Joubert syndrome
Joubert syndrome | |
ICD-10 | Q04.3 |
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ICD-9 | 742.2 |
DiseasesDB | 30688 |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]
Synonyms and Keywords: Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; Joubert-Boltshauser syndrome; JBTS1; CPD4; Cerebellooculorenal syndrome 1; CORS1; Joubert syndrome 1
Overview
Joubert syndrome is a rare genetic disorder that affects the areas of the cerebellar vermis and brain stem in the brain that controls balance and coordination. Joubert syndrome follows autosomal recessive pattern of inheritance. In The United States of America in order to categorise a condition as a rare disease it should affect fewer than 200,000 people. Rare diseases also called as orphan diseases. Orphan Drug Act was passed on 1983 by congress for the rare diseases. Today an average of 25-30 million americans have been reported with rare diseases. The number of people with individual rare disease may be less but overall the number of people with rare diseases are large in number.
Historical perspective
- In year 1955, the first reported cases of Joubert syndrome which are partial agenesis of the vermis of the cerebellum was collected by De Haene.[1]
- In year 1969, Joubert syndrome was first discovered in in four siblings by Dr. Marie Joubert et al.[2][3]
- In year 1977, Joubert syndrome name was first suggested by Boltshauser and Isler.
- In year 1978, Friede and Boltshauser are the first to describe neuropathologic findings in one patient with joubert syndrome.[4][5]
- In year 1978, Boltshauser et al are the first first to describe two sisters who are having joubert syndrome whose parents were consanguineous.[6][7]
Classification
- Joubert syndrome may be classified according to gene location of the mutation into many subtypes of these JBTS1 and JBTS2 are the most common and important subtypes:[8][9]
Phenotype | Location of mutation | Gene involved | Inheritance pattern |
---|---|---|---|
JOUBERT SYNDROME 1(JBTS1) | 9q34.3 | INPP5E | Autosomal recessive |
JOUBERT SYNDROME 2(JBTS2) | 11q12.2 | TMEM216 | Autosomal recessive |
Pathophysiology
- It is understood that Joubert syndrome is most commonly caused by mutation in basal body genes in INPP5E and TMEM216 gene on chromosome 9q34 and 11q12.2 respectively.
- Other genes involved in developing of joubert syndrome are as follows:[10][11]
INPP5E (Inositol polyphosphate-5-phosphatase E)
- JBTS1 gene(INPP5E) plays an important role in Inositol polyphosphate-5-phosphatase E pathway on chromosome 9q34.3.[12][13][14]
- Missense mutation in Inositol polyphosphate-5-phosphatase E pathway leads to truncated protein
TMEM216(Transmembrane protein 216)
- JBTS2 gene(TMEM216 ) also plays an important role in Inositol polyphosphate-5-phosphatase on chromosome 11q12.2
- The mechanism by which the mutation leads to truncated protein is unknown
AHI1(Abelson Helper Integration Site 1)
- JBTS3 gene(AHI1) plays an important role in the formation of jouberin on chromosome 6q23.[15][16][17][18]
- Nonsense mutation in the AHI1 leads to truncated protein (Jouberin) and cause the disease[19][20]
NPHP1(Nephrocystin 1)
- JBTS4 gene(NPHP1) on chromosome 2q13 plays an important role in the formation of nephrocystin-1 protein[21][22][23][24]
- Missense mutation in the NPHP1 leads to truncated protein (Nephrocystin-1 protein) and cause the disease[25][26][27]
CEP290(Centrosomal protein 290)
- JBTS5 gene(CEP290) on chromosome12q21.3 plays an important role in the formation of centrosomal protein of 290 kDa protein[28][29]
- Nonsense mutation in the CEP290 leads to truncated protein (Centrosomal protein of 290 kDa protein) and cause the disease
TMEM67(Transmembrane protein 67) / MKS3(Transmembrane protein meckelin)
- JBTS6 gene(TMEM67/MKS3) on chromosome 8q21.1-q22.1 plays an important role in the formation of meckelin protein[30][31]
- Missense, splice mutation leads to truncated protein (meckelin protein) and cause the disease
RPGRIP1L
- JBTS7 gene(RPGRIP1L) on chromosome 16q12.2 plays an important role in the formation of RPGR-interacting protein 1-like protein[32]
- Missense, nonsense, splice mutation leads to truncated protein (RPGR-interacting protein 1-like protein) and cause the disease
ARL13B
- JBTS7 gene(ARL13B) on chromosome 3q11.2 plays an important role in the formation of ADP-Ribosylation factor-like 13B protein
- Missense mutation leads to truncated protein (ADP-Ribosylation factor-like 13B protein) and cause the disease
CC2D2A
- JBTS7 gene(CC2D2A) on chromosome 4p15.3 plays an important role in the formation of coiled-coil and C2 Domains-containing protein 2A protein
- Missense, nonsense, splice, frame shift mutation leads to truncated protein(C2 Domains-containing protein 2A protein) and cause the disease
Causes
Genetic Causes
- Joubert syndrome is caused by mutations in the following genes INPP5E, TMEM216, AHI1, NPHP1, CEP290, RPGRIP1L, ARL13B, and CC2D2A.[33][34]
Epidemiology and Demographics
Incidence
- The incidence of joubert syndrome is approximately 1 per 80,000 individuals to 1 per 100,000 individuals worldwide.[35][36][37]
- Till now only 200 cases of joubert syndrome were published in the literature.
