RPGRIP1L-associated ciliopathies include three overlapping disorders, known as Joubert syndrome, COACH syndrome, and Meckel syndrome. All diseases are inherited in an autosomal recessive manner and are can be caused by pathogenic variants in the gene RPGRIP1L. Clinical features of Joubert syndrome include intellectual disability, brain malformations, ocular problems including uncontrollable eye movements and loss of vision, and kidney cysts leading to end-stage renal disease. COACH syndrome has many of the same features as Joubert syndrome, with the addition of liver fibrosis that is present at birth. Meckel syndrome often manifests before birth and is characterized by occipital encephalocele, brain malformations, facial dysmorphism, renal agenesis, and extra digits. Life expectancy varies according to the phenotype; most patients with Joubert syndrome are expected to have a normal life expectancy, but Meckel syndrome is usually lethal in infancy. Pathogenic variants that result in no residual protein are more likely to be associated with Meckel syndrome.
For information about carrier frequency and residual risk, please see the residual risk table.