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BMJ Case Rep. 2010; 2010: bcr10.2009.2331.
Published online 2010 April 29. doi:  10.1136/bcr.10.2009.2331
PMCID: PMC3047379
Copyright 2010 BMJ Publishing Group Ltd
Rare disease
Ataxia, hyperpnoea and mental retardation: was it the molar tooth?
Osama S M Amin and Sa’ad Seud Shwani
Department of Neurology, Sulaimaniya General Teaching Hospital, Sulaimaniya City, Iraq
Correspondence to Osama S M Amin, dr.osama.amin/at/gmail.com
Abstract
Joubert’s syndrome is a rare autosomal recessive disease, which is under-diagnosed, associated with other brain and body malformations, and carries a poor prognosis. We describe a 6-year-old boy who presented with non-progressive instability of stance and gait, mental retardation and a new onset of generalised seizures with the typical brain imaging findings of Joubert’s syndrome. We believe this is the first diagnosed case of Joubert’s syndrome in Iraq.
Background
Most cases of Joubert’s syndrome are usually under-diagnosed, associated with many brain and other body malformations, and carry a poor outcome. Approximately, 200 cases only are found all over the world.
A paediatrician referred a 6-year-old boy to our neurology outpatient clinic. The referral letter stated that the patient had ataxic cerebral palsy and had recently developed generalised tonic-clonic seizures, which are poorly responsive to phenytoin 200 mg per day. The paediatrician requested control of these seizures. The child’s mother said that her son developed episodes of rapid breathing during his neonatal period, which improved spontaneously after few minutes, and that his chest plain films were normal during these attacks. Careful history taking did not uncover any perinatal insult and the child’s family history was unremarkable. Reviewing the patient’s past notes showed normal brain CT scan findings (at the ages of 1, 2 and 5.5 y). General medical examination was unremarkable and examination of the nervous system revealed mental subnormality, grossly unstable stance and gait, and nystagmus; no pyramidal signs were obtained and there were no gross involuntary movements. The child’s speech was slow, jerky and explosive. His blood workup was normal. We re-examined the patient’s brain CT scan, which was done 6 months ago. Rapid skimming of this film failed to pick up any abnormal findings; however, careful examination showed that the 4th ventricle is larger than expected and the brainstem is somewhat deformed.
Investigations
Brain MRI was ordered the next day and the typical ‘molar-tooth’ sign of Joubert’s syndrome was detected.
Outcome and follow-up
The patient’s paediatrician was contacted about the true diagnosis and the child’s generalised seizures were controlled with the addition of escalating doses of lamotrigine.
Marie Joubert, who was a French neurologist, reported five cases of children with ataxia, mental retardation, episodic hyperpnoea and eye movement abnormalities; all of those children had hypoplasia of the cerebellar vermis. Four out of those five cases were siblings and one was sporadic. This was in the year 1969.1 Several years later, the constellation of the above clinical features were named Joubert’s syndrome. Joubert’s syndrome is a rare autosomal recessive disorder2 and many culprit genes have been identified: AHI1, CEP290, MKS3, NPHP1 and the recently discovered RPGRIP1L.3,4 Most cases are sporadic; however, less than 40% of familial cases display a mutation in one of these five genes. Joubert’s syndrome is characterised by developmental anomalies of the midline cerebellar vermis and the brainstem. The precise cause of these anomalies is unknown, but they might result from inability of the posterior fossa neuronal structures to cross the midline. There is near total absence of the pyramidal decussation in the lower brainstem. The superior cerebellar peduncles do not cross the midline. The deep dentate nuclei are distorted and there are prominent dysplastic changes in the inferior olivary nuclear complex and its adjacent nuclei.5 However, grossly, the cerebellar hemispheres are usually normal looking.
