COACH syndrome(COACH1)

MedGen UID:: 387879
•Concept ID:: C1857662
•: Disease or Syndrome

Synonyms:	Cerebellar vermis hypo/aplasia, Oligophrenia, Ataxia congenital, Coloboma, and Hepatic fibrosis; CEREBELLAR VERMIS HYPO/APLASIA, OLIGOPHRENIA, CONGENITAL ATAXIA, OCULAR COLOBOMA, AND HEPATIC FIBROSIS; COACH1; Joubert syndrome with congenital hepatic fibrosis; Joubert syndrome with hepatic defect
SNOMED CT:	Joubert syndrome with hepatic defect (721847002); Joubert syndrome with congenital hepatic fibrosis (721847002); Cerebellar vermis hypoplasia, oligophrenia, congenital ataxia, coloboma, hepatic fibrosis (721847002); COACH syndrome (721847002); Gentile syndrome (721847002); COACH (cerebellar vermis hypoplasia, oligophrenia, congenital ataxia, coloboma, hepatic fibrosis) syndrome (721847002)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Related genes: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	TMEM67, CC2D2A, RPGRIP1L

Monarch Initiative:	MONDO:0100349
OMIM®:	216360
Orphanet:	ORPHA1454

Definition

COACH syndrome is an autosomal recessive disorder characterized by impaired intellectual development, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Other features, such as coloboma and renal cysts, may be variable. COACH syndrome is considered by some to be a subtype of Joubert syndrome (JBTS; see 213300) with congenital hepatic fibrosis. Identification of liver disease in these patients is critical because some may develop complications such as portal hypertension with fatal variceal bleeding (Brancati et al., 2009; Doherty et al., 2010). Genetic Heterogeneity of COACH Syndrome Also see COACH syndrome-2 (COACH2; 619111), caused by mutation in in the CC2D2A gene (612013), and COACH syndrome-3 (COACH3; 619113), caused by mutation in the RPGRIP1L gene (610937). Most cases of COACH syndrome are caused by mutation in the TMEM67 gene. [from OMIM]

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVCOACH syndrome

Hereditary parenchymatous liver disease
- COACH syndrome

Follow this link to review classifications for COACH syndrome in Orphanet.

Professional guidelines

PubMed

Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.

Tang X, Liu C, Liu X, Chen J, Fan X, Liu J, Ma D, Cao G, Chen Z, Xu D, Zhu Y, Jiang X, Cheng L, Wu Y, Hou L, Li Y, Shao X, Zheng S, Zhang A, Zheng B, Jian S, Rong Z, Su Q, Gao X, Rao J, Shen Q, Xu H; Chinese Children Genetic Kidney Disease Database (CCGKDD); “Internet Plus” Nephrology Alliance of the National Center for Children’s Care
J Med Genet 2022 Feb;59(2):147-154. Epub 2020 Dec 15 doi: 10.1136/jmedgenet-2020-107184. PMID: 33323469

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Recent clinical studies

Etiology

Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.

Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies.

König J, Kranz B, König S, Schlingmann KP, Titieni A, Tönshoff B, Habbig S, Pape L, Häffner K, Hansen M, Büscher A, Bald M, Billing H, Schild R, Walden U, Hampel T, Staude H, Riedl M, Gretz N, Lablans M, Bergmann C, Hildebrandt F, Omran H, Konrad M; Gesellschaft für Pädiatrische Nephrologie (GPN)
Clin J Am Soc Nephrol 2017 Dec 7;12(12):1974-1983. Epub 2017 Nov 16 doi: 10.2215/CJN.01280217. PMID: 29146700 Free PMC Article

MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement.

Brancati F, Iannicelli M, Travaglini L, Mazzotta A, Bertini E, Boltshauser E, D'Arrigo S, Emma F, Fazzi E, Gallizzi R, Gentile M, Loncarevic D, Mejaski-Bosnjak V, Pantaleoni C, Rigoli L, Salpietro CD, Signorini S, Stringini GR, Verloes A, Zabloka D, Dallapiccola B, Gleeson JG, Valente EM; International JSRD Study Group
Hum Mutat 2009 Feb;30(2):E432-42. doi: 10.1002/humu.20924. PMID: 19058225 Free PMC Article

Successful combined liver and kidney transplant for COACH syndrome and 5-yr follow-up.

Uemura T, Sanchez EQ, Ikegami T, Watkins D, Narasimhan G, McKenna GJ, Chinnakotla S, Dawson S 3rd, Randall HB, Levy MF, Goldstein RM, Klintmalm GB
Clin Transplant 2005 Dec;19(6):717-20. doi: 10.1111/j.1399-0012.2005.00409.x. PMID: 16313315

Cerebello-oculo-renal syndromes including Arima, Senior-Löken and COACH syndromes: more than just variants of Joubert syndrome.

Satran D, Pierpont ME, Dobyns WB
Am J Med Genet 1999 Oct 29;86(5):459-69. PMID: 10508989

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Diagnosis

The role of liver transplantation in COACH syndrome (Joubert syndrome with congenital hepatic fibrosis): A review of the literature.

Chen L, Uchida H, Komine R, Kodama T, Nakao T, Okada N, Yanagi Y, Shimizu S, Abbas S, Fukuda A, Sakamoto S, Kasahara M
Pediatr Transplant 2024 Feb;28(1):e14640. Epub 2023 Nov 15 doi: 10.1111/petr.14640. PMID: 37965976

Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.

Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis).

Doherty D, Parisi MA, Finn LS, Gunay-Aygun M, Al-Mateen M, Bates D, Clericuzio C, Demir H, Dorschner M, van Essen AJ, Gahl WA, Gentile M, Gorden NT, Hikida A, Knutzen D, Ozyurek H, Phelps I, Rosenthal P, Verloes A, Weigand H, Chance PF, Dobyns WB, Glass IA
J Med Genet 2010 Jan;47(1):8-21. Epub 2009 Jul 1 doi: 10.1136/jmg.2009.067249. PMID: 19574260 Free PMC Article

Clinical and molecular features of Joubert syndrome and related disorders.

Parisi MA
Am J Med Genet C Semin Med Genet 2009 Nov 15;151C(4):326-40. doi: 10.1002/ajmg.c.30229. PMID: 19876931 Free PMC Article

Early detection of severe cholestatic hepatopathy in COACH syndrome.

Foell D, August C, Frosch M, Harms E, Zimmer KP
Am J Med Genet 2002 Sep 1;111(4):429-34. doi: 10.1002/ajmg.10614. PMID: 12210305

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Therapy

The role of liver transplantation in COACH syndrome (Joubert syndrome with congenital hepatic fibrosis): A review of the literature.

The triad of pruritus, xanthomas, and cholestasis: Two cases and a brief review of the literature.

Pearson HJ, Mosser JL, Jacks SK
Pediatr Dermatol 2017 Nov;34(6):e305-e308. doi: 10.1111/pde.13306. PMID: 29144045

Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome.

Lee SH, Nam TS, Li W, Kim JH, Yoon W, Choi YD, Kim KH, Cai H, Kim MJ, Kim C, Choy HE, Kim N, Chay KO, Kim MK, Choi SY
Sci Rep 2017 Aug 31;7(1):10222. doi: 10.1038/s41598-017-10652-z. PMID: 28860541 Free PMC Article

Pulmonary embolism after long duration rail travel: economy class syndrome or rail coach syndrome.

Mittal SK, Chopra S, Calton R
J Assoc Physicians India 2011 Jul;59:458-9. PMID: 22315757

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