MCID: CCH002
MIFTS: 50

Coach Syndrome

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Liver diseases, Fetal diseases

Aliases & Classifications for Coach Syndrome

MalaCards integrated aliases for Coach Syndrome:

Name: Coach Syndrome 57 53 59 75 37 29 13 6 40 73
Joubert Syndrome with Congenital Hepatic Fibrosis 57 53 59 75
Cerebellar Vermis Hypoplasia-Oligophrenia-Congenital Ataxia-Coloboma-Hepatic Fibrosis 53 59
Joubert Syndrome with Hepatic Defect 53 59
Gentile Syndrome 53 59
Js-H 53 59
Cerebellar Vermis Hypo/aplasia, Oligophrenia, Congenital Ataxia, Ocular Coloboma, and Hepatic Fibrosis 57
Cerebellar Vermis Hypo/aplasia Oligophrenia Congenital Ataxia Ocular Coloboma and Hepatic Fibrosis 75
Cerebellar Vermis Hypo/aplasia, Oligophrenia, Ataxia Congenital, Coloboma, and Hepatic Fibrosis 53
Coachs 75

Characteristics:

Orphanet epidemiological data:

59
joubert syndrome with hepatic defect
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
genetic heterogeneity
liver involvement can range from mild to severe
renal involvement and coloboma may not be present
considered to be part of the spectrum of joubert syndrome and meckel syndrome


HPO:

32
coach syndrome:
Onset and clinical course infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Coach Syndrome

OMIM : 57 COACH syndrome is an autosomal recessive disorder characterized by mental retardation, 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). (216360)

MalaCards based summary : Coach Syndrome, also known as joubert syndrome with congenital hepatic fibrosis, is related to congenital hepatic fibrosis and joubert syndrome 1, and has symptoms including ataxia An important gene associated with Coach Syndrome is TMEM67 (Transmembrane Protein 67), and among its related pathways/superpathways are Regulation of PLK1 Activity at G2/M Transition and Organelle biogenesis and maintenance. The drug Liver Extracts has been mentioned in the context of this disorder. Affiliated tissues include liver, eye and brain, and related phenotypes are macrocephaly and low-set ears

UniProtKB/Swiss-Prot : 75 COACH syndrome: A disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Patients present the molar tooth sign, a midbrain-hindbrain malformation pathognomonic for Joubert syndrome and related disorders. Other features, such as coloboma and renal cysts, may be variable.

NIH Rare Diseases : 53 COACH syndromeis a condition that mainly affects the brain and liver.  Most individuals with COACH syndrome have mental retardation, liver problems (fibrosis), and difficulty with movement (ataxia).  Some may also have an abnormality of the eye (called a coloboma) or abnormal eye movements (such as nystagmus).  This condition is inherited in an autosomal recessive manner; 70% of cases are thought to be caused by mutations in the TMEM67 gene.  COACH syndrome is considered a rare form of another condition, Joubert syndrome.  

Wikipedia : 76 COACH syndrome is a rare recessive genetic disease. The name is an acronym of the defining signs:... more...

Related Diseases for Coach Syndrome

Graphical network of the top 20 diseases related to Coach Syndrome:



Diseases related to Coach Syndrome

Symptoms & Phenotypes for Coach Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
nystagmus
oculomotor apraxia
ocular coloboma

AbdomenSpleen:
splenomegaly

Genitourinary Kidneys:
nephronophthisis
renal failure
medullary cystic renal disease

Laboratory Abnormalities:
abnormal liver enzymes

Neurologic Central Nervous System:
ataxia
hyperreflexia
cerebellar vermis hypoplasia
hypotonia
mental retardation
more
Abdomen Liver:
hepatomegaly
portal hypertension
cirrhosis
ductal plate malformation
hepatic fibrosis, congenital
more
Growth Other:
poor growth

Respiratory:
abnormal breathing pattern


Clinical features from OMIM:

216360

Human phenotypes related to Coach Syndrome:

