Joubert syndrome with hepatic defect

General Information (adopted from Orphanet):

Synonyms, Signs: CEREBELLAR VERMIS HYPO/APLASIA, OLIGOPHRENIA, CONGENITAL ATAXIA, OCULAR COLOBOMA, AND HEPATIC FIBROSIS
JS-H
Cerebellar vermis hypoplasia - oligophrenia - congenital ataxia - coloboma - hepatic fibrosis
Gentile syndrome
joubert syndrome with congenital hepatic fibrosis
COACH syndrome
Number of Symptoms 75
OrphanetNr: 1454
OMIM Id: 216360
ICD-10: K74.0
Q04.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 8 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare genetic disease
Genetic syndrome with a cerebellar malformation as major feature
 -Rare genetic disease
Joubert syndrome and related disorders
 -Rare eye disease
 -Rare genetic disease
 -Rare neurologic disease
Multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare developmental defect during embryogenesis
Syndrome with a cerebellar malformation as major feature
 -Rare developmental defect during embryogenesis
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000083) Renal insufficiency Occasional [Orphanet] 232 / 7739
2
 (HPO:0000107) Renal cyst Occasional [Orphanet] 126 / 7739
3
 (HPO:0000112) Nephropathy Frequent [Orphanet] 92 / 7739
4
 (HPO:0008659) Multiple small medullary renal cysts 4 / 7739
5
 (HPO:0000090) Nephronophthisis 42 / 7739
6
 (HPO:0010285) Oral synechia Occasional [Orphanet] 31 / 7739
7
 (HPO:0002085) Occipital encephalocele 20 / 7739
8
 (HPO:0000426) Prominent nasal bridge Occasional [Orphanet] 121 / 7739
9
 (HPO:0000316) Hypertelorism 644 / 7739
10
 (HPO:0000202) Oral cleft Occasional [Orphanet] 120 / 7739
11
 (HPO:0002084) Encephalocele Occasional [Orphanet] 70 / 7739
12
 (HPO:0000276) Long face Frequent [Orphanet] 109 / 7739
13
 (HPO:0000463) Anteverted nares Occasional [Orphanet] 305 / 7739
14
 (HPO:0000256) Macrocephaly Occasional [Orphanet] 298 / 7739
15
 (HPO:0002553) Highly arched eyebrow Occasional [Orphanet] 92 / 7739
16
 (HPO:0000311) Round face 104 / 7739
17
 (HPO:0000341) Narrow forehead Frequent [Orphanet] 96 / 7739
18
 (HPO:0000154) Wide mouth 137 / 7739
19
 (HPO:0000486) Strabismus Occasional [Orphanet] 576 / 7739
20
 (HPO:0000588) Optic nerve coloboma Frequent [Orphanet] 27 / 7739
21
 (HPO:0000612) Iris coloboma Frequent [Orphanet] 116 / 7739
22
 (HPO:0000508) Ptosis Occasional [Orphanet] 459 / 7739
23
 (HPO:0000657) Oculomotor apraxia Very frequent [Orphanet] 54 / 7739
24
 (HPO:0000639) Nystagmus Frequent [Orphanet] 555 / 7739
25
 (HPO:0000505) Visual impairment Frequent [Orphanet] 297 / 7739
26
 (HPO:0000479) Abnormality of the retina Frequent [Orphanet] 74 / 7739
27
 (HPO:0000589) Coloboma 47 / 7739
28
 (HPO:0000357) Abnormal location of ears Occasional [Orphanet] 328 / 7739
29
 (HPO:0001257) Spasticity 251 / 7739
30
 (HPO:0001347) Hyperreflexia Frequent [Orphanet] 363 / 7739
31
 (HPO:0002066) Gait ataxia Very frequent [Orphanet] 327 / 7739
32
 (HPO:0001337) Tremor Occasional [Orphanet] 200 / 7739
33
 (HPO:0001263) Global developmental delay 853 / 7739
34
 (HPO:0002342) Intellectual disability, moderate 37 / 7739
35
 (HPO:0002015) Dysphagia Frequent [Orphanet] 301 / 7739
36
