ORPHA: 1454;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p15.32 | COACH syndrome 2 | 619111 | Autosomal recessive | 3 | CC2D2A | 612013 |
A number sign (#) is used with this entry because of evidence that COACH syndrome-2 (COACH2) is caused by compound heterozygous mutation in the CC2D2A gene (612013) on chromosome 4p15.
Joubert syndrome-9 (JBTS9; 612285) and Meckel syndrome-6 (MKS6; 612284) are allelic disorders with overlapping phenotypes.
COACH syndrome is classically defined as Cerebellar vermis hypoplasia, Oligophrenia, Ataxia, Colobomas, and Hepatic fibrosis (Verloes and Lambotte, 1989). Brain MRI demonstrates the molar tooth sign, which is a feature of Joubert syndrome. The disorder has been described as a Joubert syndrome-related disorder with liver disease (summary by Doherty et al., 2010).
For a general phenotypic description and a discussion of genetic heterogeneity of COACH syndrome, see 216360.
Gorden et al. (2008) reported a 22-year-old woman (UW49) with agenesis of the corpus callosum, hydrocephalus, cerebellar vermis hypoplasia, abnormal eye movements, coloboma, mild renal disease, and hepatic fibrosis requiring liver transplantation at age 10 years. Gorden et al. (2008) noted that the features in the patient were reminiscent of COACH syndrome, which in some cases may be a variant representing a transitional phenotype between Joubert syndrome and Meckel syndrome. Doherty et al. (2010) reported further on this patient (UW49).
Doherty et al. (2010) reported a 3-year-old boy (UW67) with abnormal respiratory control, molar tooth sign on brain MRI, elevated liver enzymes, congenital hepatic fibrosis, impaired intellectual development, and echogenic kidneys with hypertension.
The transmission pattern of COACH2 in the family reported by Gorden et al. (2008) was consistent with autosomal recessive inheritance.
In a 22-year-old woman (UW49) with features of Joubert syndrome and hepatic fibrosis requiring liver transplantation at age 10 years, Gorden et al. (2008) identified compound heterozygous mutations in the CC2D2A gene (612013.0004 and 612013.0006).
In a 3-year-old boy (UW67) with COACH2, Doherty et al. (2010) identified compound heterozygous mutations in the CC2D2A gene (612013.0007 and 612013.0008).
Doherty, D., Parisi, M. A., Finn, L. S., Gunay-Aygun, M., Al-Mateen, M., Bates, D., Clericuzio, C., Demir, H., Dorschner, M., van Essen, A. J., Gahl, W. A., Gentile, M., and 11 others. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis). J. Med. Genet. 47: 8-21, 2010. [PubMed: 19574260] [Full Text: https://doi.org/10.1136/jmg.2009.067249]
Gorden, N. T., Arts, H. H., Parisi, M. A., Coene, K. L. M., Letteboer, S. J. F., van Beersum, S. E. C., Mans, D. A., Hikida, A., Eckert, M., Knutzen, D., Alswaid, A. F., Ozyurek, H., and 23 others. CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. Am. J. Hum. Genet. 83: 559-571, 2008. [PubMed: 18950740] [Full Text: https://doi.org/10.1016/j.ajhg.2008.10.002]
Verloes, A., Lambotte, C. Further delineation of a syndrome of cerebellar vermis hypo/aplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis. Am. J. Med. Genet. 32: 227-232, 1989. [PubMed: 2929661] [Full Text: https://doi.org/10.1002/ajmg.1320320217]