Prevalence
- The prevalence of joubert syndrome is approximately 1 per 100,000 in the United States.[38]
Age
- Joubert syndrome commonly affects newborns in the first 6 months of life.
Risk Factors
- There are no established risk factors for joubert syndrome.
Physical Examination
HEENT
- Facial features: Facial features in patients with joubert syndrome are very prominent and have a significant importance in diagnosis.[39][40][41][42][43][44]
- Broad forehead
- High rounded eyebrows
- Epicanthal folds
- Ptosis
- Widely spaced eyes
- Upturned nose with evident nostrils
- Low-set ears
- Triangular-shaped mouth(Rhomboid appearance)
- Tongue protrusion
- Oculomotor apraxia(OMA): Patients with oculomotor apraxia in joubert syndrome have difficulty in moving the eyes from one side to another side.[48][49][50][51][52][53]
Lungs
Neuromuscular
- Ataxia: Very prominent and most common physical findings in patients with joubert syndrome[59][60][61]
Natural History, Complications, and Prognosis
Natural History
- The symptoms of joubert syndrome usually develop in the first decade of life, and start with symptoms such as episodic apnea, ataxia and intellectual disability.
Complications
Common complications of joubert syndrome include:
- Developmental delay
- Abnormal eye movements
- Hypotonia
- Cystic dysplasia
- Nephronophthisis
Prognosis
- The development or underdevelopment of cerebellar vermis is the main prognostic factor in patients with joubert syndrome.[66][67][68][69]
- Involvement of other organs such as kidney and liver also plays a significant role in prognosis.[70]
Diagnostic Study of Choice
- Magnetic resonance imaging(MRI) is the gold standard test for the diagnosis of joubert syndrome, shows the following features on MRI
- Molar tooth sign: Pathognomonic of joubert syndrome
- Vermian dysgenesis and horizontal superior cerebellar peduncle elongation represents the molar tooth sign
- Molar tooth sign: Pathognomonic of joubert syndrome
Medical therapy
References
- ↑ Stoffels, C.; Babin, E. (1976). "Angiography of incomplete lobulation of the cerebellar vermis with small fourth ventricle associated with callosal hypoplasia". Neuroradiology. 11 (2): 99–102. doi:10.1007/BF00345021. ISSN 0028-3940.
- ↑ Boltshauser E, Isler W (February 1977). "Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis". Neuropadiatrie. 8 (1): 57–66. doi:10.1055/s-0028-1091505. PMID 576733.
- ↑ Boltshauser, E.; Isler, W. (2008). "Joubert Syndrome: Episodic Hyperpnea, Abnormal Eye Movements, Retardation and Ataxia, Associated with Dysplasia of the Cerebellar Vermis". Neuropediatrics. 8 (01): 57–66. doi:10.1055/s-0028-1091505. ISSN 0174-304X.
- ↑ Friede RL, Boltshauser E (December 1978). "Uncommon syndromes of cerebellar vermis aplasia. I: Joubert syndrome". Dev Med Child Neurol. 20 (6): 758–63. PMID 729929.