59 32 (show top 50) (show all 62)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000256
2 low-set ears 59 32 occasional (7.5%) Occasional (29-5%) HP:0000369
3 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000238
4 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
5 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
6 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
7 ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001251
8 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
9 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
10 tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0001337
11 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
12 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
13 inguinal hernia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000023
14 splenomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001744
15 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
16 anteverted nares 59 32 occasional (7.5%) Occasional (29-5%) HP:0000463
17 visual impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000505
18 feeding difficulties in infancy 59 32 frequent (33%) Frequent (79-30%) HP:0008872
19 renal insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0000083
20 nephropathy 59 32 frequent (33%) Frequent (79-30%) HP:0000112
21 portal hypertension 59 32 occasional (7.5%) Occasional (29-5%) HP:0001409
22 strabismus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000486
23 biparietal narrowing 59 32 frequent (33%) Frequent (79-30%) HP:0004422
24 elevated hepatic transaminases 59 32 hallmark (90%) Very frequent (99-80%) HP:0002910
25 cirrhosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001394
26 apnea 59 32 hallmark (90%) Very frequent (99-80%) HP:0002104
27 abnormality of neuronal migration 59 32 occasional (7.5%) Occasional (29-5%) HP:0002269
28 aplasia/hypoplasia of the cerebellum 59 32 hallmark (90%) Very frequent (99-80%) HP:0007360
29 prominent nasal bridge 59 32 occasional (7.5%) Occasional (29-5%) HP:0000426
30 chorioretinal coloboma 59 32 frequent (33%) Frequent (79-30%) HP:0000567
31 intellectual disability, moderate 59 32 hallmark (90%) Very frequent (99-80%) HP:0002342
32 multicystic kidney dysplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000003
33 congenital hepatic fibrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002612
34 long face 59 32 frequent (33%) Frequent (79-30%) HP:0000276
35 highly arched eyebrow 59 32 occasional (7.5%) Occasional (29-5%) HP:0002553
36 iris coloboma 59 32 frequent (33%) Frequent (79-30%) HP:0000612
37 optic nerve coloboma 59 32 frequent (33%) Frequent (79-30%) HP:0000588
38 aplasia/hypoplasia of the corpus callosum 59 32 occasional (7.5%) Occasional (29-5%) HP:0007370
39 postaxial hand polydactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001162
40 oral cleft 59 32 occasional (7.5%) Occasional (29-5%) HP:0000202
41 oculomotor apraxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000657
42 abnormality of the hypothalamus-pituitary axis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000864
43 cerebellar vermis hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001320
44 neoplasm of the liver 59 32 occasional (7.5%) Occasional (29-5%) HP:0002896
45 occipital encephalocele 59 32 occasional (7.5%) Occasional (29-5%) HP:0002085
46 chronic hepatic failure 59 32 occasional (7.5%) Occasional (29-5%) HP:0100626
47 intrahepatic biliary atresia 59 32 hallmark (90%) Very frequent (99-80%) HP:0005248
48 hypertelorism 32 HP:0000316
49 spasticity 32 HP:0001257
50 global developmental delay 32 HP:0001263

UMLS symptoms related to Coach Syndrome:


ataxia

MGI Mouse Phenotypes related to Coach Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.71 CC2D2A INPP5E RPGRIP1L TMEM67
2 digestive/alimentary MP:0005381 9.67 CC2D2A INPP5E RPGRIP1L TMEM67
3 embryo MP:0005380 9.62 CC2D2A INPP5E RPGRIP1L TMEM67
4 growth/size/body region MP:0005378 9.56 CC2D2A INPP5E RPGRIP1L TMEM67
5 limbs/digits/tail MP:0005371 9.46 CC2D2A INPP5E RPGRIP1L TMEM67
6 nervous system MP:0003631 9.26 TMEM67 CC2D2A INPP5E RPGRIP1L
7 renal/urinary system MP:0005367 8.92 CC2D2A INPP5E RPGRIP1L TMEM67

Drugs & Therapeutics for Coach Syndrome

Drugs for Coach Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Clinical and Molecular Investigations Into Ciliopathies Active, not recruiting NCT00068224

Search NIH Clinical Center for Coach Syndrome

Genetic Tests for Coach Syndrome

Genetic tests related to Coach Syndrome:

# Genetic test Affiliating Genes
1 Coach Syndrome 29 CC2D2A RPGRIP1L TMEM67

Anatomical Context for Coach Syndrome

MalaCards organs/tissues related to Coach Syndrome:

41
Liver, Eye, Brain, Kidney, Pituitary, Hypothalamus, Cerebellum

Publications for Coach Syndrome

Articles related to Coach Syndrome:

(show all 17)
# Title Authors Year
1
Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome. ( 28860541 )
2017
2
Coach syndrome: the first case from Turkey. ( 25698282 )
2015
3
Molar Tooth Sign with Deranged Liver Function Tests: An Indian Case with COACH Syndrome. ( 26075130 )
2015
4
Dealing with congenital hepatic fibrosis? Remember COACH syndrome. ( 26183508 )
2014
5
COACH syndrome: an unusual cause of neonatal cholestasis. ( 21237470 )
2011
6
Pulmonary embolism after long duration rail travel: economy class syndrome or rail coach syndrome. ( 22315757 )
2011
7
Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis). ( 19574260 )
2010
8
MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement. ( 19058225 )
2009
9
The first Japanese case of COACH syndrome. ( 19261004 )
2009
10
Successful combined liver and kidney transplant for COACH syndrome and 5-yr follow-up. ( 16313315 )
2005
11
COACH syndrome associated with multifocal liver tumors. ( 12385458 )
2002
12
Early detection of severe cholestatic hepatopathy in COACH syndrome. ( 12210305 )
2002
13
Hepatic insufficiency and liver transplantation in a patient with COACH syndrome. ( 12390436 )
2002
14
Cerebello-oculo-renal syndromes including Arima, Senior-LAPken and COACH syndromes: more than just variants of Joubert syndrome. ( 10508989 )
1999
15
Imaging findings in COACH syndrome. ( 9530063 )
1998
16
Renal insufficiency is a component of COACH syndrome. ( 8669436 )
1996
17
COACH syndrome: report of two brothers with congenital hepatic fibrosis, cerebellar vermis hypoplasia, oligophrenia, ataxia, and mental retardation. ( 8862632 )
1996

