Alternative titles; symbols
SNOMEDCT: 253175003, 716997004; ORPHA: 475; DO: 0110980;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9q34.3 | Joubert syndrome 1 | 213300 | Autosomal recessive | 3 | INPP5E | 613037 |
A number sign (#) is used with this entry because of evidence that Joubert syndrome-1 (JBTS1) is caused by homozygous mutation in the INPP5E gene (613037) on chromosome 9q34.
Joubert syndrome is a clinically and genetically heterogeneous group of disorders characterized by hypoplasia of the cerebellar vermis with the characteristic neuroradiologic 'molar tooth sign,' and accompanying neurologic symptoms, including dysregulation of breathing pattern and developmental delay. Other variable features include retinal dystrophy and renal anomalies (Saraiva and Baraitser, 1992; Valente et al., 2005).
Genetic Heterogeneity of Joubert Syndrome
See also JBTS2 (608091), caused by mutation in the TMEM216 gene (613277) on chromosome 11q13; JBTS3 (608629), caused by mutation in the AHI1 gene (608894) on chromosome 6q23; JBTS4 (609583), caused by mutation in the NPHP1 gene (607100) on chromosome 2q13; JBTS5 (610188), caused by mutation in the CEP290 gene, also called NPHP6 (610142), on chromosome 12q21; JBTS6 (610688), caused by mutation in the TMEM67 gene (609884) on chromosome 8q21; JBTS7 (611560), caused by mutation in the RPGRIP1L gene (610937) on chromosome 16q12; JBTS8 (612291), caused by mutation in the ARL13B (608922) on chromosome 3q11; JBTS9 (612285), caused by mutation in the CC2D2A gene (612013) on chromosome 4p15; JBTS10 (300804), caused by mutation in the CXORF5 gene (300170) on chromosome Xp22; JBTS11 (see 613820), caused by mutation in the TTC21B gene (612014) on chromosome 2q24; JBTS12 (see 200990), caused by mutation in the KIF7 gene (611254) on chromosome 15q26; JBTS13 (614173), caused by mutation in the TCTN1 gene (609863) on chromosome 12q24; JBTS14 (614424), caused by mutation in the TMEM237 gene (614423) on chromosome 2q33; JBTS15 (614464), caused by mutation in the CEP41 gene (610523) on chromosome 7q32; JBTS16 (614465), caused by mutation in the TMEM138 gene (614459) on chromosome 11q; JBTS17 (614615), caused by mutation in the CPLANE1 gene (614571) on chromosome 5p13; JBTS18 (614815), caused by mutation in the TCTN3 gene (613847) on chromosome 10q24; JBTS19 (see 614844), caused by mutation in the ZNF423 gene (604577) on chromosome 16q12; JBTS20 (614970), caused by mutation in the TMEM231 gene (614949) on chromosome 16q23; JBTS21 (615636), caused by mutation in the CSPP1 gene (611654) on chromosome 8q13; JBTS22 (615665), caused by mutation in the PDE6D gene (602676) on chromosome 2q37; JBTS23 (616490), caused by mutation in the KIAA0586 gene (610178) on chromosome 14q23; JBTS24 (616654), caused by mutation in the TCTN2 gene (613846) on chromosome 12q24; JBTS25 (616781), caused by mutation in the CEP104 gene (616690) on chromosome 1p36; JBTS26 (616784), caused by mutation in the KATNIP gene (616650) on chromosome 16p12; JBTS27 (617120), caused by mutation in the B9D1 gene (614144) on chromosome 17p11; JBTS28 (617121), caused by mutation in the MKS1 gene (609883) on chromosome 17q23; JBTS29 (see 617562), caused by mutation in the TMEM107 gene (616183) on chromosome 17p13; JBTS30 (617622), caused by mutation in the ARMC9 gene (617612) on chromosome 2q37; JBTS31 (617761), caused by mutation in the CEP120 gene (613446) on chromosome 5q23; JBTS32 (617757), caused by mutation in the SUFU gene (607035) on chromosome 10q24; JBTS33 (617767), caused by mutation in the PIBF1 gene (607532) on chromosome 13q21; JBTS34 (see 614175), caused by mutation in the B9D2 gene (611951) on chromosome 19q13; JBTS35 (618161), caused by mutation in the ARL3 gene (604695) on chromosome 10q24; JBTS36 (618763), caused by mutation in the FAM149B1 gene (618413) on chromosome 10q22; JBTS37 (619185), caused by mutation in the TOGARAM1 gene (617618) on chromosome 14q21; JBTS38 (619476), caused by mutation in the KIAA0753 gene (617112) on chromosome 17p13; JBTS39 (619562), caused by mutation in the TMEM218 gene (619285) on chromosome 11q24; and JBTS40 (619582), caused by mutation in the IFT74 gene (608040) on chromosome 9p21.
