ORPHA: 1454;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 16q12.2 | ?COACH syndrome 3 | 619113 | Autosomal recessive | 3 | RPGRIP1L | 610937 |
A number sign (#) is used with this entry because of evidence that COACH syndrome-3 (COACH3) is caused by compound heterozygous mutation in the RPGRIP1L gene (610937) on chromosome 16q12. One such patient has been reported.
Joubert syndrome-7 (JBTS7; 611560) and Meckel syndrome-5 (MKS5; 611561) 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.
Doherty et al. (2010) reported a 17-year-old boy (UW04) who presented at age 15 months with hypotonia, developmental delay, alternating hyperpnea/apnea, and oculomotor apraxia. Brain MRI at 9 months of age demonstrated the molar tooth sign. By age 5 years, he manifested ataxia and was diagnosed with chronic anemia and progressive renal insufficiency. Liver biopsy revealed mild to moderate portal fibrosis, and renal biopsy showed marked interstitial fibrosis and inflammation with tubular atrophy, consistent with nephronophthisis. Peritoneal dialysis was required, followed by renal transplantation at age 6 years. The patient had a 16-year-old brother with a similar history who required kidney transplantation but had no clinical evidence of liver disease.
The transmission pattern of COACH3 in a patient reported by Doherty et al. (2010) was consistent with autosomal recessive inheritance.
In a 17-year-old boy (UW04) with COACH3, Doherty et al. (2010) identified compound heterozygous mutations in the RPGRIP1L gene (R805X, 610937.0011; S659P, 610937.0012). The mutations were also present in his similarly affected brother who had no clinical evidence of liver disease at age 16 years.
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]
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]