- ↑ Friede, R. L.; Boltshauser, E. (2008). "Uncommon Syndromes of Cerebellar Vermis Aplasia. I: Joubert Syndrome". Developmental Medicine & Child Neurology. 20 (6): 758–763. doi:10.1111/j.1469-8749.1978.tb15307.x. ISSN 0012-1622.
- ↑ Al-Gazali L, Hamamy H (2014). "Consanguinity and dysmorphology in Arabs". Hum. Hered. 77 (1–4): 93–107. doi:10.1159/000360421. PMID 25060273.
- ↑ Al-Gazali L, Ali BR (May 2010). "Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE)". Hum. Mutat. 31 (5): 505–20. doi:10.1002/humu.21232. PMID 20437613.
- ↑ Valente, Enza Maria; Marsh, Sarah E.; Castori, Marco; Dixon-Salazar, Tracy; Bertini, Enrico; Al-Gazali, Lihadh; Messer, Jean; Barbot, Clara; Woods, C. Geoffrey; Boltshauser, Eugen; Al-Tawari, Asma A.; Salpietro, Carmelo D.; Kayserili, Hulya; Sztriha, L�szl�; Gribaa, Moez; Koenig, Michel; Dallapiccola, Bruno; Gleeson, Joseph G. (2005). "Distinguishing the four genetic causes of jouberts syndrome-related disorders". Annals of Neurology. 57 (4): 513–519. doi:10.1002/ana.20422. ISSN 0364-5134. replacement character in
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at position 2 (help) - ↑ Saraiva, Jorge M.; Baraitser, Michael (1992). "Joubert syndrome: A review". American Journal of Medical Genetics. 43 (4): 726–731. doi:10.1002/ajmg.1320430415. ISSN 0148-7299.
- ↑ Parisi MA (November 2009). "Clinical and molecular features of Joubert syndrome and related disorders". Am J Med Genet C Semin Med Genet. 151C (4): 326–40. doi:10.1002/ajmg.c.30229. PMC 2797758. PMID 19876931.
- ↑ Valente EM, Marsh SE, Castori M, Dixon-Salazar T, Bertini E, Al-Gazali L, Messer J, Barbot C, Woods CG, Boltshauser E, Al-Tawari AA, Salpietro CD, Kayserili H, Sztriha L, Gribaa M, Koenig M, Dallapiccola B, Gleeson JG (April 2005). "Distinguishing the four genetic causes of Jouberts syndrome-related disorders". Ann. Neurol. 57 (4): 513–9. doi:10.1002/ana.20422. PMID 15786477.
- ↑ Saar K, Al-Gazali L, Sztriha L, Rueschendorf F, Nur-E-Kamal M, Reis A, Bayoumi R (December 1999). "Homozygosity mapping in families with Joubert syndrome identifies a locus on chromosome 9q34.3 and evidence for genetic heterogeneity". Am. J. Hum. Genet. 65 (6): 1666–71. doi:10.1086/302655. PMC 1288377. PMID 10577920.
- ↑ Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO, Kayserili H, Swistun D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field SJ, Gayral S, Jacoby M, Schurmans S, Dallapiccola B, Majerus PW, Valente EM, Gleeson JG (September 2009). "Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies". Nat. Genet. 41 (9): 1032–6. doi:10.1038/ng.423. PMC 2746682. PMID 19668216.
- ↑ Jacoby M, Cox JJ, Gayral S, Hampshire DJ, Ayub M, Blockmans M, Pernot E, Kisseleva MV, Compère P, Schiffmann SN, Gergely F, Riley JH, Pérez-Morga D, Woods CG, Schurmans S (September 2009). "INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse". Nat. Genet. 41 (9): 1027–31. doi:10.1038/ng.427. PMID 19668215.
- ↑ Lagier-Tourenne C, Boltshauser E, Breivik N, Gribaa M, Bétard C, Barbot C, Koenig M (April 2004). "Homozygosity mapping of a third Joubert syndrome locus to 6q23". J. Med. Genet. 41 (4): 273–7. doi:10.1136/jmg.2003.014787. PMC 1735723. PMID 15060101.
