Joubert syndrome with oculorenal defect

Joubert syndrome with oculorenal defect is a rare subtype of Joubert syndrome and related disorders that affects the brain, kidneys, and eyes. It is associated with pathogenic variants in several genes, including TMEM216, CEP290, CC2D2A, TMEM237, and TMEM138, which play important roles in cellular development and signaling. Typically, affected children present in early life with neurological and multi-system manifestations. This condition is extremely rare, affecting fewer than 1 in a million individuals.

The clinical presentation is marked by a constellation of neurological, renal, and ocular features. Almost universally, individuals exhibit the molar tooth sign on brain MRI and cerebellar vermis hypoplasia, which are characteristic diagnostic clues. Renal manifestations include stage 5 chronic kidney disease, renal corticomedullary cysts, polyuria, and renal sodium wasting, while ocular involvement may include ptosis, chorioretinal coloboma, retinal dystrophy, and optic atrophy. In addition, nearly all affected individuals experience profound global developmental delay and severe intellectual disability, along with hypotonia and anemia. Not all individuals experience all features, and severity varies considerably.

Joubert syndrome with oculorenal defect results from pathogenic variants in genes such as TMEM216, CEP290, CC2D2A, TMEM237, and TMEM138. These genes are essential for normal brain, kidney, and eye development, and disruptions interfere with cellular signaling and structural integrity. The condition is inherited in an autosomal recessive manner, meaning that a child must inherit two altered copies of the gene, one from each parent. It is more common when parents share a common ancestor, as both may carry the same rare genetic variant, and genetic counseling is recommended for families to discuss recurrence risks.

Currently, management of Joubert syndrome with oculorenal defect focuses on supportive care and individualized symptom management, as there are no approved treatments specific to this condition. Care is provided by a multidisciplinary team to address the complex neurological, renal, and ocular issues. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Genetic counseling is recommended to help families understand the condition and discuss family planning options, and treatment strategies are tailored based on the patient’s specific needs.

Joubert syndrome with oculorenal defect is a lifelong condition, with outcomes that vary widely between individuals. With current standards of care, many individuals benefit from early intervention and continuous multidisciplinary management, although challenges related to kidney function, vision, and cognitive development persist. Outcomes described in medical literature continue to evolve as standards of care improve, and the course of the condition may include periods of stability interspersed with complications. Families are encouraged to connect with specialists and support groups to obtain up-to-date information and guidance for ongoing management.

A few clinical trials are currently underway exploring new treatment approaches for Joubert syndrome with oculorenal defect. Individuals interested in learning more about these investigational therapies can search ClinicalTrials.gov or discuss potential eligibility with their care team.