De Haene (1955) collected from the literature 4 cases of total and 7 cases of partial agenesis of the vermis of the cerebellum, and added the only familial example: 3 brothers (1 autopsy) died at ages 4 to 8 years, the illness being characterized by tremor and hypotonia.
Boltshauser and Isler (1977), who suggested the designation Joubert syndrome based on the article by Joubert et al. (1969) (see JBTS17, 614615), described 3 cases, 2 of them sibs. Detailed neuropathologic findings on 1 of these patients were reported by Friede and Boltshauser (1978). Boltshauser et al. (1981) reported 2 affected sisters whose parents were consanguineous.
Egger and Baraitser (1984) suggested that the sibs reported by Gustavson et al. (1971) and by Haumont and Pelc (1983) had the Joubert syndrome, not the Mohr syndrome (252100).
Kendall et al. (1990) reviewed the radiologic findings in 16 consecutive cases. Cantani et al. (1990) reviewed 53 published cases. In the children of healthy, consanguineous Turkish parents, van Dorp et al. (1991) observed a severely retarded male child with neurologic anomalies including Dandy-Walker malformation, hypoplasia of the corpus callosum, occipital meningoencephalocele, and bilateral coloboma of the optic nerve with retrobulbar cystic mass. The detailed findings at autopsy in an affected female fetus from the mother's second pregnancy were presented. The fetus showed hypognathia, occipital meningoencephalocele, and empty posterior fossa.
Squires et al. (1991) described an affected infant, born to nonconsanguineous parents, who had episodic tachypnea, agenesis of the cerebellar vermis, a complex cardiac malformation, cutaneous dimples over the wrists and elbows, telecanthus, and micrognathia.
Lindhout et al. (1980) and Laverda et al. (1984) described associated chorioretinal coloboma (see 243910). Saraiva and Baraitser (1992) reviewed 72 previously reported patients and 29 new patients with the possible diagnosis of Joubert syndrome. They presented data on 94 patients that fulfilled their criteria and proposed a classification into 2 groups: those with retinal dystrophy and those without. Retinal dystrophy ran true in families and was never absent when renal cysts were reported.
Maria et al. (1999) reviewed the clinical features of Joubert syndrome and provided revised diagnostic criteria. They pointed out that careful examination of the face shows a characteristic appearance: large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis (occasionally), upturned nose with evident nostrils, open mouth (the mouth tends to have an oval shape early on, a 'rhomboid' appearance later, and finally can appear triangular with downturned mouth angles), tongue protrusion and rhythmic tongue motions, and occasionally low-set and tilted ears. Neuroophthalmologic examination shows oculomotor apraxia. Most children with this disorder have hyperpnea intermixed with central apnea in the neonatal period. Neuroimaging of the head in the axial plane demonstrates the 'molar tooth sign,' that is, deep posterior interpeduncular fossa, thick and elongated superior cerebellar peduncles, and hypoplastic or aplastic superior cerebellar vermis. See their Table 1 for the proposed revised diagnostic criteria.
Fennell et al. (1999) reported on cognitive, behavioral, and developmental findings of follow-up studies of Joubert syndrome. The parents' reports of behaviors showed problems with temperament, hyperactivity, aggressiveness, and dependency, as well as problems in physical development and care that were thought to be related to the neurologic handicaps. Parents' reports of developmental attainments revealed that only 3 of 40 children were functioning in the borderline range, with the rest scoring in the severely impaired range.
The studies reported by Yachnis and Rorke (1999) suggested that, in addition to vermal agenesis, Joubert syndrome is characterized by malformation of multiple brainstem structures. The latter could explain certain clinical features of the syndrome, including episodic hyperpnea and oculomotor apraxia. Brainstem malformation is represented by the 'molar tooth sign' on magnetic resonance imaging (Maria et al., 1999).