- ↑ Valente EM, Brancati F, Silhavy JL, Castori M, Marsh SE, Barrano G, Bertini E, Boltshauser E, Zaki MS, Abdel-Aleem A, Abdel-Salam GM, Bellacchio E, Battini R, Cruse RP, Dobyns WB, Krishnamoorthy KS, Lagier-Tourenne C, Magee A, Pascual-Castroviejo I, Salpietro CD, Sarco D, Dallapiccola B, Gleeson JG (March 2006). "AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders". Ann. Neurol. 59 (3): 527–34. doi:10.1002/ana.20749. PMID 16453322.
- ↑ Tuz K, Hsiao YC, Juárez O, Shi B, Harmon EY, Phelps IG, Lennartz MR, Glass IA, Doherty D, Ferland RJ (May 2013). "The Joubert syndrome-associated missense mutation (V443D) in the Abelson-helper integration site 1 (AHI1) protein alters its localization and protein-protein interactions". J. Biol. Chem. 288 (19): 13676–94. doi:10.1074/jbc.M112.420786. PMC 3650405. PMID 23532844.
- ↑ Louie CM, Gleeson JG (October 2005). "Genetic basis of Joubert syndrome and related disorders of cerebellar development". Hum. Mol. Genet. 14 Spec No. 2: R235–42. doi:10.1093/hmg/ddi264. PMID 16244321.
- ↑ Parisi MA, Doherty D, Eckert ML, Shaw DW, Ozyurek H, Aysun S, Giray O, Al Swaid A, Al Shahwan S, Dohayan N, Bakhsh E, Indridason OS, Dobyns WB, Bennett CL, Chance PF, Glass IA (April 2006). "AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome". J. Med. Genet. 43 (4): 334–9. doi:10.1136/jmg.2005.036608. PMC 2563230. PMID 16155189.
- ↑ Dixon-Salazar T, Silhavy JL, Marsh SE, Louie CM, Scott LC, Gururaj A, Al-Gazali L, Al-Tawari AA, Kayserili H, Sztriha L, Gleeson JG (December 2004). "Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria". Am. J. Hum. Genet. 75 (6): 979–87. doi:10.1086/425985. PMC 1182159. PMID 15467982.
- ↑ Hildebrandt F, Otto E, Rensing C, Nothwang HG, Vollmer M, Adolphs J, Hanusch H, Brandis M (October 1997). "A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1". Nat. Genet. 17 (2): 149–53. doi:10.1038/ng1097-149. PMID 9326933.
- ↑ Otto E, Betz R, Rensing C, Schätzle S, Kuntzen T, Vetsi T, Imm A, Hildebrandt F (September 2000). "A deletion distinct from the classical homologous recombination of juvenile nephronophthisis type 1 (NPH1) allows exact molecular definition of deletion breakpoints". Hum. Mutat. 16 (3): 211–23. doi:10.1002/1098-1004(200009)16:3<211::AID-HUMU4>3.0.CO;2-Y. PMID 10980528.
- ↑ Tory K, Lacoste T, Burglen L, Morinière V, Boddaert N, Macher MA, Llanas B, Nivet H, Bensman A, Niaudet P, Antignac C, Salomon R, Saunier S (May 2007). "High NPHP1 and NPHP6 mutation rate in patients with Joubert syndrome and nephronophthisis: potential epistatic effect of NPHP6 and AHI1 mutations in patients with NPHP1 mutations". J. Am. Soc. Nephrol. 18 (5): 1566–75. doi:10.1681/ASN.2006101164. PMID 17409309.
- ↑ Parisi MA, Bennett CL, Eckert ML, Dobyns WB, Gleeson JG, Shaw DW, McDonald R, Eddy A, Chance PF, Glass IA (July 2004). "The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome". Am. J. Hum. Genet. 75 (1): 82–91. doi:10.1086/421846. PMC 1182011. PMID 15138899.
- ↑ Saunier S, Calado J, Benessy F, Silbermann F, Heilig R, Weissenbach J, Antignac C (March 2000). "Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis". Am. J. Hum. Genet. 66 (3): 778–89. doi:10.1086/302819. PMC 1288163. PMID 10712196.
