Normal Vermis Development

  • Vermis grows rostro-caudally, covering the 4th ventricle:
    • Usually complete by 18 weeks gestation.
    • May continue developing up to 24 weeks gestation.

Clinical Significance of Gestational Age at Diagnosis

  • Vermian hypoplasia identified before 24 weeks:
    • Approximately 50% resolve by term (Patek et al. 2012).
  • Vermian hypoplasia diagnosed after 24 weeks:
    • Nearly always confirmed postnatally.

Inferior Vermian Hypoplasia

  • Traditionally thought to result from delayed or incomplete formation of inferior vermis lobules.
  • Classic definition:
    • Shortened rostro-caudal (longitudinal) vermian diameter.
    • Anterior:Posterior lobe ratio < 1:2.
  • Recent insights challenge this view:
    • Inferior lobules actually form first.
    • Hypoplasia likely results from failure of posterior lobe growth (neovermis), located caudal to the primary fissure.
    • Therefore, arrested downward vermian growth due to neovermis hypoplasia is common.
  • Diagnostic caution:
    • Clear distinction of vermian lobules is difficult by fetal MRI, especially before late gestation.
    • Diagnosis of "inferior vermian hypoplasia" should be reserved for clear cases demonstrated by detailed imaging.

Syndromic Vermian Hypoplasia: Joubert Syndrome and Related Disorders (JSRD)

Molar Tooth Malformation ("Molar Tooth Sign")

  • Key radiologic feature of Joubert syndrome and related disorders.
  • Consists of:
    • Elongated, thick, horizontally-oriented superior cerebellar peduncles.
    • Deep interpeduncular fossa.
    • Vermian hypo/dysplasia.
    • Variable cerebellar hemispheric involvement.
  • Additional brain abnormalities occur in ~30%:
    • Brainstem anomalies.
    • Supratentorial malformations.
  • Axonal guidance defects commonly seen:
    • Affects superior cerebellar peduncles and corticospinal tracts.
    • 90% have normal corpus callosum.

Genetics and Clinical Variability of Joubert Syndrome

  • Joubert syndrome and related disorders (JSRD):
    • Group of autosomal recessive ciliopathies.
    • 27 genes identified to date.
    • Genes primarily involved with endothelial cilia function.
  • Clinical features:
    • Neonatal respiratory disturbances (episodic hyperpnea).
    • Cerebellar ataxia.
    • Eye movement abnormalities (ocular motor apraxia).
    • Intellectual disability.
    • Retinopathy (typically mild).
    • Progressive nephropathy (kidney involvement).
    • Hepatic dysfunction.

Joubert Syndrome and Related Disorders (JSRD) Spectrum

DisorderClinical Features
Joubert Syndrome (Classic) Neonatal respiratory hyperpnea, ocular motor abnormalities, vermian hypoplasia (molar tooth sign), mild retinopathy, renal disease, intellectual disability, ataxia.
COACH Syndrome Cerebellar vermis hypoplasia, Oligophrenia (intellectual disability), Ataxia, ocular Coloboma, Hepatic fibrosis.
CORS (Cerebello-Oculo-Renal Syndrome) Vermis hypoplasia, congenital blindness, severe renal disease (renal failure).
Oro-Facial-Digital Syndrome (type IV) Vermis hypoplasia, oral-facial abnormalities (cleft lip/palate, tongue tumors, notched lip), digital anomalies (polydactyly, bifid digits).

Clinical Implications and Management

  • Diagnosis essential for prognosis, genetic counseling, and multidisciplinary management.
  • Management is largely supportive:
    • Address neurological, developmental, visual, renal, and hepatic complications.
    • Genetic counseling crucial due to autosomal recessive inheritance.