The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome-related disorders

Dev Med Child Neurol. 2011 Sep;53(9):793-798. doi: 10.1111/j.1469-8749.2011.04021.x. Epub 2011 Jun 17.


A group of disorders with disparate symptomatology, including congenital cerebellar ataxia, retinal blindness, liver fibrosis, polycystic kidney disease, and polydactyly, have recently been united under a single disease mechanism called 'ciliopathies'. The ciliopathies are due to defects of the cellular antenna known as the primary cilium, a microtubule-based extension of cellular membranes found in nearly all cell types. Key among these ciliopathies is Joubert syndrome, displaying ataxia, oculomotor apraxia, and mental retardation* with a pathognomonic 'molar tooth sign' on brain magnetic resonance imaging. The importance of ciliary function in neuronal development has been appreciated only in the last decade with the classification of Joubert syndrome as a ciliopathy. This, together with the identification of many of the clinical features of ciliopathies in individuals with Joubert syndrome and the localization of Joubert syndrome's causative gene products at or near the primary cilium, have defined a new class of neurological disease. Cilia are involved in diverse cellular processes including protein trafficking, photoreception, embryonic axis patterning, and cell cycle regulation. Ciliary dysfunction can affect a single tissue or manifest as multi-organ involvement. Ciliary defects have been described in retinopathies such as retinitis pigmentosa and Leber congenital amaurosis (defects in photoreceptor ciliary protein complexes), renal syndromes with nephronophthisis and cystic dysplastic kidneys, and liver conditions such as fibrosis and biliary cirrhosis. Recognizing the diverse presentations of the ciliopathies and screening strategies following diagnosis is an important part of the treatment plan of children with cilia-related disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apraxias / congenital
  • Bardet-Biedl Syndrome
  • Cerebellar Diseases / classification
  • Cerebellar Diseases / complications*
  • Cerebellar Diseases / pathology*
  • Cilia / pathology*
  • Ciliary Motility Disorders
  • Cogan Syndrome
  • Eye Abnormalities
  • Humans
  • Leber Congenital Amaurosis
  • Magnetic Resonance Imaging
  • Orofaciodigital Syndromes

Supplementary concepts

  • Apraxia, oculomotor, Cogan type
  • Orofaciodigital syndrome 6