Leber Congenital Amaurosis 10 and Other CEP290-Related Ciliopathies (CEP290)
CEP290-related ciliopathies include four different overlapping disorders, known as Leber congenital amaurosis, Bardet-Biedl syndrome, Joubert syndrome and Meckel syndrome. All diseases are inherited in an autosomal recessive manner and are can be caused by pathogenic variants in the gene CEP290. Leber congenital amaurosis manifests with vision loss at birth or in early infancy. Patients have profound loss of vision at an early age, and some have been reported to have intellectual disability. Bardet-Biedl syndrome is characterized by obesity, intellectual disability, kidney disease, and loss of vision beginning with loss of night vision and progression to tunnel vision and blindness. 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. 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; it is not reduced in patients with Leber congenital amaurosis, but death in infancy is expected in patients with Meckel syndrome. Currently, it is not possible to predict which phenotype a patient will have based on the variants inherited.
For information about carrier frequency and residual risk, please see the residual risk table.