CSCF
MCID: CRD221
MIFTS: 44

Cardiospondylocarpofacial Syndrome (CSCF)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Cardiospondylocarpofacial Syndrome

MalaCards integrated aliases for Cardiospondylocarpofacial Syndrome:

Name: Cardiospondylocarpofacial Syndrome 57 20 58 72 36 29 6
Mitral Regurgitation, Conductive Deafness, and Fusion of Cervical Vertebrae and of Carpal and Tarsal Bones 57 20 72 70
Forney Robinson Pascoe Syndrome 20 72 70
Cscf 57 72
Congenital Heart Disease, Deafness, and Skeletal Malformations 20
Mitral Regurgitation-Hearing Loss-Skeletal Anomalies Syndrome 58
Mitral Regurgitation-Deafness-Skeletal Anomalies Syndrome 58
Syndrome, Cardiospondylocarpofacial 39
Forney-Robinson-Pascoe Syndrome 58
Hearing Loss, Bilateral 44
Forney Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
cardiospondylocarpofacial syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant


HPO:

31
cardiospondylocarpofacial syndrome:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare otorhinolaryngological diseases
Developmental anomalies during embryogenesis


Summaries for Cardiospondylocarpofacial Syndrome

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 3238 Definition Cardiospondylocarpofacial syndrome is characterized by mitral insufficiency, conductive deafness, short stature, and skeletal anomalies (bony fusion involving the cervical vertebrae, the ossicles, and the carpal and tarsal bones). It has been described in three members of one family. The mode of inheritance is likely to be autosomal dominant with incomplete penetrance.

MalaCards based summary : Cardiospondylocarpofacial Syndrome, also known as mitral regurgitation, conductive deafness, and fusion of cervical vertebrae and of carpal and tarsal bones, is related to frontometaphyseal dysplasia and ear malformation. An important gene associated with Cardiospondylocarpofacial Syndrome is MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7), and among its related pathways/superpathways are MAPK signaling pathway and Salmonella infection (KEGG). The drugs Acetylcysteine and Cisplatin have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and kidney, and related phenotypes are abnormal form of the vertebral bodies and high, narrow palate

OMIM® : 57 Cardiospondylocarpofacial syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion, extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations (Le Goff et al., 2016). (157800) (Updated 05-Apr-2021)

KEGG : 36 Cardiospondylocarpofacial (CSCF) syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. It has been reported that mutations in MAP3K7, encoding TGF-beta-activated kinase 1 (TAK1), cause this disease.

UniProtKB/Swiss-Prot : 72 Cardiospondylocarpofacial syndrome: A syndrome characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. CSCF transmission pattern is consistent with autosomal dominant inheritance.

Related Diseases for Cardiospondylocarpofacial Syndrome

Diseases related to Cardiospondylocarpofacial Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 160)
# Related Disease Score Top Affiliating Genes
1 frontometaphyseal dysplasia 29.5 MAP3K7 FLNB
2 ear malformation 29.5 MAP3K7 FLNB
3 synostosis 29.4 MAP3K7 FLNB
4 deafness, autosomal recessive 88 10.3
5 deafness, autosomal dominant 1, with or without thrombocytopenia 10.1
6 earlobes, thickened, with conductive deafness from incudostapedial abnormalities 10.1
7 fibromatosis, gingival, with progressive deafness 10.1
8 deafness, autosomal recessive 1a 10.1
9 abruzzo-erickson syndrome 10.1
10 deafness, nonsyndromic sensorineural, mitochondrial 10.1
11 deafness, autosomal recessive 2 10.1
12 deafness, autosomal dominant 2a 10.1
13 deafness, autosomal dominant 4a 10.1
14 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 10.1
15 deafness, autosomal recessive 5 10.1
16 deafness, autosomal dominant 6 10.1
17 deafness, autosomal recessive 6 10.1
18 deafness, autosomal recessive 7 10.1
19 deafness, autosomal dominant 5 10.1
20 deafness, autosomal recessive 9 10.1
21 deafness, autosomal recessive 8 10.1
22 deafness, autosomal dominant 10 10.1
23 deafness, autosomal dominant 11 10.1
24 deafness, autosomal dominant 9 10.1
25 deafness, autosomal recessive 12 10.1
26 deafness, autosomal dominant 7 10.1
27 deafness, autosomal dominant 12 10.1
28 deafness, autosomal dominant 3a 10.1
29 deafness, autosomal dominant 13 10.1
30 deafness, autosomal recessive 15 10.1
31 deafness, autosomal recessive 18a 10.1
32 deafness, autosomal dominant 15 10.1
33 deafness, autosomal recessive 17 10.1
34 deafness, autosomal recessive 13 10.1
35 deafness, autosomal dominant 17 10.1
36 deafness, autosomal recessive 21 10.1
37 deafness, autosomal recessive 14 10.1
38 deafness, autosomal recessive 16 10.1
39 deafness, autosomal dominant 16 10.1
40 deafness, autosomal recessive 20 10.1
41 deafness, autosomal dominant 20 10.1
42 deafness, autosomal dominant 23 10.1
43 deafness, autosomal recessive 26 10.1
44 deafness, autosomal dominant 25 10.1
45 deafness, autosomal recessive 27 10.1
46 deafness, autosomal dominant 18 10.1
47 deafness, autosomal dominant 24 10.1
48 deafness, autosomal dominant 22 10.1
49 deafness, autosomal dominant 30 10.1
50 deafness, autosomal dominant 36 10.1

