CASE 15048 Published on 11.11.2017

Joubert syndrome



Case Type

Clinical Cases


Donato Angel, MD. Marco L. Charry, MD.

Hospital Militar Central.
Bogotá, Colombia.

14 years, female

Area of Interest Neuroradiology brain ; Imaging Technique MR
Clinical History
Sisters of 14 and 7 years of age born from consanguine parents with no history of the disease in their family.
They present with delayed motor and language development, horizontal pendular nystagmus and strabismus, facial dysmorphism with forehead prominence, deep set eyes, and bilateral epicanthic folds.
Imaging Findings
Brain MRIs show hypoplasia of the vermis with prominent straight cerebellar peduncles giving it the classic appearance of the “molar tooth” sign. A deepened interpeduncular fossa is also noted. The posterior fossa shows the fourth ventricle with a “bat wing” morphology and dysplasia of the cerebellar cortex.
Joubert syndrome (JS) is an autosomal or X- linked recessive condition characterised by abnormal eye movements, respiratory control disturbances, hypotonia, ataxia and intellectual disability of variable severity. [1] The hallmark feature of JS is a distinctive midbrain and hindbrain malformation known as the ‘molar tooth sign’ (MTS) on axial brain MRI or CT. This radiological feature reflects thickened and horizontally oriented superior cerebellar peduncles, hypoplasia of the cerebellar vermis, and a deep interpeduncular fossa [2]. In association with the MTS, also the ‘Bat wing’ appearance of the fourth ventricle, cerebellar cortical dysplasia, abnormalities of the nuclei of the pons, cerebellum, and medulla can be found. Decussation of the corticospinal and superior cerebellar and abnormal activation patterns during motor tasks are absent [3, 4, 5]. Marie Joubert et al. first described JS in 1969 in four siblings, and one sporadic case that exhibited rapid episodic breathing, abnormal eye movements, ataxia and mental retardation with agenesis of the cerebellar vermis in a large French-Canadian family with consanguinity traced back 11 generations to a common ancestor [2, 5]. The term "JS and related disorders" (JSRD) refers to a group of disorders presenting with JS in association with multiple systemic abnormalities, such as retinal dystrophy, renal cystic dysplasia, juvenile nephronophthisis, hepatic involvement and skeletal findings such as cone-shaped epiphyses and polydactyly [2]. For other authors, JS is classified into two types depending on the presence or absence of retinal dystrophy. Type 1 without retinal dysplasia and Type 2 with retinal dysplasia. [6] The pathogenetic basis of this disorder is related to the dysfunction of a subcellular organelle, the primary cilium, making JS part of the group of disorders termed “ciliopathies.” Ciliopathies are an extensive group of autosomal recessive or X-linked disorders caused by defects of the primary cilium, a highly conserved organelle intracellular found in most vertebrate cell types. [1] The primary cilium is a non-motile organelle from the surface of nearly all cell types, it works as a sensor of extracellular signals and transduces them within cells to regulate tissue maintenance, polarity or proliferation [6]. Mutations in at least 27 genes have been shown to cause JS, including: ARL13B, NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, CC2D2A, INPP5E, OFD1, TMEM216, TCTN1, TCTN2, KIF7, TMEM237, CEP41, TMEM138, TMEM231, C5ORF42, TCTN3, IFT172, PDE6D, MKS1, CSPP1, B9D1, B9D2, C2CD3, and CEP120. [3]
Differential Diagnosis List
Joubert syndrome
Dandy-Walker continuum
Mega cisterna magna
Final Diagnosis
Joubert syndrome
Case information
DOI: 10.1594/EURORAD/CASE.15048
ISSN: 1563-4086