3C syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: RTSC
Ritscher-Schinzel syndrome
Dandy-Walker-like malformation with atrioventricular septal defect
Craniocerebellocardiac dysplasia
3C syndrome
Cranio-cerebello-cardiac (3C) Syndrome [IBIS]
Number of Symptoms 88
OrphanetNr: 7
OMIM Id: 220210
ICD-10: Q87.8
UMLs: C0796137
MeSH: C535313
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 25 cases [Orphanet]
Inheritance: Autosomal recessive
11484200 [IBIS]
Age of onset: Antenatal
Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic syndrome with a Dandy-Walker malformation as major feature
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome-intellectual deficit
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Rare genetic intellectual deficit with developmental anomaly
 -Rare genetic disease
Rare intellectual deficit with developmental anomaly
 -Rare neurologic disease
Syndrome with a Dandy-Walker malformation as major feature
 -Rare developmental defect during embryogenesis
 -Rare neurologic disease

Comment:

Ritscher-Schinzel syndrome, also known as the 3C syndrome, is a rare, autosomal recessive syndrome characterized by craniofacial, cerebellar, and cardiac anomalies. A mutation in KIAA0196 (= WASHC5 = SPG8) is identified as the cause of one form of Ritscher-Schinzel/3C syndrome in a Canadian cohort (PMID:24065355). A missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome (PMID:24916641). Strumpellin, the product of KIAA0196, is a 134 kDa (1159 amino acid) glycoprotein that is highly conserved (from plants to humans) and ubiquitously expressed. A previous report identified three KIAA0196 missense mutations (c.1411A>G, N471D; c.1857G>C, L619F; c.1876G>T, V626F) underlying an autosomal dominant spastic paraplegia (SPG8) (PMID:24065355).

