Joubert Syndrome 6

Alternative Names

  • JBTS6
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

610688

Mode of Inheritance

Autosomal recessive

Gene Map Locus

8q22.1

Description

Joubert syndrome is a phenotypically heterogeneous ciliopathy classically defined by brain anomalies such as cerebellar vermian 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.  JBTS6 also results in neurological problems such as delayed psychomotor development, intellectual disability, ataxia and hypotonia.  Other symptoms include breathing dysregulation, renal defects such as nephronophthisis, microcysts and renal failure, liver abnormalities such as hepatic fibrosis and bile duct proliferation, and ophthalmological impairments such as oculomotor apraxia, chorioretinal coloboma and blindness.

The disorder follows an autosomal recessive pattern of inheritance and is caused by mutations in the TMEM67 gene.  This gene encodes a ciliary transmembrane protein believed to be involved in ciliogenesis and signaling.  Both homozygous and compound heterozygous mutations in the TMEM67 gene are associated with JBTS6.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
610688.1Saudi ArabiaFemaleYes Global developmental delay; Hearing impa...NM_153704.6:c.2707G>CHomozygousAutosomal, RecessiveMaddirevula et al. 2018
610688.2Saudi ArabiaMaleYes Global developmental delay; Generalized ...NM_153704.6:c.739C>GHomozygousAutosomal, RecessiveMaddirevula et al. 2018
610688.3.1United Arab EmiratesMaleYesYes Blake's pouch cyst; Generalized hypotoni...NM_153704.5:c.725A>GHomozygousAutosomal, RecessiveHafeez et al. 2020 Patient has a simila...

Other Reports

Saudi Arabia

Al-Hamed et al. (2016) examined a cohort of 44 Saudi families affected by antenatal cystic kidney disease.  In one consanguineous family, the fetus showed enlarged echogenic kidneys with cysts, oligohydramnios/anhydramnios and growth malformations such as a narrow thorax and dolichocephaly.  The case resulted in fetal death.  The fetus was found to be homozygous for the novel TMEM67 mutation c. 457T>G (p.C153G).  The mutation was predicted to be disease causing and occurred at a highly conserved residue.  In another consanguineous family, antenatal ultrasound of the proband found enlarged cystic kidneys, oligohydramnios/anhydramnios, cerebellar vermis aplasia, hydrocephalus, congenital heart malformation and pericardial effusion.  This case also resulted in fetal death.  The proband had two similarly affected siblings and was homozygous for the novel TMEM67 splice site mutation c.1413-2A>G.  This mutation also occurred at a highly conserved residue and was predicted to result in a broken acceptor site. 

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