Joubert Syndrome

Main Features

  • Cerebellar vermis hypoplasia or aplasia
  • episodic tachypnea (“panting like a dog”) and apnea in infancy
  • jerky eye movements, hypotonia, developmental delay

Eye Findings

  • Ocular Motor Abnormalities
    • Oculomotor Apraxia
      • inability to voluntarily initiate saccades and compensate by using head thrusts.
    • Absent smooth pursuit
    • Hypometric saccades with prolonged latency; they change direction of fixation by turning their heads
    • Nystagmus – pendular, rotary, horizontal, see-saw, torsional
    • Supranuclear Ocular motor palsies
    • Strabismus (up to 80%)
      • Horizontal (esotropia or exotropia) or vertical
  • Congenital Retinal Dystrophy (30%)
    • Progressive chorioretinal pigmentary changes including reports of “mottling” in periphery
    • Attenuation of retinal arterioles
    • Nonrecordable / attenuated ERG, but Preserved flash and pattern VEPs (Differentiates from LCA)
    • Rod photoreceptors are more severely affected than cones
    • May have good Best Corrected Visual Acuity – reports of 20/40 (also better than LCA)
    • Those with Retinal dystrophy also have Renal cysts and other kidney disease
  • Ptosis – Bilateral or Unilateral
  • Chorioretinal coloboma 17%-30%
  • Optic Nerve coloboma.

Differentiating Joubert’s from Leber’s Congenital Amaurosis

  • Both have nonrecordable or severely attenuated ERG, but Joubert’s has recordable (less than normal) flash and pattern VEPs
  • Joubert’s generally has better Visual acuity

Etiology

  • Defects in function of primary cilia, one of the ciliopathies
  • Mostly Autosomal Recessive
    • Half the cases have a mutation in only one of 4 genes: AHI1 15%, C5orf42 13%, KIAA0586 11% and CSPP1 10%
    • at least 28 genes implicated most related to cilia formation/function
  • First described in 1969, by 1991, 94 patients reported
  • More commonly reported in cultures of consanguinity, although distributed worldwide

Other Findings

  • Neuro: Mental retardation, ataxia
  • Respiratory: Episodic tachypnea and apnea that improves with age
  • Renal: Renal cysts, inflammation, sclerosis, can be deadly
  • GI: protruding tongue, tongue tumors, pyloric stenosis, duodenal atresia, hepatic inflammation
  • Bone: Polydactyly

References