Raynes et al. (1999) described 3 sisters with Joubert syndrome, 2 of whom were monozygotic twins with highly discordant phenotypes. The twins were born at 34 weeks' gestation with discordant birth weights. Their anatomic, neurologic, and developmental status also differed greatly: twin B was able to walk and run, and was verbal, unlike twin A who was wheelchair-bound, severely retarded, nonverbal, and autistic. Abnormal eye movements and retinal dysplasia were features in all 3 girls, but none had renal cysts demonstrable by ultrasonography. Magnetic resonance images showed the 'molar tooth sign,' the radiologic hallmark of Joubert syndrome, although only 1 twin, the more severely handicapped, had severe hypoplasia of the cerebellar hemispheres. Raynes et al. (1999) discussed the basis for the phenotypic discordance in the twins.
Valente et al. (2005) reported 2 families with Joubert syndrome linked to chromosome 9q (JBTS1). In a family of Italian origin, 2 sibs had hypotonia that evolved into ataxia, marked oculomotor apraxia, and moderate visual reduction with mild pigmentary changes. Intelligence and kidney function were normal in both patients. In the second family, originating from Oman, an affected child had a typical neurologic phenotype with mental retardation, but no breathing dysregulation. Fundus exam and kidney function were normal. All of these patients had the molar tooth sign on MRI.
In a retrospective review of midsagittal T1-weighted brain MRI studies of 20 patients with Joubert syndrome ranging in age from 18 days to 23 years, Spampinato et al. (2008) found absence of decussation of the superior cerebellar peduncles in all 6 patients over 30 months of age. Decussation was well seen on brain scans of 16 healthy controls over 30 months of age, but could not be visualized in any individuals, healthy or patients, under 30 months of age. Spampinato et al. (2008) concluded that the lack of superior cerebellar commissural fibers in Joubert syndrome accounted in part for the classic molar tooth sign observed in patients with the disorder.
Braddock et al. (2007) analyzed the dysmorphic facial features of 34 children and young adults with Joubert syndrome who were not classified by molecular analysis. Findings included long face, frontal prominence, bitemporal narrowing, ptosis, prominent nasal bridge and tip, prognathism, eyebrow abnormalities, trapezoid-shaped mouth, lower lip eversion, and thick ear lobes. Anthropometric analysis showed several significant differences in measurements including bizygomatic, frontal, nasal, and mandibular dimensions. Facial characteristics appeared to become more distinct with age. Despite these findings, Braddock et al. (2007) noted that there was extreme variability likely resulting from genetic heterogeneity.
To localize the region responsible for Joubert syndrome, Saar et al. (1999) performed a whole-genome scan in 2 consanguineous families of Arabian-Iranian origins with multiple affected members. In 1 family of Omani origin (Sztriha et al., 1999), Saar et al. (1999) detected linkage to the telomeric region of 9q, close to marker D9S158, with a multipoint lod score of Z = 3.7. The second family did not show linkage to this region, giving the first indication of genetic heterogeneity underlying Joubert syndrome. These findings were supported by subsequent analysis of 2 smaller families, one compatible with linkage to 9q34.3 and the other unlinked. The locus on 9q34.3 is referred to as JBTS1. Valente et al. (2005) reported 2 additional affected female twins from 1 of the families reported by Saar et al. (1999).
Heterogeneity
Blair et al. (2002) investigated a cohort of apparently unrelated North American Joubert syndrome pedigrees for association with the 9q34 and 17p11.2 loci that had previously been implicated and excluded these 2 loci in all cases where data were informative. Analysis of an additional 21 unrelated JBTS patients showed no evidence of homozygosity at the 9q34 and 17p11.2 loci that would suggest inheritance of founder JBTS mutations or unreported consanguinity. Together, these data suggested that one or more major loci for JBTS remained to be identified.
Natacci et al. (2000) reported a 22-year-old woman with a deletion in the short arm of chromosome 17 who presented with the clinical manifestations of both Smith-Magenis syndrome (SMS; 182290) and Joubert syndrome. Facial anomalies, brachydactyly, severe mental retardation, and self-injuring behavior were attributed to SMS, whereas the cerebellar vermis hypoplasia, hypotonia, ataxic gait, developmental delay, and abnormal respiratory pattern suggested Joubert syndrome. By fluorescence in situ hybridization analyses with YAC mapping to the 17p11.2 region, as well as locus-specific probes generated through a novel procedure, they established that the deletion encompasses a 4-Mb interval. The deletion differed from that commonly found in SMS in its telomeric boundary, and was more distal than usually observed. The presence of the Joubert syndrome phenotype in this patient and the detection of an unusual SMS deletion suggested the presence of a Joubert syndrome gene in close proximity to the SMS locus. Although Joubert syndrome has been linked to 9q34.3 in some families, no linkage to this area has been demonstrated in other families.
