Healthcare recommendations for Joubert syndrome

Abstract

Joubert syndrome (JS) is a recessive neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation recognizable on axial brain magnetic resonance imaging as the "Molar Tooth Sign". Although defined by the neurological features, JS is associated with clinical features affecting many other organ systems, particularly progressive involvement of the retina, kidney, and liver. JS is a rare condition; therefore, many affected individuals may not have easy access to subspecialty providers familiar with JS (e.g., geneticists, neurologists, developmental pediatricians, ophthalmologists, nephrologists, hepatologists, psychiatrists, therapists, and educators). Expert recommendations can enable practitioners of all types to provide quality care to individuals with JS and know when to refer for subspecialty care. This need will only increase as precision treatments targeting specific genetic causes of JS emerge. The goal of these recommendations is to provide a resource for general practitioners, subspecialists, and families to maximize the health of individuals with JS throughout the lifespan.

Keywords: Joubert syndrome; ciliopathy; kidney; liver; retina; treatment.

FIGURE 1

Diagnostic features of Joubert syndrome on magnetic resonance imaging (MRI). (a) molar tooth sign (MTS) on T2-weighted axial images due to the combination of long, thick superior cerebellar peduncles (the roots of the tooth) and a deep interpeduncular fossa (the cutting surface of the tooth). This appearance is not always captured in a single plane, so it is important to evaluate the MRI as a whole rather than relying on a single image. (b) Superior cerebellar foliar dysplasia (bracket) on axial T2-weighted images, sometimes seen in the absence of the MTS in individuals carrying pathogenic variants in the JS-associated genes (note that the folia at this level are usually shaped like a U or V). (c) Horizontally oriented superior cerebellar peduncle (white arrowhead) on T1-weighted parasagittal image; (d) Vermis hypoplasia (outline), elevated roof of the fourth ventricle, and rostrally displaced fastigium on T1-weighted sagittal image; (e) Long, thick superior cerebellar peduncles (black arrowhead) T2-weighted coronal image; (f) Appearance of a cerebellar cleft (black arrow indicating fluid at the cerebellar midline) on T2-weighted coronal image. (a'-f') similar images from an unaffected individual of the same age