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



Diseases related to Cardiospondylocarpofacial Syndrome

Symptoms & Phenotypes for Cardiospondylocarpofacial Syndrome

Human phenotypes related to Cardiospondylocarpofacial Syndrome:

58 31 (show all 43)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal form of the vertebral bodies 58 31 hallmark (90%) Very frequent (99-80%) HP:0003312
2 high, narrow palate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002705
3 mitral valve prolapse 58 31 hallmark (90%) Very frequent (99-80%) HP:0001634
4 mitral regurgitation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001653
5 conductive hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000405
6 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
7 synostosis of carpal bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0005048
8 short palm 58 31 hallmark (90%) Very frequent (99-80%) HP:0004279
9 severe short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003510
10 misalignment of teeth 58 31 frequent (33%) Frequent (79-30%) HP:0000692
11 failure of eruption of permanent teeth 58 31 frequent (33%) Frequent (79-30%) HP:0006352
12 horseshoe kidney 31 occasional (7.5%) HP:0000085
13 failure to thrive 31 HP:0001508
14 scoliosis 31 HP:0002650
15 delayed skeletal maturation 31 HP:0002750
16 hypertelorism 31 HP:0000316
17 abnormality of the dentition 31 HP:0000164
18 wide nasal bridge 31 HP:0000431
19 anteverted nares 31 HP:0000463
20 short stature 31 HP:0004322
21 gastroesophageal reflux 31 HP:0002020
22 full cheeks 31 HP:0000293
23 strabismus 31 HP:0000486
24 recurrent otitis media 31 HP:0000403
25 joint laxity 31 HP:0001388
26 upslanted palpebral fissure 31 HP:0000582
27 vesicoureteral reflux 31 HP:0000076
28 abnormality of the eye 31 HP:0000478
29 long philtrum 31 HP:0000343
30 telecanthus 31 HP:0000506
31 rib fusion 31 HP:0000902
32 freckling 31 HP:0001480
33 decreased testicular size 31 HP:0008734
34 congenital sensorineural hearing impairment 31 HP:0008527
35 short foot 31 HP:0001773
36 cone-shaped epiphysis 31 HP:0010579
37 tarsal synostosis 31 HP:0008368
38 feeding difficulties 31 HP:0011968
39 posteriorly rotated ears 31 HP:0000358
40 fused cervical vertebrae 31 HP:0002949
41 carpal synostosis 31 HP:0009702
42 synostosis of carpals/tarsals 31 HP:0100266
43 pseudoepiphyses 31 HP:0010584

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth Other:
failure to thrive

Head And Neck Eyes:
hypertelorism
strabismus
upslanting palpebral fissures
dystopia canthorum
peri/supraorbital fullness

Abdomen Gastrointestinal:
gastroesophageal reflux
feeding difficulties since birth
oropharyngeal difficulties

Head And Neck Ears:
recurrent otitis media
long philtrum
posteriorly rotated ears
conductive deafness, bilateral
inner ear malformation

Skeletal Hands:
brachydactyly
pseudoepiphyses
cone-shaped epiphyses
carpal fusion
poorly modeled phalanges

Skeletal Feet:
pseudoepiphyses
tarsal fusion
small feet

Genitourinary Kidneys:
horseshoe kidney (rare)

