Subscribe to RSS
DOI: 10.1055/s-0040-1721826
Three Cases of Joubert Syndrome in a Consanguineous Syrian Family and a Interesting Case of Multinational Collaboration
![](https://www.thieme-connect.de/media/10.1055-s-00029027/202302/lookinside/thumbnails/10-1055-s-0040-1721826_2000159-1.jpg)
Abstract
Joubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.
Informed Consent
Patient's parents provided the informed consent to the authors.
Publication History
Received: 27 September 2020
Accepted: 15 November 2020
Article published online:
06 January 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology 1969; 19 (09) 813-825
- 2 Boltshauser E, Isler W. Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis. Neuropadiatrie 1977; 8 (01) 57-66
- 3 Poretti A, Boltshauser E, Valente EM. The molar tooth sign is pathognomonic for Joubert syndrome!. Pediatr Neurol 2014; 50 (06) e15-e16
- 4 Maria BL, Hoang KB, Tusa RJ. et al. “Joubert syndrome” revisited: key ocular motor signs with magnetic resonance imaging correlation. J Child Neurol 1997; 12 (07) 423-430
- 5 Doherty D. Joubert syndrome: insights into brain development, cilium biology, and complex disease. Semin Pediatr Neurol 2009; 16 (03) 143-154
- 6 Saraiva JM, Baraitser M. Joubert syndrome: a review. Am J Med Genet 1992; 43 (04) 726-731
- 7 Wang SF, Kowal TJ, Ning K. et al. Review of ocular manifestations of Joubert syndrome. Genes (Basel) 2018; 9 (12) E605
- 8 Bachmann-Gagescu R, Dempsey JC, Phelps IG. et al; University of Washington Center for Mendelian Genomics. Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. J Med Genet 2015; 52 (08) 514-522
- 9 Parisi MA. The molecular genetics of Joubert syndrome and related ciliopathies: The challenges of genetic and phenotypic heterogeneity. Transl Sci Rare Dis 2019; 4 (1-2): 25-49
- 10 Parisi M, Glass I. Joubert Syndrome. Seattle: University of Washington; 2017
- 11 Bui TPH, Nguyen NT, Ngo VD. et al. Novel compound heterozygous TMEM67 variants in a Vietnamese family with Joubert syndrome: a case report. BMC Med Genet 2020; 21 (01) 18
- 12 Watson CM, Crinnion LA, Berry IR. et al. Enhanced diagnostic yield in Meckel-Gruber and Joubert syndrome through exome sequencing supplemented with split-read mapping. BMC Med Genet 2016; 17: 1 DOI: 10.1186/s12881-015-0265-z.
- 13 Yohe S, Thyagarajan B. Review of clinical next-generation sequencing. Arch Pathol Lab Med 2017; 141 (11) 1544-1557
- 14 Behjati S, Tarpey PS. What is next generation sequencing?. Arch Dis Child Educ Pract Ed 2013; 98 (06) 236-238
- 15 den Dunnen JT, Dalgleish R, Maglott DR. et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat 2016; 37 (06) 564-569
- 16 Kroes HY, Monroe GR, van der Zwaag B. et al. Joubert syndrome: genotyping a Northern European patient cohort. Eur J Hum Genet 2016; 24 (02) 214-220
- 17 Kroes HY, van Zon PH, Fransen van de Putte D. et al. DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands. Eur J Med Genet 2008; 51 (01) 24-34
- 18 Parisi MA, Doherty D, Eckert ML. et al. AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. J Med Genet 2006; 43 (04) 334-339
- 19 Valente EM, Brancati F, Silhavy JL. et al; International JSRD Study Group. AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders. Ann Neurol 2006; 59 (03) 527-534
- 20 Chafai-Elalaoui S, Chalon M, Elkhartoufi N. et al. A homozygous AHI1 gene mutation (p.Thr304AsnfsX6) in a consanguineous Moroccan family with Joubert syndrome: a case report. J Med Case Reports 2015; 9: 254 DOI: 10.1186/s13256-015-0732-3.
- 21 Valente EM, Brancati F, Dallapiccola B. Genotypes and phenotypes of Joubert syndrome and related disorders. Eur J Med Genet 2008; 51 (01) 1-23
- 22 Zhu L, Xie L. Prenatal diagnosis of Joubert syndrome: a case report and literature review. Medicine (Baltimore) 2017; 96 (51) e8626 DOI: 10.1097/md.0000000000008626.