The transmission pattern of Joubert syndrome-1 in the families reported by Bielas et al. (2009) was consistent with autosomal recessive inheritance.
In affected members of 7 families with Joubert syndrome, Bielas et al. (2009) identified 5 different homozygous mutations in the INPP5E gene (see, e.g., 613037.0002-613037.0005). Three families were from the United Arab Emirates, 1 from Turkey, 1 from Egypt, and 2 from Italy. All of the mutations were in the catalytic domain of the protein, and all mutant proteins showed decreased phosphatase activity. The findings implied a link between PtdIns signaling and ciliopathies.
Associations Pending Confirmation
For discussion of a possible association between Joubert syndrome and mutation in the PDPR gene, see 617835.0001.
Exclusion Studies
Because of its expression in the developing cerebellum and because of an associated mutation of Wnt1 in the 'swaying' mouse, Pellegrino et al. (1997) evaluated the WNT1 gene (164820) as a candidate gene for Joubert syndrome. The investigators ascertained a cohort of 50 patients with Joubert syndrome to evaluate the presence of associated malformations and to initiate studies leading to the identification of the responsible gene. Only 8% of patients had polydactyly, 4% had colobomas, 2% had renal cysts, and 2% had soft tissue tumors of the tongue. No mutations of the WNT1 gene were found in the patients of the cohort.
Blair et al. (2002) undertook mutation analysis of several functional candidate genes in a total of 26 unrelated JBTS patients and excluded EN1 (131290), EN2 (131310), and FGF8 (600483) from a direct pathogenic role in JBTS. The BARHL1 gene (605211), which localizes to 9q34 and had previously been proposed as a strong positional candidate gene for JBTS, was also investigated and excluded from involvement in JBTS that is linked to 9q34.
In 2 sibs and 1 unrelated patient with Joubert syndrome, Gould and Walter (2004) demonstrated no abnormality of the BARHL1 gene or the BARX1 gene (603260) on 9q12.
Modifier Genes
Khanna et al. (2009) presented evidence that a common allele in the RPGRIP1L gene (A229T; 610937.0013) may be a modifier of retinal degeneration in patients with ciliopathies due to other mutations, including JBTS.
Valente et al. (2003) used the designation cerebellooculorenal syndromes (CORSs) for the clinically and genetically heterogeneous autosomal recessive syndromes, including Joubert syndrome, that share a complex neuroradiologic malformation resembling a molar tooth on brain axial images. They described a consanguineous Sicilian family showing linkage of a cerebellooculorenal syndrome (without ocular involvement except nystagmus), showing linkage to the pericentromeric region of chromosome 11. Valente et al. (2003) and Keeler et al. (2003) proposed that the locus be called CORS2 (608091), with CORS1 suggested as an alternative designation for the JBTS1 locus on 9q34.
The classic article by Joubert et al. (1969) was reprinted with a cluster of papers on this disorder.
Bielas, S. L., Silhavy, J. L., Brancati, F., Kisseleva, M. V., Al-Gazali, L., Sztriha, L., Bayoumi, R. A., Zaki, M. S., Abdel-Aleem, A., Rosti, R. O., Kayserili, H., Swistun, D., and 13 others. Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nature Genet. 41: 1032-1036, 2009. [PubMed: 19668216] [Full Text: https://doi.org/10.1038/ng.423]
Blair, I. P., Gibson, R. R., Bennett, C. L., Chance, P. F. Search for genes involved in Joubert syndrome: evidence that one or more major loci are yet to be identified and exclusion of candidate genes EN1, EN2, FGF8, and BARHL1. Am. J. Med. Genet. 107: 190-196, 2002. [PubMed: 11807898]