- ↑ Konrad M, Saunier S, Heidet L, Silbermann F, Benessy F, Calado J, Le Paslier D, Broyer M, Gubler MC, Antignac C (March 1996). "Large homozygous deletions of the 2q13 region are a major cause of juvenile nephronophthisis". Hum. Mol. Genet. 5 (3): 367–71. PMID 8852662.
- ↑ Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, Dobyns WB (October 1999). "Clinical nosologic and genetic aspects of Joubert and related syndromes". J. Child Neurol. 14 (10): 660–6, discussion 669–72. doi:10.1177/088307389901401007. PMID 10511339.
- ↑ Kroes HY, van Zon PH, Fransen van de Putte D, Nelen MR, Nievelstein RJ, Wittebol-Post D, van Nieuwenhuizen O, Mancini GM, van der Knaap MS, Kwee ML, Maas SM, Cobben JM, De Nef JE, Lindhout D, Sinke RJ (2008). "DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands". Eur J Med Genet. 51 (1): 24–34. doi:10.1016/j.ejmg.2007.10.001. PMID 18054307.
- ↑ Parisi MA, Doherty D, Chance PF, Glass IA (May 2007). "Joubert syndrome (and related disorders) (OMIM 213300)". Eur. J. Hum. Genet. 15 (5): 511–21. doi:10.1038/sj.ejhg.5201648. PMID 17377524.
- ↑ Kroes HY, van Zon PH, Fransen van de Putte D, Nelen MR, Nievelstein RJ, Wittebol-Post D, van Nieuwenhuizen O, Mancini GM, van der Knaap MS, Kwee ML, Maas SM, Cobben JM, De Nef JE, Lindhout D, Sinke RJ (2008). "DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands". Eur J Med Genet. 51 (1): 24–34. doi:10.1016/j.ejmg.2007.10.001. PMID 18054307.
- ↑ Bader I, Decker E, Mayr JA, Lunzer V, Koch J, Boltshauser E, Sperl W, Pietsch P, Ertl-Wagner B, Bolz H, Bergmann C, Rittinger O (August 2016). "MKS1 mutations cause Joubert syndrome with agenesis of the corpus callosum". Eur J Med Genet. 59 (8): 386–91. doi:10.1016/j.ejmg.2016.06.007. PMID 27377014.
- ↑ Kroes HY, van Zon PH, Fransen van de Putte D, Nelen MR, Nievelstein RJ, Wittebol-Post D, van Nieuwenhuizen O, Mancini GM, van der Knaap MS, Kwee ML, Maas SM, Cobben JM, De Nef JE, Lindhout D, Sinke RJ (2008). "DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands". Eur J Med Genet. 51 (1): 24–34. doi:10.1016/j.ejmg.2007.10.001. PMID 18054307.
- ↑ Parisi MA (November 2009). "Clinical and molecular features of Joubert syndrome and related disorders". Am J Med Genet C Semin Med Genet. 151C (4): 326–40. doi:10.1002/ajmg.c.30229. PMC 2797758. PMID 19876931.
- ↑ Valente EM, Brancati F, Dallapiccola B (2008). "Genotypes and phenotypes of Joubert syndrome and related disorders". Eur J Med Genet. 51 (1): 1–23. doi:10.1016/j.ejmg.2007.11.003. PMID 18164675.
- ↑ Brancati, Francesco; Dallapiccola, Bruno; Valente, Enza (2010). "Joubert Syndrome and related disorders". Orphanet Journal of Rare Diseases. 5 (1): 20. doi:10.1186/1750-1172-5-20. ISSN 1750-1172.
- ↑ Kroes HY, van Zon PH, Fransen van de Putte D, Nelen MR, Nievelstein RJ, Wittebol-Post D, van Nieuwenhuizen O, Mancini GM, van der Knaap MS, Kwee ML, Maas SM, Cobben JM, De Nef JE, Lindhout D, Sinke RJ (2008). "DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands". Eur J Med Genet. 51 (1): 24–34. doi:10.1016/j.ejmg.2007.10.001. PMID 18054307.
- ↑ Brancati F, Dallapiccola B, Valente EM (July 2010). "Joubert Syndrome and related disorders". Orphanet J Rare Dis. 5: 20. doi:10.1186/1750-1172-5-20. PMC 2913941. PMID 20615230.
