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A newborn has hypotonia and abnormal eye movements. Brain MRI reveals the characteristic "molar tooth sign" at the midbrain-hindbrain junction.

AR; ciliopathy (>40 genes including AHI1, CEP290, CC2D2A, TMEM67)

  • "Molar tooth sign" on axial MRI (hypoplastic cerebellar vermis, elongated superior cerebellar peduncles)
  • Hypotonia, ataxia
  • Abnormal breathing patterns (episodic hyperpnea)
  • Abnormal eye movements (oculomotor apraxia)
  • Variable: retinal dystrophy, kidney disease (nephronophthisis), liver fibrosis
  • Diagnosis requires the "molar tooth sign" on axial brain MRI plus hypotonia and developmental delay/intellectual disability
  • Confirm with molecular testing via a multigene ciliopathy panel (>40 genes including AHI1, CEP290, CC2D2A, TMEM67); CEP290 correlates with retinal disease and TMEM67 with liver fibrosis
  • Evaluate for organ involvement at diagnosis: dilated eye exam/electroretinogram, renal ultrasound and function, and liver function/ultrasound
  • Supportive multidisciplinary care: physical, occupational, and speech therapy plus developmental and educational support
  • Monitor for and manage the episodic breathing abnormalities (especially in infancy), feeding difficulties, and seizures
  • Periodic surveillance for progressive retinal dystrophy, nephronophthisis/renal failure, and hepatic fibrosis; ophthalmology, nephrology, and hepatology follow-up

"JOUBERT": Tell a "Cili (silly) Joke" (ciliopathy), One extra digit (polydactyly), Under 70 IQ, Brain anomalies (molar tooth sign on axial MRI), Eye anomalies, Renal failure / Retina, Tone is low (hypotonia leading to ataxia)

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