Boltshauser, E., Herdan, M., Dumermuth, G., Isler, W. Joubert syndrome: clinical and polygraphic observations in a further case. Neuropediatrics 12: 181-191, 1981. [PubMed: 7266779] [Full Text: https://doi.org/10.1055/s-2008-1059650]
Boltshauser, E., Isler, W. Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis. Neuropadiatrie 8: 57-66, 1977. [PubMed: 576733] [Full Text: https://doi.org/10.1055/s-0028-1091505]
Braddock, S. R., Henley, K. M., Maria, B. L. The face of Joubert syndrome: a study of dysmorphology and anthropometry. Am. J. Med. Genet. 143A: 3235-3242, 2007. [PubMed: 18000967] [Full Text: https://doi.org/10.1002/ajmg.a.32099]
Cantani, A., Lucenti, P., Ronzani, G. A., Santoro, C. Joubert syndrome: review of the fifty-three cases so far published. Ann. Genet. 33: 96-98, 1990. [PubMed: 2241092]
De Haene, A. Agenesie partielle du vermis du cervelet a caractere familial. Acta Neurol. Psychiat. Belg. 55: 622-628, 1955. [PubMed: 13275283]
Egger, J., Baraitser, M. Mohr syndrome variant or Joubert-Boltshauser syndrome? (Letter) Clin. Genet. 25: 86-87, 1984. [PubMed: 6705246] [Full Text: https://doi.org/10.1111/j.1399-0004.1984.tb00470.x]
Fennell, E. B., Gitten, J. C., Dede, D. E., Maria, B. L. Cognition, behavior, and development in Joubert syndrome. J. Child Neurol. 14: 592-596, 1999. [PubMed: 10488904] [Full Text: https://doi.org/10.1177/088307389901400907]
Friede, R. L., Boltshauser, E. Uncommon syndromes of cerebellar vermis aplasia. I: Joubert syndrome. Dev. Med. Child Neurol. 20: 758-763, 1978. [PubMed: 729929] [Full Text: https://doi.org/10.1111/j.1469-8749.1978.tb15307.x]
Gould, D. B., Walter, M. A. Mutational analysis of BARHL1 and BARX1 in three new patients with Joubert syndrome. (Letter) Am. J. Med. Genet. 131A: 205-208, 2004. [PubMed: 15487006] [Full Text: https://doi.org/10.1002/ajmg.a.30227]
Gustavson, K. H., Kreuger, A., Petersen, P. O. Syndrome characterized by lingual malformation, polydactyly, tachypnea and mental retardation (Mohr syndrome). Clin. Genet. 2: 261-266, 1971. [PubMed: 5146584] [Full Text: https://doi.org/10.1111/j.1399-0004.1971.tb00287.x]
Haumont, D., Pelc, S. The Mohr syndrome: are there two variants? Clin. Genet. 24: 41-46, 1983. [PubMed: 6352094] [Full Text: https://doi.org/10.1111/j.1399-0004.1983.tb00067.x]
Joubert, M., Eisenring, J. J., Robb, J. P., Andermann, F. Familial agenesis of the cerebellar vermis: a syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology 19: 813-825, 1969. Note: Reprinted in J. Child Neurol. 14: 554-564, 1999. [PubMed: 5816874] [Full Text: https://doi.org/10.1212/wnl.19.9.813]
Keeler, L. C., Marsh, S. E., Leeflang, E. P., Woods, C. G., Sztriha, L., Al-Gazali, L., Gururaj, A., Gleeson, J. G. Linkage analysis in families with Joubert syndrome plus oculo-renal involvement identifies the CORS2 locus on chromosome 11p12-q13.3. Am. J. Hum. Genet. 73: 656-662, 2003. [PubMed: 12917796] [Full Text: https://doi.org/10.1086/378206]
Kendall, B., Kingsley, D., Lambert, S. R., Taylor, D., Finn, P. Joubert syndrome: a clinico-radiological study. Neuroradiology 31: 502-506, 1990. [PubMed: 2352633] [Full Text: https://doi.org/10.1007/BF00340131]
Khanna, H., Davis, E. E., Murga-Zamalloa, C. A., Estrada-Cuzcano, A., Lopez, I., den Hollander, A. I., Zonneveld, M. N., Othman, M. I., Waseem, N., Chakarova, C. F., Maubaret, C., Diaz-Font, A., and 22 others. A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nature Genet. 41: 739-745, 2009. [PubMed: 19430481] [Full Text: https://doi.org/10.1038/ng.366]
Laverda, A. M., Saia, O. S., Drigo, P., Danieli, E., Clementi, M., Tenconi, R. Chorioretinal coloboma and Joubert syndrome: a nonrandom association. J. Pediat. 105: 282-284, 1984. [PubMed: 6747764] [Full Text: https://doi.org/10.1016/s0022-3476(84)80133-x]
