The Internet Journal of Radiology ISPUB.COM Volume 7 Number 1

Joubert Syndrome Gyanchand, V Chowdhury, R Dixit, S Singh

Citation Gyanchand, V Chowdhury, R Dixit, S Singh. . The Internet Journal of Radiology. 2006 Volume 7 Number 1.

Abstract Joubert syndrome is a rare autosomal recessive congenital disorder having characteristic clinical features and imaging findings on Magnetic Resonance Imaging (MRI). The 'Molar Tooth' sign is uniformly seen in almost all cases, characterized by an abnormally deep interpeduncular fossa; elongated, thick, and mal-oriented superior cerebellar peduncles; and absent or hypoplastic on axial brain MRI through the junction of the midbrain and hindbrain (isthmus region). Supratentorial structures are unaffected, however corpus callosal agenesis and ventricular dilatation may be found in some cases. Two types of Joubert syndrome has been described on the basis o presence or absence of retinal involvement. The importance of recognizing Joubert syndrome is related to the outcome, its autosomal recessive trait, and the potential complications that may develop. Prenatal diagnosis by ultarsonography and antenatal MRI is also possible.

INTRODUCTION & T2 weighted images showed dysplasia of both superior Joubert syndrome was first described by French neurologist cerebellar peduncles and thinning of the isthmic portion the Marie Joubert. Joubert syndrome is a rare disorder brainstem at pontomesencephalic junction with deep characterized by episodic hypernea, apnea, developmental inerpeduncular fossa resulting in typical ‘ Molar tooth' delay, nystagmus, ataxia and hypotonia. This syndrome is a configuration. The sagittal T1 weighted images showed abnormal horizontally oriented and thickened superior rare disorder inherited as an autosomal recessive trait.(1,2,3). Molar tooth sign, which was first described in Joubert cerebellar peduncles. The more inferior axial images reveal syndrome, can be present in other syndromes recently ‘batwing' configuration of the fourth ventricle. In addition referred to as cerebello-oculo- renal syndromes. the cerebellar vermis was absent with apposition of the cerebellar hemisphere in the midline. Supratentorial CASE REPORT structures appear normal. The corpus callosum was normally HISTORY developed. A 10 month old female patient was referred to our pediatric outpatient department with complaints of psychomotor delay, abnormal eye movement and episodes of hyperpnoea . Patient has undergone surgery for polydactyly in both the hands.

EXAMINATION On physical examination developmental delay, hypotonia, prominent forehead, protruded tongue and hyperpnea was seen. The patient's sibling was diagnosed as having Joubert's syndrome 4 years before. A clinical diagnosis of Joubert's syndrome was made and patient was referred for MRI examination.

IMAGING FINDINGS Multiplanar MR imaging of brain was performed on 1.5T magnet using dedicated circularly phased array head coil. T1

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Figure 1 Figure 3 Figure 1 : T2 weighted axial image at the level of superior Figure 3: T1 weighted sagittal image: isthmus cerebellar peduncle shows deep interpeduncuar fossa and (pontomesencephalic junction) appear thinned . Corpus abnormally oriented superior cerebellar peduncles resulting callosum shows normal morphology and signal pattern. in typical molar tooth appearance.

Figure 4 Figure 4: Sagittal T1 weighted image shows thickened superior cerebellar peduncle. Figure 2 Figure 2: T2 weighted axial image at the level of middle cerebellar peduncles show absence of cerebellar vermis resulting in a midline cleft between the two cerebellar hemispheres. ‘Batwing' configuration of the fourth ventricle is also noted.

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Figure 5 hyperpnea; anomalies of the gracile nuclei and solitary tract Figure 5: True inversion recovery axial image at the level of are thought to contribute to the abnormal respiratory pattern superior cerebellar peduncles also show the molar tootht [9]. sign, vermian hypoplasia and batwing configuration of fourth ventricle The eye abnormalities observed in this disease include complete oculomotor apraxia in horizontal and vertical

directions and ocular coloboma [10]. Inheritance of this disease is said to be autosomal recessive. Recent studies have shown that it is a genetically heterogenous disorder

with one locus pointing to chromosome 9q [11,12]. Based on the presence or absence of retinal dystrophy, 2 types are described. Hypoplasia of the cerebellar vermis with clinical neonatal breathing abnormalities, oculomotor disorders, and hypotonia are present in type I. In addition to these, retinal and renal dysplastic changes are seen in type II, which has a

worse prognosis [13,14]. The clinical history of delayed development, eye movement disorder with failure to develop vision, and abnormal breathing episodes, together with the imaging findings, is classic for Joubert syndrome.