- ↑ Parisi MA (November 2009). "Clinical and molecular features of Joubert syndrome and related disorders". Am J Med Genet C Semin Med Genet. 151C (4): 326–40. doi:10.1002/ajmg.c.30229. PMC 2797758. PMID 19876931.
- ↑ Barreirinho MS, Teixeira J, Moreira NC, Bastos S, Gonçalvez S, Barbot MC (2001). "[Joubert's syndrome: report of 12 cases]". Rev Neurol (in Spanish; Castilian). 32 (9): 812–7. PMID 11424029.
- ↑ Parisi MA, Doherty D, Chance PF, Glass IA (May 2007). "Joubert syndrome (and related disorders) (OMIM 213300)". Eur. J. Hum. Genet. 15 (5): 511–21. doi:10.1038/sj.ejhg.5201648. PMID 17377524.
- ↑ Barreirinho MS, Teixeira J, Moreira NC, Bastos S, Gonçalvez S, Barbot MC (2001). "[Joubert's syndrome: report of 12 cases]". Rev Neurol (in Spanish; Castilian). 32 (9): 812–7. PMID 11424029.
- ↑ Braddock SR, Henley KM, Maria BL (December 2007). "The face of Joubert syndrome: a study of dysmorphology and anthropometry". Am. J. Med. Genet. A. 143A (24): 3235–42. doi:10.1002/ajmg.a.32099. PMID 18000967.
- ↑ Brancati F, Dallapiccola B, Valente EM (July 2010). "Joubert Syndrome and related disorders". Orphanet J Rare Dis. 5: 20. doi:10.1186/1750-1172-5-20. PMC 2913941. PMID 20615230.
- ↑ Ahmed J, Ali US (July 2011). "Joubert syndrome with nephronophthisis in neurofibromatosis type 1". Saudi J Kidney Dis Transpl. 22 (4): 788–91. PMID 21743231.
- ↑ "Joubert Syndrome in Three Children in A Family: A Case Series".
- ↑ "Joubert Syndrome in Three Children in A Family: A Case Series".
- ↑ "Joubert Syndrome: Imaging Features and Illustration of a Case".
- ↑ Steinlin M, Schmid M, Landau K, Boltshauser E (August 1997). "Follow-up in children with Joubert syndrome". Neuropediatrics. 28 (4): 204–11. doi:10.1055/s-2007-973701. PMID 9309710.
- ↑ Valente EM, Brancati F, Dallapiccola B (2008). "Genotypes and phenotypes of Joubert syndrome and related disorders". Eur J Med Genet. 51 (1): 1–23. doi:10.1016/j.ejmg.2007.11.003. PMID 18164675.
- ↑ Maria BL, Boltshauser E, Palmer SC, Tran TX (September 1999). "Clinical features and revised diagnostic criteria in Joubert syndrome". J. Child Neurol. 14 (9): 583–90, discussion 590–1. doi:10.1177/088307389901400906. PMID 10488903.
- ↑ Barreirinho MS, Teixeira J, Moreira NC, Bastos S, Gonçalvez S, Barbot MC (2001). "[Joubert's syndrome: report of 12 cases]". Rev Neurol (in Spanish; Castilian). 32 (9): 812–7. PMID 11424029.
- ↑ Barreirinho MS, Teixeira J, Moreira NC, Bastos S, Gonçalvez S, Barbot MC (2001). "[Joubert's syndrome: report of 12 cases]". Rev Neurol (in Spanish; Castilian). 32 (9): 812–7. PMID 11424029.
- ↑ Saraiva JM, Baraitser M (July 1992). "Joubert syndrome: a review". Am. J. Med. Genet. 43 (4): 726–31. doi:10.1002/ajmg.1320430415. PMID 1341417.
- ↑ Parisi MA, Doherty D, Chance PF, Glass IA (May 2007). "Joubert syndrome (and related disorders) (OMIM 213300)". Eur. J. Hum. Genet. 15 (5): 511–21. doi:10.1038/sj.ejhg.5201648. PMID 17377524.
- ↑ Valente EM, Brancati F, Dallapiccola B (2008). "Genotypes and phenotypes of Joubert syndrome and related disorders". Eur J Med Genet. 51 (1): 1–23. doi:10.1016/j.ejmg.2007.11.003. PMID 18164675.