Variations for Coach Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Coach Syndrome:

75 (show all 18)
# Symbol AA change Variation ID SNP ID
1 CC2D2A p.Arg1528Cys VAR_055323 rs118204052
2 CC2D2A p.Thr1116Met VAR_063804 rs267606709
3 RPGRIP1L p.Ser659Pro VAR_063805 rs267607020
4 TMEM67 p.Tyr513Cys VAR_031987 rs137853107
5 TMEM67 p.Met252Thr VAR_062313 rs202149403
6 TMEM67 p.Arg440Gln VAR_062318 rs386834182
7 TMEM67 p.Cys615Arg VAR_062319 rs201893408
8 TMEM67 p.Pro130Arg VAR_063786 rs863225226
9 TMEM67 p.Asn242Thr VAR_063788
10 TMEM67 p.Leu349Ser VAR_063790 rs386834180
11 TMEM67 p.Pro358Leu VAR_063791 rs863225232
12 TMEM67 p.Thr372Lys VAR_063792 rs863225235
13 TMEM67 p.Phe590Ser VAR_063796 rs267607115
14 TMEM67 p.Ser728Gly VAR_063798
15 TMEM67 p.His782Arg VAR_063799 rs777137476
16 TMEM67 p.Arg820Ser VAR_063800
17 TMEM67 p.Ile833Thr VAR_063801 rs267607119
18 TMEM67 p.Gly132Ala VAR_079632

ClinVar genetic disease variations for Coach Syndrome:

