Joubert syndrome is an autosomal recessive disorder presenting with psychomotor delay, hypotonia, ataxia, oculomotor apraxia, and neonatal breathing abnormalities. Neuroradiologically, Joubert syndrome is characterized by a peculiar malformation of the midbrain-hindbrain junction known as the 'molar tooth sign' (MTS) consisting of cerebellar vermis hypoplasia or aplasia, thick and maloriented superior cerebellar peduncles, and abnormally deep interpeduncular fossa.
The JBTS5 phenotype is mainly characterized by the neurologic and neuroradiologic features of Joubert syndrome associated with severe retinal and renal involvement. In addition, JBTS5 presents a broad clinical spectrum including incomplete phenotypes such as cerebelloretinal and cerebellorenal syndromes. The full-blown JBTS5 phenotype largely overlaps that of Senior-Loken syndrome (SLSN), which is characterized by retinitis pigmentosa plus juvenile nephronophthisis and is attributable to mutations in genes associated with nephronophthisis and encoding ciliary proteins.
Al-Hamed et al. (2016) aimed to understand the genetic causes of antenatal cystic kidney disease by studying a cohort of 44 families and analyzing DNA extracted from chorionic villus sampling, amniotic fluid, placental blood or peripheral blood cells. In one family, the antenatal ultrasound examination revealed cystic kidneys and cerebellar vermis aplasia. DNA analysis found a homozygous known mutation c.5668G>T (p.G1890*) in the CEP290 gene. The authors noted that the affected patient was alive at 6 months of age. In another family, antenatal ultrasound found only cystic kidneys with no other symptoms. The case resulted in fetal death and no DNA was available for genetic analysis. However, both the parents were found to be heterozygous for a novel CEP290 mutation c.3777_3778delAG (p.R1259Sfs*16). The symptoms and mutations in both cases were indicative of Joubert syndrome 5.
Valente et al. (2006) performed direct sequencing of CEP290 gene in 18 consanguineous JSRD families. Independent homozygous nucleotide changes were identified; including three nonsense mutations (c.4732G>T, c.5668G>T and c.5824C>T), one 1-bp deletion (c.3176delT) and one missense mutation (c.21G>T). JSRD patients who have CEP290 mutations suffered from neurological and neuroradiological features associated with severe retinal and renal involvement.