- ↑ Steinlin M, Schmid M, Landau K, Boltshauser E (August 1997). "Follow-up in children with Joubert syndrome". Neuropediatrics. 28 (4): 204–11. doi:10.1055/s-2007-973701. PMID 9309710.
- ↑ Barreirinho MS, Teixeira J, Moreira NC, Bastos S, Gonçalvez S, Barbot MC (2001). "[Joubert's syndrome: report of 12 cases]". Rev Neurol (in Spanish; Castilian). 32 (9): 812–7. PMID 11424029.
- ↑ Bader I, Decker E, Mayr JA, Lunzer V, Koch J, Boltshauser E, Sperl W, Pietsch P, Ertl-Wagner B, Bolz H, Bergmann C, Rittinger O (August 2016). "MKS1 mutations cause Joubert syndrome with agenesis of the corpus callosum". Eur J Med Genet. 59 (8): 386–91. doi:10.1016/j.ejmg.2016.06.007. PMID 27377014.
- ↑ Friede RL, Boltshauser E (December 1978). "Uncommon syndromes of cerebellar vermis aplasia. I: Joubert syndrome". Dev Med Child Neurol. 20 (6): 758–63. PMID 729929.
- ↑ Maria BL, Boltshauser E, Palmer SC, Tran TX (September 1999). "Clinical features and revised diagnostic criteria in Joubert syndrome". J. Child Neurol. 14 (9): 583–90, discussion 590–1. doi:10.1177/088307389901400906. PMID 10488903.
- ↑ Brancati F, Dallapiccola B, Valente EM (July 2010). "Joubert Syndrome and related disorders". Orphanet J Rare Dis. 5: 20. doi:10.1186/1750-1172-5-20. PMC 2913941. PMID 20615230.
- ↑ Parisi MA, Doherty D, Chance PF, Glass IA (May 2007). "Joubert syndrome (and related disorders) (OMIM 213300)". Eur. J. Hum. Genet. 15 (5): 511–21. doi:10.1038/sj.ejhg.5201648. PMID 17377524.
- ↑ Barreirinho MS, Teixeira J, Moreira NC, Bastos S, Gonçalvez S, Barbot MC (2001). "[Joubert's syndrome: report of 12 cases]". Rev Neurol (in Spanish; Castilian). 32 (9): 812–7. PMID 11424029.
- ↑ Barreirinho MS, Teixeira J, Moreira NC, Bastos S, Gonçalvez S, Barbot MC (2001). "[Joubert's syndrome: report of 12 cases]". Rev Neurol (in Spanish; Castilian). 32 (9): 812–7. PMID 11424029.
- ↑ Fennell EB, Gitten JC, Dede DE, Maria BL (September 1999). "Cognition, behavior, and development in Joubert syndrome". J. Child Neurol. 14 (9): 592–6. doi:10.1177/088307389901400907. PMID 10488904.
- ↑ Yachnis AT, Rorke LB (October 1999). "Neuropathology of Joubert syndrome". J. Child Neurol. 14 (10): 655–9, discussion 669–72. doi:10.1177/088307389901401006. PMID 10511338.
- ↑ Yachnis AT, Rorke LB (September 1999). "Cerebellar and brainstem development: an overview in relation to Joubert syndrome". J. Child Neurol. 14 (9): 570–3. doi:10.1177/088307389901400904. PMID 10488901.
- ↑ Friede RL, Boltshauser E (December 1978). "Uncommon syndromes of cerebellar vermis aplasia. I: Joubert syndrome". Dev Med Child Neurol. 20 (6): 758–63. PMID 729929.
- ↑ Maria BL, Boltshauser E, Palmer SC, Tran TX (September 1999). "Clinical features and revised diagnostic criteria in Joubert syndrome". J. Child Neurol. 14 (9): 583–90, discussion 590–1. doi:10.1177/088307389901400906. PMID 10488903.
- ↑ Ahmed J, Ali US (July 2011). "Joubert syndrome with nephronophthisis in neurofibromatosis type 1". Saudi J Kidney Dis Transpl. 22 (4): 788–91. PMID 21743231.
- ↑ "Twenty classic signs in neuroradiology: A pictorial essay".