Keywords
Ataxia
Ciliopathies
Cerebellar diseases
Hypotonia
How to Cite
Abstract
Introduction. Joubert syndrome is a ciliopathy characterized by the presence of the molar tooth sign in magnetic resonance imaging or computed tomography. The classic involvement consists of hypotonia, neurodevelopmental delay, ataxia, oculomotor apraxia and abnormal respiratory pattern.
Development. Described for the first time in 1969, the spectrum of Joubert syndrome has expanded in recent decades based on the next-generation sequencing techniques and improvements in neuroimaging techniques. The clinical manifestations are very heterogeneous, even within the same genotype and family, and in most of the patients, neurological symptoms are combined with multisystem involvement on various levels. Diagnosis is clinical-radiological, with genetic confirmation. There is no specific treatment, and management is often complex and involves several different specialists. Conclusions. Joubert syndrome is an underdiagnosed entity, and knowledge of its clinical and radiological manifestations is essential to detect cases. The role of genetic diagnosis is key in order to offer advice to families, as well as to guide the possible evolution in certain genotypes. When it is being managed within the clinical practice, a multidisciplinary approach is necessary to approach the different areas in which these patients may present health problems.
References
Romani M, Micalizzi A, Valente EM. Joubert syndrome: con- genital cerebellar ataxia with the molar tooth. Lancet Neurol. 2013; 12(9): 894-905. https://doi.org/10.1016/S1474-4422(13)70136-4
Joubert syndrome: MedlinePlus Genetics [Internet]. Medline- Plus. [citado 20 de junio de 2023]. Disponible en: https:// medlineplus.gov/genetics/condition/joubert-syndrome/
Raynes HR, Shanske A, Goldberg S, Burde R, Rapin I. Joubert syndrome: Monozygotic twins with discordant phenotypes. J Child Neurol. 1999; 14(10): 649-54. https://doi.org/10.1177/088307389901401005
O'Neill MJF, McKusick VA. Joubert syndrome 1; JBTS1 [Inter- net]. OMIM.org. 2021 [citado 20 de junio de 2023]. Disponible en: https://www.omim.org/entry/213300
Gana S, Serpieri V, Valente EM. Genotype-phenotype correlates in Joubert syndrome: A review. Am J Med Genet C Semin Med Genet. 2022; 190(1): 72-88. https://doi.org/10.1002/ajmg.c.31963
Joubert M, Eisenring JJ, Preston J, Andermann F. Familial agenesis of the cerebellar vermis: A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology. 1969; 19(9): 813-25. https://doi.org/10.1212/WNL.19.9.813
Maria BL, Quisling RG, Rosainz LC, Yachnis AT, Gitten J, Dede D, et al. Molar tooth sign in Joubert syndrome: clinical, radiolo- gic, and pathologic significance. J Child Neurol. 1999; 14(6): 368-76. https://doi.org/10.1177/088307389901400605
Parisi MA. The molecular genetics of Joubert syndrome and related ciliopathies: The challenges of genetic and phenotypic heterogeneity. Transl Sci Rare Dis. 2019; 4(1-2): 25-49. https://doi.org/10.3233/TRD-190041
Wallace SE, Bean LJ. Resources for Genetics Professionals - Genetic disorders associated with founder variants common in the Hutterite population [Internet]. GeneReviews® [Internet]. University of Washington, Seattle; 2020 [citado 20 de junio de 2023]. Disponible en: https://www.ncbi.nlm.nih.gov/books/ NBK556767/
Ferland RJ, Eyaid W, Collura RV, Tully LD, Hill RS, Al-Nouri D, et al. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nat Genet. 2004; 36(9): 1008-13. https://doi.org/10.1038/ng1419
Radha Rama Devi A, Naushad SM, Lingappa L. Clinical and molecular diagnosis of Joubert Syndrome and related disorders. Pediatr Neurol. 2020; 106: 43-9. https://doi.org/10.1016/j.pediatrneurol.2020.01.012
Phelps IG, Dempsey JC, Grout ME, Isabella CR, Tully HM, Doher- ty D, et al. Interpreting the clinical significance of combined variants in multiple recessive disease genes: Systematic investi- gation of Joubert Syndrome yields little support for oligogenicity. Genet Med Off J Am Coll Med Genet. 2018; 20(2): 223-33. https://doi.org/10.1038/gim.2017.94
Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, et al. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell. 2012; 150(3): 533-48.