The main imaging findings seen are partial or complete absence of vermis, thickened and abnormal orientation of the superior cerebellar peduncles, thinning of the isthmic portion DISCUSSION of the brainstem with deep interpeduncular cistern producing the classical molar tooth sign. This sign has been reported in Joubert syndrome is a rare that primarily 85% patients of Joubert syndrome. This sign is caused by affects the balance and coordination center of the brain. It is lack of normal decussation of the superior cerebellar characterized by partial or complete absence of the peduncular fibres leading to enlargement of peduncles which cerebellar vermis and dysplastic development of the follow a more horizontal course extending perpendicular to midbrain (4,5,6). This syndrome was first described by Marie the brainstem between the midbrain and cerebellum (15). The Joubert and associates in 1969 in four siblings and one absence of crossing fibres is also responsible for decreased sporadic case that exhibited episodic hyperpnea, abnormal anteroposterior diameter of the brainstem and deep eye movements, ataxia and mental retardation with agenesis interpeduncular cistern (16).The combination of these of cerebellar vermis( ) . 7 findings results in the classical molar tooth configuration on Maria et al. described other abnormalities in Joubert axial MR images of the midbrain. The absence of normal syndrome, such as ocular and oculomotor signs (n = 58, vermis creates a midline cleft between two normal appearing 95%), tongue protrusion (n = 26, 45%), polydactyly (n = 13, cerebellar hemispheres resulting in a characteristic ‘ batwing' 23%), renal abnormalities (n = 9, 16%), megalocephalus (n appearance of the fourth ventricle on axial MR images (17). = 7, 12%), microcephaly (n = 5, 9%), hepatic abnormalities The cerebrum is not affected, although moderate lateral (n = 2, 4%), bradycardia (n = 1, 2%), cardiac murmur (n = 1, ventricular enlargement due to atrophy has been was 2%), cerebral palsy (n = 1, 2%), hypothalamic abnormalities described in 6%–20% of cases, with corpus callosum (n = 1, 2%), and cleft lip (n = 1, 2%) [8]. dysgenesis present in 6%–10% (15,18). In the syndrome, midline structures of the brain-stem have DIFFERENTIAL DIAGNOSIS both anatomic and functional defects. Neuropathological studies reveal agenesis of cerebellar vermis, malformations Molar tooth sign is also seen in Varadi- Papp (oro-facial- of several brainstem nuclei and dysplasia of structures at the digital type IV), COACH, Dekaban-Arima, and Senior- ponto-mesencephalic junction. Extensive brainstem Löken syndromes. A Y-shaped metacarpus, cleft lip, cleft malformation could explain the oculomotor apraxia and palate, and lingual nodule are also seen in Varadi-Papp

