Normal Cognitive Functions in Joubert Syndrome

Abstract

Developmental delay and subsequent impaired cognitive functions are present in almost all patients with Joubert syndrome (JS). We report on a 20-year-old woman with mild clinical signs of JS (minimal truncal ataxia and oculomotor apraxia) but typical molar tooth sign on neuroimaging, normal full scale (IQ=93), verbal (IQ=93), and performance intelligence quotient (IQ=94). Only minor difficulties in visual-spatial organization and in some executive functions could be detected. This pattern of deficits is partly reminiscent of the cerebellar cognitive affective syndrome. Her diagnosis was only reached following the diagnosis of JS in two brothers with severe cognitive impairment. Molecular investigations demonstrated a homozygous mutation in the INPP5E gene. This exceptional observation confirms that normal cognitive functions are possible in JS and corroborates the well known intrafamilial variability.

Joubert syndrome - cognition - cerebellar cognitive affective syndrome

References

• 1 Baker K, Beales PL. Making sense of cilia in disease: the human ciliopathies.  Am J Med Genet C Semin Med Genet. 2009;  151C 281-295
• 2 Bielas S, Silhavy JL, Brancati F. et al . Mutations in the inositol polyphosphate-5-phosphatase E gene links phosphatidyl inositol signaling to the ciliopathies.  Nat Genet. 2009;  41 1032-1036
• 3 Bolduc ME, Limperopoulos C. Neurodevelopmental outcomes in children with cerebellar malformations: a systematic review.  Dev Med Child Neurol. 2009;  51 256-267
• 4 Coene KL, Roepman R, Doherty D. et al . OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin.  Am J Hum Genet. 2009;  85 465-481
• 5 Doherty D. Joubert syndrome: insights into brain development, cilium biology, and complex disease.  Semin Pediatr Neurol. 2009;  16 143-154
• 6 Edvardson S, Shaag A, Zenvirt S. et al . Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation.  Am J Hum Genet. 2010;  86 93-97
• 7 Fennell EB, Gitten JC, Dede DE. et al . Cognition, behavior, and development in Joubert syndrome.  J Child Neurol. 1999;  14 592-596
• 8 Gitten J, Dede D, Fennell E. et al . Neurobehavioral development in Joubert syndrome.  J Child Neurol. 1998;  13 391-397
• 9 Gunay-Aygun M, Parisi MA, Doherty D. et al . MKS3-related ciliopathy with features of autosomal recessive polycystic kidney disease, nephronopththisis, and Joubert syndrome.  J Pediatr. 2009;  155 386-392
• 10 Hodgkins PR, Harris CM, Shawkat FS. et al . Joubert syndrome: long-term follow-up.  Dev Med Child Neurol. 2004;  46 694-699
• 11 Kumandas S, Akcakus M, Coskun A. et al . Joubert syndrome: review and report of seven new cases.  Eur J Neurol. 2004;  11 505-510
• 12 Maria BL, Quisling RG, Rosainz LC. et al . Molar tooth sign in Joubert syndrome: clinical, radiologic, and pathologic significance.  J Child Neurol. 1999;  14 368-376
• 13 Parisi MA. Clinical and molecular features of Joubert syndrome and related disorders.  Am J Med Genet C Semin Med Genet. 2009;  151C 326-340
• 14 Riva D, Giorgi C. The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours.  Brain. 2000;  123 1051-1061
• 15 Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome.  Brain. 1998;  121 561-579
• 16 Steinlin M, Schmid M, Landau K. et al . Follow-up in children with Joubert syndrome.  Neuropediatrics. 1997;  28 204-211
• 17 Tavano A, Grasso R, Gagliardi C. et al . Disorders of cognitive and affective development in cerebellar malformations.  Brain. 2007;  130 2646-2660
• 18 Tavano A, Borgatti R. Evidence for a link among cognition, language and emotion in cerebellar malformations.  Cortex. 2009;  Sep 16 epub
• 19 Ziegler AL, Deonna T, Calame A. Hidden intelligence of a multiply handicapped child with Joubert syndrome.  Dev Med Child Neurol. 1990;  32 261-266

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