Joubert Syndrome 9

Alternative Names

  • JBTS9
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

612285

Mode of Inheritance

Autosomal recessive

Gene Map Locus

4p15.32

Description

Joubert syndrome 9 is a multisystem disorder characterized by brain anomalies such as cerebellar vermis hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa.  These findings give the appearance of a molar tooth sign on a brain MRI.  Symptoms of JBTS9 may include neurological problems such as intellectual disability, seizures and ventriculomegaly, ophthalmological anomalies such as retinitis pigmentosa, astigmatism, nystagmus and cataract as well as renal and hepatic abnormalities such as nephronophthisis and hepatosplenomegaly.

JBTS9 follows an autosomal recessive pattern of inheritance.  It is caused by mutations in the CC2D2A  gene, which encodes a ciliary protein that helps prevent the diffusion of transmembrane proteins between the cilia and plasma membranes.  The CC2D2A protein is also predicted to be involved in primary cilium assembly, determination of left/right symmetry and embryonic brain development.  Mutations in this gene associated with JBTS9 usually include homozygous and compound heterozygous transitions and indels.  Interestingly, digenic inheritance has also been seen in this disorder; some Joubert syndrome patients have been reported to carry a heterozygous mutation in the CC2D2A  gene along with a heterozygous mutation in the CEP41  gene.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
612285.1Saudi ArabiaMaleYes Breathing dysregulation; Generalized hyp...NM_001378615.1:c.3364C>THomozygousAutosomal, RecessiveMaddirevula et al. 2018
612285.2Saudi ArabiaMaleYesYes Hydrocephalus; Failure to thrive; Renal ...NM_001378615.1:c.3364C>THomozygousAutosomal, RecessiveMaddirevula et al. 2018
612285.3United Arab EmiratesUnknownYes Ataxia; Global developmental delay; Hypo...NM_001378615.1:c.4583G>ACompound heterozygousAutosomal, RecessiveBen-Salem et al. 2014 Patient from 'MTI-12...

Other Reports

Saudi Arabia

Al-Hamed et al. (2016) attempted to identify causal gene mutations in a cohort of 44 Saudi families affected by antenatal cystic kidney disease.  In one case, antenatal ultrasound examination found cystic kidneys, cerebellar vermis aplasia, dilated cisterna magna and corpus callosum agenesis.  The subject was found to be homozygous for the known CC2D2A mutation c.3364C>T (p.P11225).  In another case, ultrasound findings included cystic kidneys, cerebellar vermis aplasia and dilated cisterna magna.  While fetal DNA was unavailable for analysis, both parents were found to be heterozygous for the known CC2D2A mutation c.3084delG (p.R1028Rfs*3).  The cases were indicative of Joubert syndrome 9 and both resulted in fetal death. 

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