Symptom Information: Sort by abundance 

1
 (HPO:0000316) Hypertelorism Very frequent [Orphanet] 11484200 IBIS 644 / 7739
2
 (HPO:0000612) Iris coloboma Occasional [Orphanet] 11484200 IBIS 116 / 7739
3
 (HPO:0000479) Abnormality of the retina Occasional [Orphanet] 11484200 IBIS 74 / 7739
4
 (HPO:0000480) Retinal coloboma 11484200 IBIS 16 / 7739
5
 (HPO:0000589) Coloboma 11484200 IBIS 47 / 7739
6
 (HPO:0000501) Glaucoma Occasional [Orphanet] 11484200 IBIS 180 / 7739
7
 (HPO:0008751) Laryngeal cleft 11484200 IBIS 5 / 7739
8
 (HPO:0004322) Short stature Frequent [Orphanet] 10528249 IBIS 1232 / 7739
9
 (HPO:0004325) Decreased body weight Occasional [Orphanet] 11484200 IBIS 492 / 7739
10
 (HPO:0001508) Failure to thrive 11484200 IBIS 454 / 7739
11
 (HPO:0000824) Growth hormone deficiency 11484200 IBIS 56 / 7739
12
 (HPO:0008207) Primary adrenal insufficiency Occasional [Orphanet] 11484200 IBIS 26 / 7739
13
 (HPO:0001252) Muscular hypotonia Very frequent [Orphanet] 11484200 IBIS 990 / 7739
14
 (HPO:0008947) Infantile muscular hypotonia 11484200 IBIS 482 / 7739
15
 (HPO:0011442) Abnormality of central motor function Frequent [Orphanet] 11484200 IBIS 76 / 7739
16
 (HPO:0002194) Delayed gross motor development 11484200 IBIS 37 / 7739
17
 (HPO:0002167) Neurological speech impairment Very frequent [Orphanet] 11484200 IBIS 308 / 7739
18
 (HPO:0001195) Single umbilical artery Occasional [Orphanet] 11484200 IBIS 23 / 7739
19
 (HPO:0001511) Intrauterine growth retardation 11484200 IBIS 358 / 7739
20
 (HPO:0004209) Clinodactyly of the 5th finger 11484200 IBIS 288 / 7739
21
 (HPO:0001770) Toe syndactyly 11484200 IBIS 149 / 7739
22
 (HPO:0010442) Polydactyly 11484200 IBIS 69 / 7739
23
 (HPO:0001156) Brachydactyly syndrome 11484200 IBIS 180 / 7739
24
 (HPO:0001159) Syndactyly 11484200 IBIS 140 / 7739
25
 (HPO:0001385) Hip dysplasia Occasional [Orphanet] 11484200 IBIS 242 / 7739
26
 (HPO:0001762) Talipes equinovarus 25434475 IBIS 309 / 7739
27
 (HPO:0000347) Micrognathia 11484200 IBIS 426 / 7739
28
 (HPO:0000248) Brachycephaly 25434475 IBIS 222 / 7739
29
 (HPO:0001357) Plagiocephaly 11484200 IBIS 106 / 7739
30
 (HPO:0007291) Posterior fossa cyst 11484200 IBIS 10 / 7739
31
 (HPO:0001305) Dandy-Walker malformation Very frequent [Orphanet] 11484200 IBIS 79 / 7739
32
 (HPO:0000256) Macrocephaly Frequent [Orphanet] 24255872 IBIS 298 / 7739
33
 (HPO:0011220) Prominent forehead 11484200 IBIS 137 / 7739
34
 (HPO:0000269) Prominent occiput Frequent [Orphanet] 11484200 IBIS 43 / 7739
35
 (HPO:0000921) Missing ribs Occasional [Orphanet] 11484200 IBIS 62 / 7739
36
 (HPO:0006709) Aplasia/Hypoplasia of the nipples Occasional [Orphanet] 11484200 IBIS 28 / 7739
37
 (HPO:0000470) Short neck Occasional [Orphanet] 11484200 IBIS 345 / 7739
38
 (HPO:0002937) Hemivertebrae 11484200 IBIS 41 / 7739
39
 (HPO:0002079) Hypoplasia of the corpus callosum 11484200 IBIS 161 / 7739
40
 (HPO:0002162) Low posterior hairline 11484200 IBIS 88 / 7739
41
 (HPO:0001231) Abnormality of the fingernails Occasional [Orphanet] 11484200 IBIS 116 / 7739
42
 (HPO:0001804) Hypoplastic fingernail 11484200 IBIS 62 / 7739
43
 (HPO:0002023) Anal atresia Occasional [Orphanet] 11484200 IBIS 135 / 7739
44
 (HPO:0001545) Anteriorly placed anus Occasional [Orphanet] 11484200 IBIS 55 / 7739
45
 (HPO:0002566) Intestinal malrotation Occasional [Orphanet] 11484200 IBIS 89 / 7739
46
 (HPO:0001537) Umbilical hernia 11484200 IBIS 206 / 7739
47
 (HPO:0000023) Inguinal hernia 11484200 IBIS 181 / 7739
48
 (HPO:0000835) Adrenal hypoplasia 11484200 IBIS 23 / 7739
49
 (HPO:0001631) Atria septal defect Frequent [Orphanet] 11484200 IBIS 274 / 7739
50
 (HPO:0001629) Ventricular septal defect Frequent [Orphanet] 11484200 IBIS 316 / 7739
51
 (HPO:0001633) Abnormality of the mitral valve Frequent [Orphanet] 11484200 IBIS 69 / 7739
52
 (HPO:0001702) Abnormality of the tricuspid valve Frequent [Orphanet] 11484200 IBIS 32 / 7739