Yachnis AT, Rorke LB. Neuropathology of Joubert syndrome. J Child Neurol. 1999; 14(10): 655-9. https://doi.org/10.1177/088307389901401006
Maria BL, Hoang KB, Tusa RJ, Mancuso AA, Hamed LM, Quis- ling RG, et al. «Joubert syndrome» revisited: key ocular motor signs with magnetic resonance imaging correlation. J Child Neurol. 1997; 12(7): 423-30. https://doi.org/10.1177/088307389701200703
Braddock SR, Henley KM, Maria BL. The face of Joubert syn- drome: A study of dysmorphology and anthropometry. Am J Med Genet A. 2007; 143A(24): 3235-42. https://doi.org/10.1002/ajmg.a.32099
Gunny RS. Paediatric Neuroradiology. En: Adam A, Dixon AK, Gillard JH, Goh V, Grainger AJ, Jäger R, et al., editores. Grain- ger & Allison's Diagnostic Radiology [Internet]. 7th ed. Polonia: Elsevier; 2021 [citado 3 de abril de 2022]. p. 1984-2045. Disponible en: https://www.clinicalkey.es/#!/content/book/3- s2.0-B9780702075247000768?scrollTo=%23hl0001214
Poretti A, Dietrich Alber F, Brancati F, Dallapiccola B, Valente EM, Boltshauser E. Normal cognitive functions in joubert syn- drome. Neuropediatrics. 2009; 40(6): 287-90. https://doi.org/10.1055/s-0030-1249630
Bulgheroni S, D'Arrigo S, Signorini S, Briguglio M, Di Sabato ML, Casarano M, et al. Cognitive, adaptive, and behavioral fea- tures in Joubert syndrome. Am J Med Genet A. 2016; 170(12): 3115-24. https://doi.org/10.1002/ajmg.a.37938
Hodgkins PR, Harris CM, Shawkat FS, Thompson DA, Chong K, Timms C, et al. Joubert syndrome: long-term follow-up. Dev Med Child Neurol. 2004; 46(10): 694-9. https://doi.org/10.1111/j.1469-8749.2004.tb00983.x
Lamônica DAC, Ribeiro C da C, Richieri-Costa A, Giacheti CM. Language, behavior and neurodevelopment in Joubert syndrome: a case report. CoDAS. d2016; 28(6): 823-7. https://doi.org/10.1590/2317-1782/20162015184
Parisi M, Glass I. Joubert Syndrome [Internet]. GeneReviews® [Internet]. University of Washington, Seattle; 2017 [citado 26 de abril de 2022]. Disponible en: https://www.ncbi.nlm.nih. gov/books/NBK1325/
Braddock BA, Farmer JE, Deidrick KM, Iverson JM, Maria BL. Oromotor and communication findings in joubert syndrome: further evidence of multisystem apraxia. J Child Neurol. 2006; 21(2): 160-3. https://doi.org/10.1177/08830738060210020501
Farmer JE, Deidrick KM, Gitten JC, Fennell EB, Maria BL. Parenting stress and its relationship to the behavior of children with Joubert syndrome. J Child Neurol. 2006; 21(2): 163-7. https://doi.org/10.1177/08830738060210020401
Poretti A, Snow J, Summers AC, Tekes A, Huisman TAGM, Aygun N, et al. Joubert syndrome: neuroimaging findings in 110 patients in correlation with cognitive function and genetic cause. J Med Genet. 2017; 54(8): 521-9. https://doi.org/10.1136/jmedgenet-2016-104425
Bachmann-Gagescu R, Dempsey JC, Bulgheroni S, Chen ML, D'Arrigo S, Glass IA, et al. Healthcare recommendations for Joubert syndrome. Am J Med Genet A. 2020; 182(1): 229-49. https://doi.org/10.1002/ajmg.a.61399
Poretti A, Christen HJ, Elton LE, Baumgartner M, Korenke GC, Sukhudyan B, et al. Horizontal head titubation in infants with Joubert syndrome: a new finding. Dev Med Child Neurol. 2014; 56(10): 1016-20. https://doi.org/10.1111/dmcn.12489
Wolfe L, Lakadamyali H, Mutlu GM. Joubert syndrome associa- ted with severe central sleep apnea. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2010; 6(4): 384-8. https://doi.org/10.5664/jcsm.27882
Dempsey JC, Phelps IG, Bachmann-Gagescu R, Glass IA, Tully HM, Doherty D. Mortality in Joubert syndrome. Am J Med Genet 2017; 173(5): 1237-42. https://doi.org/10.1002/ajmg.a.38158
Hannah WB, DeBrosse S, Kinghorn B, Strausbaugh S, Aitken ML, Rosenfeld M, et al. The expanding phenotype of OFD1- related disorders: Hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia. Mol Genet Genomic Med. 2019; 7(9): e911. https://doi.org/10.1002/mgg3.911
Stephen J, Vilboux T, Mian L, Kuptanon C, Sinclair CM, Yildi- rimli D, et al. Mutations in KIAA0753 cause Joubert syndrome associated with growth hormone deficiency. Hum Genet. 2017; 136(4): 399-408. https://doi.org/10.1007/s00439-017-1765-z
Doherty D. Joubert syndrome: insights into brain development, cilium biology and complex disease. Semin Pediatr Neurol. 2009; 16(3): 143-54. https://doi.org/10.1016/j.spen.2009.06.002
Doherty D, Parisi MA, Finn LS, Gunay-Aygun M, Al-Mateen M, Bates D, et al. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis). J Med Genet. 2010; 47(1): 8-21. https://doi.org/10.1136/jmg.2009.067249
Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman Gers- tein M, Piwnica-Worms K, Choyke P, et al. Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology. 2013; 144(1): 112-121.e2. https://doi.org/10.1053/j.gastro.2012.09.056
Vilboux T, Doherty DA, Glass IA, Parisi MA, Phelps IG, Cullinane AR, et al. Molecular genetic findings and clinical correlations in 100 patients with Joubert syndrome and related disorders prospectively evaluated at a single center. Genet Med Off J Am Coll Med Genet. 2017; 19(8): 875-82. https://doi.org/10.1038/gim.2016.204
Strongin A, Heller T, Doherty D, Glass IA, Parisi MA, Bryant J, et al. Characteristics of liver disease in 100 individuals with Joubert syndrome prospectively evaluated at a single center. J Pediatr Gastroenterol Nutr. 2018; 66(3): 428-35. https://doi.org/10.1097/MPG.0000000000001816
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