Patients have a variable combination of ataxia, mental subnormality, delayed language development, hypotonia, episodic hyperpnoea, eye movement abnormalities (usually in the form of ocular apraxia; severe loss of vision and pendular nystagmus are uncommon and are seen in a subgroup of patients only), autistic behaviour, microcephaly, eye coloboma (4%) and retinal dystrophy (50%), meningoencephaloceles, agenesis of the corpus callosum (6–10%), low-set ears, facial dysmorphism, polydactyly (8%), renal cysts, congenital heart anomalies, haemartomas and protrusion of the tongue (2%), and duodenal atresia.6–11 Patients with retinal dystrophy are more likely to display renal cysts and their survival figure is lower than those who have no retinal dystrophic changes.2
The diagnosis of Joubert’s syndrome is a matter of controversy, as there is no consensus about the clear-cut definition of the syndrome. For example, some authors require the presence of episodic hyperpnoea (with other clinical features) plus the absence of cerebellar vermis; others, primarily rely on imaging findings only, while some authors demand the presence of abnormalities in ocular movements to create the fully fledged Joubert’s syndrome.5,12–14 In order to avoid overlap with other similar syndromes, Barreirinho suggested that the following should be considered as major diagnostic criteria for Joubert’s syndrome: hypotonia, ataxia, mental retardation, oculomotor apraxia and the molar tooth sign. Supporting clinical features are abnormal respiratory pattern, retinal pigmentation, renal abnormalities and facial dysmorphism.15
The importance of knowing Joubert’s syndrome lies in its prognosis; the outlook is poor in the majority. A follow-up study in 19 Joubert’s children showed that 3 patients died before the age of 3 y and those who survived beyond this age were left with severe psychomotor retardation.14 However, Pascual-Castroviejo described two siblings with Joubert’s syndrome who have a relatively normal evolution.16
After carefully reviewing the patient’s brain CT scan (figures 1 and ​and2),2), we found the molar tooth sign, which was more obvious on the subsequent brain MRI film (figures 3 and ​and4).4). In a classical patient, the cerebellar vermis appears partially or entirely absent, the cerebellar peduncles are hypoplastic (and thickened), the ponto-mesencephalic junction is elongated with a deep interpeduncular fossa and the 4th ventricle appears deformed. The combination of these changes results in the so-called molar tooth sign.17–19 It should be noted that the absence of cerebellar vermis per se does not correspond to Joubert’s syndrome; it is also absent in Dandy-Walker syndrome and Down syndrome.20 On the other hand, the molar tooth sign can be found in 85% of Joubert’s cases; about 13% of those patients show additional brain malformations.17
Figure 1
Figure 1
Non-contrast brain CT scan of our patient at the level of the midbrain, which was done several months before the brain MRI. The molar tooth sign can easily escape detection. Note that the cerebellar hemispheres meet in the midline with a bat-wing configuration. (more ...)
Figure 2
Figure 2
The patient’s brain CT scan at the level of the mid-pons. Note the absence of the midline cerebellar vermis and, because of this, the cerebellar hemispheres meet in the midline with a bat-wing configuration.
Figure 3
Figure 3
An axial T2-weighted brain MRI image of the patient at the level of the midbrain displaying the molar tooth sign, which is created by the combination of deep inter-peduncular fossa, slender superior cerebellar peduncles and enlarged 4th ventricle. The (more ...)
Figure 4
Figure 4
Axial T2-weighted brain MRI image of the patient at the level of the midbrain showing the constituents of the molar tooth.
We think that the radiologist and the paediatrician missed the molar tooth sign (which was somewhat subtle) on the brain CT scans and the diagnosis of ataxic cerebral palsy was given accordingly. The child’s neonatal hyperventilation episodes most likely represent the syndrome’s hyperpnoea. His newest feature was the generalised seizures, which are actually uncommon in Joubert’s syndrome.15 The child would have also benefited from cognitive therapy.21
We have reviewed the Baghdad teaching hospital patients’ registry (including its neurology outpatient department’s records) and have contacted neurologists in other hospitals looking for similar cases. We believe this is the first diagnosed case of Joubert’s syndrome in Iraq. Cases of Joubert’s syndrome are under-diagnosed worldwide and Iraq is no exception.
Learning points
  • Joubert’s syndrome is under-diagnosed and should always be considered in children with non-progressive ataxia, mental retardation and neonatal hyperpnea.
  • The presence of molar tooth sign is not pathognomonic for Joubert’s syndrome and its absence does not refute the diagnosis of Joubert’s syndrome.
  • The importance of knowing this syndrome lies in its poor outlook; other brain and body malformations/defects should always be searched for.
Footnotes
Competing interests: Dr Osama SM Amin owns www.Neurology4MRCP.com. This website is free in providing teaching materials for the MRCP examinations. From July 2009 most of the publications will no longer be free. Dr Osama SM Amin receives royalties for the books Mock Papers for MRCPI part I, Self-assessment for MRCP (UK) part 1 and Self-Assessment for MRCP part II.
Patient consent: Patient/guardian consent was obtained for publication.
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