Lindhout, D., Barth, P. G., Valk, J., Boen-Tan, T. N. The Joubert syndrome associated with bilateral chorioretinal coloboma. Europ. J. Pediat. 134: 173-176, 1980. [PubMed: 7439204] [Full Text: https://doi.org/10.1007/BF01846041]
Maria, B. L., Boltshauser, E., Palmer, S. C., Tran, T. X. Clinical features and revised diagnostic criteria in Joubert syndrome. J. Child Neurol. 14: 583-591, 1999. [PubMed: 10488903] [Full Text: https://doi.org/10.1177/088307389901400906]
Natacci, F., Corrado, L., Pierri, M., Rossetti, M., Zuccarini, C., Riva, P., Miozzo, M., Larizza, L. Patient with large 17p11.2 deletion presenting with Smith-Magenis syndrome and Joubert syndrome phenotype. Am. J. Med. Genet. 95: 467-472, 2000. [PubMed: 11146468] [Full Text: https://doi.org/10.1002/1096-8628(20001218)95:5<467::aid-ajmg11>3.0.co;2-t]
Pellegrino, J. E., Lensch, M. W., Muenke, M., Chance, P. F. Clinical and molecular analysis in Joubert syndrome. Am. J. Med. Genet. 72: 59-62, 1997. [PubMed: 9295076] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19971003)72:1<59::aid-ajmg12>3.0.co;2-t]
Raynes, H. R., Shanske, A., Goldberg, S., Burde, R., Rapin, I. Joubert syndrome: monozygotic twins with discordant phenotypes. J. Child Neurol. 14: 649-654, 1999. [PubMed: 10511337] [Full Text: https://doi.org/10.1177/088307389901401005]
Saar, K., Al-Gazali, L., Sztriha, L., Rueschendorf, F., Nur-E-Kamal, M., Reis, A., Bayoumi, R. Homozygosity mapping in families with Joubert syndrome identifies a locus on chromosome 9q34.3 and evidence for genetic heterogeneity. Am. J. Hum. Genet. 65: 1666-1671, 1999. [PubMed: 10577920] [Full Text: https://doi.org/10.1086/302655]
Saraiva, J. M., Baraitser, M. Joubert syndrome: a review. Am. J. Med. Genet. 43: 726-731, 1992. [PubMed: 1341417] [Full Text: https://doi.org/10.1002/ajmg.1320430415]
Spampinato, M. V., Kraas, J., Maria, B. L., Walton, Z. J., Rumboldt, Z. Absence of decussation of the superior cerebellar peduncles in patients with Joubert syndrome. Am. J. Med. Genet. 146A: 1389-1394, 2008. [PubMed: 18412277] [Full Text: https://doi.org/10.1002/ajmg.a.32282]
Squires, L. A., Raymond, G., Neumeyer, A. M., Krishnamoorthy, K. S., Buyse, M. L. Dysmorphic features of Joubert syndrome. Dysmorph. Clin. Genet. 5: 72-77, 1991.
Sztriha, L., Al-Gazali, L. I., Aithala, G. R., Nork, M. Joubert's syndrome: new cases and review of clinicopathologic correlation. Pediat. Neurol. 20: 274-281, 1999. [PubMed: 10328276] [Full Text: https://doi.org/10.1016/s0887-8994(98)00154-4]
Valente, E. M., Marsh, S. E., Castori, M., Dixon-Salazar, T., Bertini, E., Al-Gazali, L., Messer, J., Barbot, C., Woods, C. G., Boltshauser, E., Al-Tawari, A. A., Salpietro, C. D., Kayserili, H., Sztriha, L., Gribaa, M., Koenig, M., Dallapiccola, B., Gleeson, J. G. Distinguishing the four genetic causes of Joubert syndrome-related disorders. Ann. Neurol. 57: 513-519, 2005. Note: Erratum: Ann. Neurol. 57: 934 only, 2005. [PubMed: 15786477] [Full Text: https://doi.org/10.1002/ana.20422]
Valente, E. M., Salpietro, D. C., Brancati, F., Bertini, E., Galluccio, T., Tortorella, G., Briuglia, S., Dallapiccola, B. Description, nomenclature, and mapping of a novel cerebello-renal syndrome with the molar tooth malformation. Am. J. Hum. Genet. 73: 663-670, 2003. [PubMed: 12908130] [Full Text: https://doi.org/10.1086/378241]
van Dorp, D. B., Palan, A., Lan Kwee, M., Barth, P. G., van der Harten, J. J. Joubert syndrome: a clinical and pathological description of an affected male and a female fetus from the same sibship. Am. J. Med. Genet. 40: 100-104, 1991. [PubMed: 1887836] [Full Text: https://doi.org/10.1002/ajmg.1320400121]
Yachnis, A. T., Rorke, L. B. Neuropathology of Joubert syndrome. J. Child Neurol. 14: 655-659, 1999. [PubMed: 10511338] [Full Text: https://doi.org/10.1177/088307389901401006]