6
(show all 30)
# Gene Variation Type Significance SNP ID Assembly Location
1 CC2D2A NM_001080522.2(CC2D2A): c.3145C> T (p.Arg1049Ter) single nucleotide variant Pathogenic rs386833750 GRCh37 Chromosome 4, 15565108: 15565108
2 CC2D2A NM_001080522.2(CC2D2A): c.3145C> T (p.Arg1049Ter) single nucleotide variant Pathogenic rs386833750 GRCh38 Chromosome 4, 15563485: 15563485
3 CC2D2A NM_001080522.2(CC2D2A): c.3347C> T (p.Thr1116Met) single nucleotide variant Pathogenic rs267606709 GRCh37 Chromosome 4, 15569358: 15569358
4 CC2D2A NM_001080522.2(CC2D2A): c.3347C> T (p.Thr1116Met) single nucleotide variant Pathogenic rs267606709 GRCh38 Chromosome 4, 15567735: 15567735
5 RPGRIP1L NM_015272.4(RPGRIP1L): c.2413C> T (p.Arg805Ter) single nucleotide variant Pathogenic rs145665129 GRCh37 Chromosome 16, 53679807: 53679807
6 RPGRIP1L NM_015272.4(RPGRIP1L): c.2413C> T (p.Arg805Ter) single nucleotide variant Pathogenic rs145665129 GRCh38 Chromosome 16, 53645895: 53645895
7 RPGRIP1L NM_015272.4(RPGRIP1L): c.1975T> C (p.Ser659Pro) single nucleotide variant Pathogenic rs267607020 GRCh37 Chromosome 16, 53686624: 53686624
8 RPGRIP1L NM_015272.4(RPGRIP1L): c.1975T> C (p.Ser659Pro) single nucleotide variant Pathogenic rs267607020 GRCh38 Chromosome 16, 53652712: 53652712
9 TMEM67 NM_153704.5(TMEM67): c.1538A> G (p.Tyr513Cys) single nucleotide variant Pathogenic rs137853107 GRCh37 Chromosome 8, 94803510: 94803510
10 TMEM67 NM_153704.5(TMEM67): c.1538A> G (p.Tyr513Cys) single nucleotide variant Pathogenic rs137853107 GRCh38 Chromosome 8, 93791282: 93791282
11 TMEM67 NM_153704.5(TMEM67): c.1961-2A> C single nucleotide variant Pathogenic rs758948621 GRCh38 Chromosome 8, 93797329: 93797329
12 TMEM67 NM_153704.5(TMEM67): c.1961-2A> C single nucleotide variant Pathogenic rs758948621 GRCh37 Chromosome 8, 94809557: 94809557
13 TMEM67 NM_153704.5(TMEM67): c.2498T> C (p.Ile833Thr) single nucleotide variant Pathogenic rs267607119 GRCh37 Chromosome 8, 94821126: 94821126
14 TMEM67 NM_153704.5(TMEM67): c.2498T> C (p.Ile833Thr) single nucleotide variant Pathogenic rs267607119 GRCh38 Chromosome 8, 93808898: 93808898
15 TMEM67 NM_153704.5(TMEM67): c.2556+1G> T single nucleotide variant Pathogenic rs786200867 GRCh37 Chromosome 8, 94821185: 94821185
16 TMEM67 NM_153704.5(TMEM67): c.2556+1G> T single nucleotide variant Pathogenic rs786200867 GRCh38 Chromosome 8, 93808957: 93808957
17 TMEM67 NM_153704.5(TMEM67): c.312+5G> A single nucleotide variant Pathogenic rs786200868 GRCh37 Chromosome 8, 94768099: 94768099
18 TMEM67 NM_153704.5(TMEM67): c.312+5G> A single nucleotide variant Pathogenic rs786200868 GRCh38 Chromosome 8, 93755871: 93755871
19 TMEM67 NM_153704.5(TMEM67): c.1769T> C (p.Phe590Ser) single nucleotide variant Pathogenic rs267607115 GRCh37 Chromosome 8, 94807731: 94807731
20 TMEM67 NM_153704.5(TMEM67): c.1769T> C (p.Phe590Ser) single nucleotide variant Pathogenic rs267607115 GRCh38 Chromosome 8, 93795503: 93795503
21 TMEM67 NM_153704.5(TMEM67): c.1046T> C (p.Leu349Ser) single nucleotide variant Pathogenic/Likely pathogenic rs386834180 GRCh37 Chromosome 8, 94793953: 94793953
22 TMEM67 NM_153704.5(TMEM67): c.1046T> C (p.Leu349Ser) single nucleotide variant Pathogenic/Likely pathogenic rs386834180 GRCh38 Chromosome 8, 93781725: 93781725
23 TMEM67 NM_001142301.1(TMEM67): c.1110delA (p.Glu371Lysfs) deletion Likely pathogenic rs749435317 GRCh38 Chromosome 8, 93786287: 93786287
24 TMEM67 NM_001142301.1(TMEM67): c.1110delA (p.Glu371Lysfs) deletion Likely pathogenic rs749435317 GRCh37 Chromosome 8, 94798515: 94798515
25 CC2D2A NM_001080522.2(CC2D2A): c.3652C> T (p.Arg1218Ter) single nucleotide variant Pathogenic rs375278294 GRCh37 Chromosome 4, 15575830: 15575830
26 CC2D2A NM_001080522.2(CC2D2A): c.3652C> T (p.Arg1218Ter) single nucleotide variant Pathogenic rs375278294 GRCh38 Chromosome 4, 15574207: 15574207
27 TMEM67 NM_153704.5(TMEM67): c.439C> T (p.Gln147Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 8, 94776102: 94776102
28 TMEM67 NM_153704.5(TMEM67): c.439C> T (p.Gln147Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 8, 93763874: 93763874
29 CC2D2A NM_001080522.2(CC2D2A): c.4483G> T (p.Glu1495Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 4, 15599075: 15599075
30 CC2D2A NM_001080522.2(CC2D2A): c.4483G> T (p.Glu1495Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 4, 15597452: 15597452

Expression for Coach Syndrome

Search GEO for disease gene expression data for Coach Syndrome.

Pathways for Coach Syndrome

GO Terms for Coach Syndrome

Cellular components related to Coach Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.62 CC2D2A INPP5E RPGRIP1L TMEM67
2 cell projection GO:0042995 9.46 CC2D2A INPP5E RPGRIP1L TMEM67
3 axoneme GO:0005930 9.37 INPP5E RPGRIP1L
4 MKS complex GO:0036038 9.26 CC2D2A TMEM67
5 cilium GO:0005929 9.26 CC2D2A INPP5E RPGRIP1L TMEM67
6 ciliary transition zone GO:0035869 8.8 CC2D2A RPGRIP1L TMEM67

Biological processes related to Coach Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection organization GO:0030030 9.37 CC2D2A TMEM67
2 determination of left/right symmetry GO:0007368 9.32 CC2D2A RPGRIP1L
3 camera-type eye development GO:0043010 9.26 CC2D2A RPGRIP1L
4 non-motile cilium assembly GO:1905515 9.16 CC2D2A RPGRIP1L
5 cilium assembly GO:0060271 9.13 CC2D2A RPGRIP1L TMEM67
6 ciliary basal body-plasma membrane docking GO:0097711 8.8 CC2D2A RPGRIP1L TMEM67

Sources for Coach Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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