abnormalities - including nystagmus and other eye movement disorders 1

Diagnostic Approach

When evaluating a patient with suspected vermian syndrome:

1. Brain MRI - gold standard for evaluating vermian abnormalities, showing superior soft tissue contrast 1
2. Genetic testing - including chromosomal microarray analysis and next-generation sequencing 1
3. Infectious disease workup - including PCR for CMV and other congenital infections 1
4. Metabolic screening - particularly very long chain fatty acids (VLCFAs) for peroxisomal disorders 1

Key Considerations

• Vermian syndromes often present with multisystem involvement, requiring comprehensive evaluation
• The pattern of vermian abnormality (complete vs. partial, superior vs. inferior) can help narrow the differential diagnosis
• Early diagnosis is critical for appropriate management and genetic counseling
• Neuroimaging findings should be correlated with clinical presentation and genetic testing results for accurate diagnosis