Overview
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Joubert Syndrome (JS) and Related Disorders (JSRD) are a group of ciliopathies characterized by mid-hindbrain malformation, developmental delay, hypotonia, oculomotor apraxia and breathing abnormalities. Cilia play a crucial role in appropriate axonal growth and connectivity which are essential for functional wiring of the brain. The classic midbrain-hindbrain malformation is a hallmark image finding known as molar tooth sign. Joubert Syndrome and Related Disorders are a group of clinically and genetically heterogeneous disorders involving ciliopathy-related genes. Therefore, clinical manifestations have multiorgan involvement, mainly retinal dystrophy, hepatic fibrosis and polydactyly, among others. With the exception of rare X-linked recessive cases, Joubert Syndrome and Related Disorders follow an autosomal recessive inheritance pattern.
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The Igenomix Joubert Syndrome and Related Disorders Precision Panel can serve as a screening and diagnostic tool ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
- The Igenomix Joubert Syndrome and Related Disorders Precision Panel is indicated for those patients with clinical and/or imaging findings suggestive of Joubert Syndrome and Related Disorders presenting with the following manifestations:
- Hypotonia
- Developmental delay
- Ataxia
- Abnormal eye and tongue movements
- Respiratory control disturbances
- Cleft lip or palate
- Seizures
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment involving a multidisciplinary team focusing on respiratory and feeding problems in neonates and infants. Cognitive and behavioral assessments with adequate neuropsychological rehabilitation.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
- Identification of molecular defect in couples at risk allowing prenatal genetic tasting where neuroimaging may be uninformative early in the pregnancy.
References
Valente EM, Dallapiccola B, Bertini E. Joubert syndrome and related disorders. Handb Clin Neurol. 2013;113:1879-88. doi: 10.1016/B978-0-444-59565-2.00058-7. PMID: 23622411.
Parisi, M., & Glass, I. (2003). Joubert Syndrome. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.
Radha Rama Devi, A., Naushad, S. M., & Lingappa, L. (2020). Clinical and Molecular Diagnosis of Joubert Syndrome and Related Disorders. Pediatric neurology, 106, 43–49. https://doi.org/10.1016/j.pediatrneurol.2020.01.012
Brancati, F., Dallapiccola, B., & Valente, E. M. (2010). Joubert Syndrome and related disorders. Orphanet journal of rare diseases, 5, 20. https://doi.org/10.1186/1750-1172-5-20
Guo, J., Otis, J. M., Suciu, S. K., Catalano, C., Xing, L., Constable, S., Wachten, D., Gupton, S., Lee, J., Lee, A., Blackley, K. H., Ptacek, T., Simon, J. M., Schurmans, S., Stuber, G. D., Caspary, T., & Anton, E. S. (2019). Primary Cilia Signaling Promotes Axonal Tract Development and Is Disrupted in Joubert Syndrome-Related Disorders Models. Developmental cell, 51(6), 759–774.e5. https://doi.org/10.1016/j.devcel.2019.11.005
Bachmann-Gagescu, R., Dempsey, J. C., Phelps, I. G., O’Roak, B. J., Knutzen, D. M., Rue, T. C., Ishak, G. E., Isabella, C. R., Gorden, N., Adkins, J., Boyle, E. A., de Lacy, N., O’Day, D., Alswaid, A., Ramadevi A, R., Lingappa, L., Lourenço, C., Martorell, L., Garcia-Cazorla, À., Ozyürek, H., … Doherty, D. (2015). Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. Journal of medical genetics, 52(8), 514–522. https://doi.org/10.1136/jmedgenet-2015-103087