53
 (HPO:0011662) Tricuspid atresia 11484200 IBIS 4 / 7739
54
 (HPO:0006695) Atrioventricular canal defect Frequent [Orphanet] 7573166 IBIS 27 / 7739
55
 (HPO:0001654) Abnormality of the heart valves 11484200 IBIS 49 / 7739
56
 (HPO:0001650) Aortic valve stenosis 11484200 IBIS 49 / 7739
57
 (HPO:0002119) Ventriculomegaly Frequent [Orphanet] 11484200 IBIS 253 / 7739
58
 (HPO:0002280) Enlarged cisterna magna 11484200 IBIS 12 / 7739
59
 (HPO:0001719) Double outlet right ventricle 11484200 IBIS 12 / 7739
60
 (HPO:0004383) Hypoplastic left heart Frequent [Orphanet] 11484200 IBIS 29 / 7739
61
 (HPO:0001642) Pulmonic stenosis 11484200 IBIS 89 / 7739
62
 (HPO:0001636) Tetralogy of Fallot Frequent [Orphanet] 11484200 IBIS 104 / 7739
63
 (HPO:0008736) Hypoplasia of penis 11484200 IBIS 7 / 7739
64
 (HPO:0000047) Hypospadias Occasional [Orphanet] 11484200 IBIS 250 / 7739
65
 (HPO:0000054) Micropenis Occasional [Orphanet] 11484200 IBIS 257 / 7739
66
 (HPO:0000045) Abnormality of the scrotum 11484200 IBIS 14 / 7739
67
 (HPO:0001999) Abnormal facial shape 11484200 IBIS 169 / 7739
68
 (HPO:0000494) Downslanted palpebral fissures Frequent [Orphanet] 11484200 IBIS 328 / 7739
69
 (HPO:0000174) Abnormality of the palate Frequent [Orphanet] 11484200 IBIS 298 / 7739
70
 (HPO:0000175) Cleft palate 11484200 IBIS 349 / 7739
71
 (HPO:0002705) High, narrow palate Frequent [Orphanet] 11484200 IBIS 308 / 7739
72
 (HPO:0000202) Oral cleft Occasional [Orphanet] 11484200 IBIS 120 / 7739
73
 (HPO:0005280) Depressed nasal bridge Frequent [Orphanet] 11484200 IBIS 381 / 7739
74
 (HPO:0000474) Thickened nuchal skin fold 11484200 IBIS 10 / 7739
75
 (HPO:0000357) Abnormal location of ears Frequent [Orphanet] 11484200 IBIS 328 / 7739
76
 (HPO:0000369) Low-set ears 11484200 IBIS 372 / 7739
77
 (HPO:0000957) Cafe-au-lait spot 11484200 IBIS 84 / 7739
78
 (HPO:0010946) Dilatation of the renal pelvis 11484200 IBIS 2 / 7739
79
 (HPO:0000126) Hydronephrosis 11484200 IBIS 119 / 7739
80
 (HPO:0004414) Abnormality of the pulmonary artery Frequent [Orphanet] 11484200 IBIS 50 / 7739
81
 (HPO:0002536) Abnormal cortical gyration Occasional [Orphanet] 24255872 IBIS 72 / 7739
82
 (HPO:0030680) Abnormality of cardiovascular system morphology 11484200 IBIS 355 / 7739
83
 (HPO:0002334) Abnormality of the cerebellar vermis Frequent [Orphanet] 11484200 IBIS 137 / 7739
84
 (HPO:0006817) Aplasia/Hypoplasia of the cerebellar vermis 11484200 IBIS 15 / 7739
85
 (HPO:0003819) Death in childhood 11484200 IBIS 42 / 7739
86
 (HPO:0001522) Death in infancy Frequent [Orphanet] 11484200 IBIS 275 / 7739
87
 (HPO:0000238) Hydrocephalus Frequent [Orphanet] 11484200 IBIS 278 / 7739
88
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 11484200 IBIS 949 / 7739

Associated genes:

WASHC5;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) The 3C syndrome, also known as Ritscher-Schinzel syndrome, is a developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal ...
Clinical Description OMIM Ritscher et al. (1987) reported the cases of 2 sisters who had brain malformation in the region of the posterior fossa and atrioventricular septal defect together with similar craniofacial anomalies. The craniofacial anomalies included macrocephaly, a prominent forehead ...
Molecular genetics OMIM In 11 patients with Ritscher-Schinzel syndrome from an isolated community in northern Manitoba, Canada, Elliott et al. (2013) identified a homozygous splice site mutation in the KIAA0196 gene (610657.0004). The mutation was found by homozygosity mapping followed by ...
Population genetics OMIM Marles et al. (1995) and Elliott et al. (2013) reported Ritscher-Schinzel syndrome in First Nation patients from an isolated, remote community in northern Manitoba, Canada. Eleven patients were found to carry the same homozygous splice site mutation in ...