Clinical Characteristics

Molar tooth sign
Caused by a specific constellation of mid and hindbrain malformations, e.g. cerebellar vermis hypoplasia, thick and abnormally oriented superior cerebellar peduncles, and unusually deep interpeduncular fossa. These are also associated with defective decussation of the superior cerebellar peduncles. Cerebellar vermis hypoplasia in JS is thought to be a result of reduced proliferation and migration of germinal zone granular cell precursors; which later develop into granule neurons that don’t align in a typical manner due variations in signalling. The symptoms associated with the syndrome include dysmorphic features (prominent forehead, upturned nose, and open mouth) and neurological symptoms (hypotonia, ataxia, developmental delay, intellectual disability, and abnormal ocular movements). During the neonatal period, patients can have an altered respiratory pattern with episodes of apnoea and hyperpnoea.

Renal disease
Affects ~25% of patients with JSRD. This often presents as structural tubule-intestinal disease with irregular, thickened basal membrane or a tubular epithelium, progressive interstitial fibrosis, and small cysts at the corticomedullary junction. The renal component of JSRD manifests as a juvenile-onset cystic kidney disease, nephronophthisis, progressing to end-stage kidney disease.

Retinal disease
Retinitis pigmentosa-like retinal degeneration is often associated in JSRD. Thinning of the retinal layers causes night blindness and can lead to severe vision loss.