 (HPO:0001249) Intellectual disability 1089 / 7739
37
 (HPO:0001251) Ataxia 413 / 7739
38
 (HPO:0001288) Gait disturbance Frequent [Orphanet] 318 / 7739
39
 (HPO:0001327) Photomyoclonic seizures 125 / 7739
40
 (HPO:0001250) Seizures Occasional [Orphanet] rare [HPO:skoehler] 1245 / 7739
41
 (HPO:0000864) Abnormality of the hypothalamus-pituitary axis Occasional [Orphanet] 23 / 7739
42
 (HPO:0002650) Scoliosis Occasional [Orphanet] 705 / 7739
43
 (HPO:0001162) Postaxial hand polydactyly Occasional [Orphanet] 119 / 7739
44
 (HPO:0001395) Hepatic fibrosis 67 / 7739
45
 (HPO:0002612) Congenital hepatic fibrosis Very frequent [Orphanet] 16 / 7739
46
 (HPO:0001394) Cirrhosis Occasional [Orphanet] 102 / 7739
47
 (HPO:0001744) Splenomegaly Occasional [Orphanet] 337 / 7739
48
 (HPO:0002240) Hepatomegaly Very frequent [Orphanet] 467 / 7739
49
 (HPO:0002910) Elevated hepatic transaminases Very frequent [Orphanet] 158 / 7739
50
 (HPO:0004299) Hernia of the abdominal wall Occasional [Orphanet] 176 / 7739
51
 (HPO:0001409) Portal hypertension Occasional [Orphanet] 39 / 7739
52
 (HPO:0100626) Chronic hepatic failure Occasional [Orphanet] 7 / 7739
53
 (HPO:0002896) Neoplasm of the liver Occasional [Orphanet] 17 / 7739
54
 (HPO:0005248) Intrahepatic biliary atresia Very frequent [Orphanet] 6 / 7739
55
 (HPO:0001510) Growth delay 295 / 7739
56
 (HPO:0002104) Apnea Very frequent [Orphanet] 106 / 7739
57
 (HPO:0002793) Abnormal pattern of respiration Very frequent [Orphanet] 26 / 7739
58
 (HPO:0001252) Muscular hypotonia Very frequent [Orphanet] 990 / 7739
59
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
60
 (HPO:0001324) Muscle weakness 859 / 7739
61
 (HPO:0010547) Muscle flaccidity 466 / 7739
62
 (HPO:0003593) Infantile onset 249 / 7739
63
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
64
 (OMIM) Bile duct dilatation 2 / 7739
65
 (OMIM) Ductal plate malformation 5 / 7739
66
 (OMIM) Abnormal breathing pattern 8 / 7739
67
 (HPO:0001425) Heterogeneous 132 / 7739
68
 (HPO:0000238) Hydrocephalus Occasional [Orphanet] 278 / 7739
69
 (HPO:0007370) Aplasia/Hypoplasia of the corpus callosum Occasional [Orphanet] 180 / 7739
70
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
71
 (HPO:0002536) Abnormal cortical gyration Occasional [Orphanet] 72 / 7739
72
 (HPO:0001320) Cerebellar vermis hypoplasia 57 / 7739
73
 (HPO:0002334) Abnormality of the cerebellar vermis Very frequent [Orphanet] 137 / 7739
74
 (HPO:0002419) Molar tooth sign on MRI 27 / 7739
75
 (OMIM) Medullary cystic renal disease 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Verloes and Lambotte (1989) described 3 affected children in 2 sibships. In 1 of the families with an affected boy and girl, the parents were consanguineous. The features were early-onset ataxia with hypo/aplastic vermis, hepatic fibrocirrhosis, slender skeleton, ...
Molecular genetics OMIM In 8 (57%) of 14 families with COACH syndrome, defined as Joubert syndrome with congenital liver fibrosis, Brancati et al. (2008) identified compound heterozygous mutations in the TMEM67 gene (see, e.g., 609884.0013-609884.0017). The clinical variability of the disorder, ...