3 of 5 Joubert Syndrome syndrome. A Y-shaped metacarpus is characteristic of this Neurol 2004; 11:505-510. 6. Quisling RG, Barkovich AJ, Maria BL. Magnetic syndrome. Oligophrenia, ataxia, coloboma, and hepatic resonance imaging features and classification of central fibrosis are seen in addition to cerebellar vermian hypoplasia nervous system malformations in Joubert syndrome. J Child in COACH syndrome. Renal and retinal pathologies are also Neurol 1999; 14:628-635. 7. Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial seen in Dekaban-Arima and Senior-Löken syndromes, in agenesis of the cerebellar vermis. A syndrome of episodic addition to molar tooth sign, and distinguish them from type hyperpnea, abnormal eye movements, ataxia and retardation. Neurology. 1969 (19) 813-825. II Joubert syndrome, which has a poor prognosis [14]. 8. Maria BL, Quisling RG, Rosainz LC et al. Molar tooth sign in Joubert syndrome: clinical, radiologic and pathologic The diagnosis is important for future procedures that require significance. J Child Neurol 1999; 14:368-376. anesthesia ( ). Patients with Joubert syndrome are extremely 9. Yachnis AT, Rorke LB. Neuropathology of Joubert 19 syndrome. J. sensitive to the respiratory depressant effects of anesthetic Child Neurol. 1999 (14) 655-659. agents, such as opioids, and nitrous oxide. Therefore, these 10. Tusa RJ, Hove MT. Ocular and oculomotor signs in Joubert agents should be avoided, and close perioperative respiratory syndrome. J. Child Neurol. 1999 (14) 621-627. monitoring is essential. 11. Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, CONCLUSION Dobyns WB. Clinical nosologic and genetic aspects of Joubert Joubert syndrome is a rare congenital neurological disorder and related syndromes. J. Child Neurol. 1999 (14) 660-666. with autosomic recessive inheritance. The MRI findings in 12. Saar K, Al-Gazali L, Sztriha L, Rueschendorf F, Nur-E- Kamal this disorder are characteristic with a very limited M, Reis A, Bayoumi R. Homozygosity mapping in families differential diagnosis. With typical clinical and imaging with Joubert syndrome identifies a locus on chromosome 9q34.3 findings the diagnosis is easily made. and evidence for genetic heterogeneity. Am. J. Hum. Genet. CORRESPONDENCE TO 1999,(65) 1666-1671. Dr Gyanchand Deptt. of Radiodiagnosis Lok Nayak Hospital 13. Van Beek EJ, Majoie CB. Case 25: Joubert syndrome. & Maulana Azad Medical College New Delhi, India E mail: Radiology 2000; 216:379-382 [email protected] 14. Gleeson JG, Keler LC, Parisi MA et al. Molar tooth sign of the midbrain-hindbrain junction: occurence in multiple distinct syndromes. Am J Med Genet 2004; 125:125-134. References 15. Kendall B, Kingsley D, Lambert SR, Taylor D, Finn P. 1. Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial Joubert syndrome: a clinico-radiological study. agenesis of the vermis: a syndrome of episodic hyperpnea, Neuroradiology 1990; 31:502-506.[Medline] abnormal eye movements, ataxia, and retardation. Neurology 16. Maria BL, Hoang KB, Tusa RJ, et al. "Joubert 1969; 19:813-825. syndrome" revisited: key ocular motor signs with magnetic 2. Boltshauser E, Isler W. Joubert syndrome: episodic resonance imaging correlation. J Child Neurol hyperpnea, abnormal eye movements, retardation and ataxia, 1997;12:423-430. associated with dysplasia of the cerebellar vermis. 17. Szritha L, Al- Gazali LI,Aithala GR,et al.Joubert's Neuropaediatrie 1977; 8:57-66. syndrome: new cases and review of clinicopathologic 3. Saraiva JM, Baraitser M. Joubert syndrome: a review. Am correlation. Pediatr Neurl 1999;20:274-281 J Med Genet 1992; 43:726-731. 18. Adamsbaum C, Moreau V, Bulteau C, Burstyn J, Lair 4. Zamponi N, Rossi B, Messori A, Polonara G, Regnicolo Milan F, Kalifa G. Vermian agenesis without posterior fossa L, Cardinalli C. Joubert syndrome with associated corpus cyst. Pediatr Radiol 1994; 24:543-546.[Medline] callosum agenesis. Eur J Paediatr Neurol 2002; 6:63-66 19. Habre W, Sims C, D'Souze M. Anaesthetic management 5. Kumandas S, Akcakus M, Coskun A, Gumus H. Joubert of children with Joubert syndrome. Paediatric Anaesth 1997; syndrome: review and report of seven new cases. Eur J 7:251-253.

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Author Information Gyanchand, MD Deptt. of Radiodiagnosis, Lok Nayak hospital & Maulana Azad Medical College

Veena Chowdhury, MD Deptt. of Radiodiagnosis, Lok Nayak hospital & Maulana Azad Medical College

Rashmi Dixit, MD Deptt. of Radiodiagnosis, Lok Nayak hospital & Maulana Azad Medical College

Sapna Singh, MD Deptt. of Radiodiagnosis, Lok Nayak hospital & Maulana Azad Medical College

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