Growth Height:
small stature

Skeletal Limbs:
short extremities

Skeletal Spine:
scoliosis
posterior cervical vertebral fusion
dorsal spine synostosis

Head And Neck Nose:
anteverted nares
broad nasal bridge

Head And Neck Face:
full cheeks
hypotonic face

Skeletal:
joint laxity
delayed bone age

Genitourinary Bladder:
vesicoureteral reflux

Head And Neck Teeth:
dental anomalies

Genitourinary Internal Genitalia Male:
small testes
right-sided ectopic testis

Cardiovascular Heart:
septal defect
valve dysplasia

Clinical features from OMIM®:

157800 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Cardiospondylocarpofacial Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-151 9.23 FLNB
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-156 9.23 MAP3K7
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.23 FLNB
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-184 9.23 FLNB
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-212 9.23 MAP3K7
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 9.23 MAP3K7
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-51 9.23 MAP3K7
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-92 9.23 MAP3K7

Drugs & Therapeutics for Cardiospondylocarpofacial Syndrome

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

(show all 16)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcysteine Approved, Investigational Phase 4 616-91-1 12035
2
Cisplatin Approved Phase 4 15663-27-1 84093 441203 2767
3
Cysteine Approved, Nutraceutical Phase 4 52-90-4 5862
4 Antidotes Phase 4
5 Respiratory System Agents Phase 4
6 Pharmaceutical Solutions Phase 4
7 Antioxidants Phase 4
8 Expectorants Phase 4
9 Anti-Infective Agents Phase 4
10 N-monoacetylcystine Phase 4
11 Antiviral Agents Phase 4
12 Protective Agents Phase 4
13
Silver sulfadiazine Approved, Vet_approved 22199-08-2 441244
14
Dexamethasone Approved, Investigational, Vet_approved 50-02-2 5743
15
Dexamethasone acetate Approved, Investigational, Vet_approved 1177-87-3
16 Anesthetics

Interventional clinical trials:

(show all 35)
# Name Status NCT ID Phase Drugs
1 Clinical Trial: Intratympanic Injection of N-acetylcysteine for Protection of Cisplatin-induced Ototoxicity Recruiting NCT04226456 Phase 4 N-acetyl cysteine
2 Effectiveness of NECTEC Model, Body-worn, Digital Hearing Aids and Cost of Screening and Hearing Aids Service in Elders Unknown status NCT01902914 Phase 1, Phase 2
3 Early Communication Intervention for Toddlers With Hearing Loss Recruiting NCT03803943 Phase 2
4 Designing a Randomised Controlled Trial to Examine the Benefit of Bilateral Cochlear Implantation Compared With Unilateral Cochlear Implantation in Adults With Severe to Profound Deafness Unknown status NCT03287700
5 Middle Ear Implant With MET V for Mixed Hearing Loss Unknown status NCT01529333
6 Implantation With the Cochlear Nucleus® CI532 Implant - Early Experience Study Completed NCT02755935
7 Structured Post Market Clinical Follow-up (PMCF) to Evaluate the Quality of a New Hearing Aid Product Generation. Completed NCT02298452
8 Quality Control of CE-Certified Phonak Hearing Aids - 2017_13 Completed NCT03131557
9 Quality Control of CE-Certified Phonak Hearing Aids - 2016_37 Completed NCT03108768
10 Evaluation of the eAdjust Application to Provide Benefits in Users of Smartphone-connected Hearing Aids Completed NCT03674086
11 Evaluation of the Impact of Coding the Fine Structure of the Sound on the Musical Perception in New Cochlear Implanted Subjects. Prospective Randomized Crossover Study. Completed NCT03993899
12 A Comparison of Conventional Hearing Aid Processing (CP) and Non-linear Frequency Compression (NLFC) Processing in Adult Patients With and Without Cochlear Dead Regions Who Have a Moderate to Severe Sensorineural Hearing Loss. Completed NCT04145661
13 Clinical Investigation of New CI Delivery Models in an Adult Nucleus CI Population Completed NCT03304106
14 Quality Control of CE-Certified Phonak Hearing Aids - 2017_27 Completed NCT03253003
15 Short-Term Pediatric Acclimatization to Adaptive Hearing Aid Technology Completed NCT04469946
16 Iowa/Nucleus 10/10 mm and Nucleus Freedom Cochlear Implants Implanted Bilaterally in Children Ages 12-24 Months Completed NCT00594061
17 Pilot Study of the Feasibility and Efficacy of Working Memory Training in Children With Cochlear Implants Completed NCT00763243
18 Evaluation of the Benefits of Bilateral Fitting in Bone-anchored Hearing System Users Completed NCT04006132
19 Auditory Brainstem Implant (ABI) in Children With No Cochleae or Auditory Nerves Recruiting NCT02310399
20 Study of Auditory Performance on Postoperative Prosodic Tests in Subjects Implanted With a MED-EL Cochlear Implant and Using a FineHearing Strategy. Prospective Longitudinal Multicentric Study Recruiting NCT03694704
21 Feasibility Study: A Totally Implantable Cochlear Implant (Mi2000) for Electrical Stimulation of the Auditory Pathway of Adults With Severe to Profound Sensorineural Hearing Loss Recruiting NCT04571333
22 The BCI 602 BONEBRIDGE Post-Market Clinical Follow-up Study Recruiting NCT04427033
23 Iowa Cochlear Implant Clinical Research Center Hybrid L24 and Standard Cochlear Implants in Profoundly Deaf Infants Recruiting NCT03156465
24 Assessing Listening Effort at Different Signal-to-noise Ratios in Bone-anchored Users Recruiting NCT04242940
25 Investigating Hearing With Ponto 3 SuperPower, a Bone Anchored Hearing Aid - Investigating Hear Recruiting NCT04803279
26 Clinical Evaluation of Outcomes With Hearing Aid Parameters Designed for Adults With Severe-profound Hearing Loss and Unilateral Cochlear Implants in Bimodal (Cochlear Implant and Contralateral Hearing Instrument), CROS (Contralateral Routing of Signals) and Bilateral Amplification Strategies Recruiting NCT04222296
27 Hearing Loss in Older Adults: A Randomized Controlled Trial of Immediate Versus Delayed Cochlear Implantation. Enrolling by invitation NCT03382769
28 The Efficacy of a Minimally Invasive Direct Cochlear Access Via the HEARO Procedure Not yet recruiting NCT04777565
29 Evaluation of New Custom Made Hearing Product Technology and Shell Modification Not yet recruiting NCT02545569
30 Study of Musical Perception and Post-operative Auditory Performance as a Function of the Depth of Stimulation in Subjects Implanted With a MED-EL Cochlear Implant and Using a FineHearing Strategy Single-center Randomized Cross-over Study Not yet recruiting NCT04591093
31 Cochlear Implant With Dexamethasone Eluting Electrode Array (The CI-DEX Study): Pivotal Study Not yet recruiting NCT04750642
32 Clinical Utility of Residual Hearing in the Cochlear Implant Ear Not yet recruiting NCT04707885
33 An Evidence Based Delivery Model of Care for Newly Implanted Adult CI Recipients Terminated NCT03904420
34 Study of the Nucleus 24 and ABI541 Auditory Brainstem Implants in Pediatric Non-Neurofibromatosis Type 2 Terminated NCT01864291
35 Study of Nucleus 24 and ABI541 Auditory Brainstem Implants (ABI) in Adult Non-Neurofibromatosis Type 2 Subjects Terminated NCT01736267

Search NIH Clinical Center for Cardiospondylocarpofacial Syndrome

Cochrane evidence based reviews: hearing loss, bilateral

Genetic Tests for Cardiospondylocarpofacial Syndrome

Genetic tests related to Cardiospondylocarpofacial Syndrome:

# Genetic test Affiliating Genes
1 Cardiospondylocarpofacial Syndrome 29 MAP3K7

Anatomical Context for Cardiospondylocarpofacial Syndrome

MalaCards organs/tissues related to Cardiospondylocarpofacial Syndrome:

40
Heart, Bone, Kidney, Eye, Testis, Testes

Publications for Cardiospondylocarpofacial Syndrome

Articles related to Cardiospondylocarpofacial Syndrome:

# Title Authors PMID Year
1
Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome. 61 6 57
27426734 2016
2
Postnatal growth retardation, facial dysmorphism, spondylocarpal synostosis, cardiac defect, and inner ear malformation (cardiospondylocarpofacial syndrome?)--a distinct syndrome? 57 6 61
20186786 2010
3
Congenital heart disease, deafness, and skeletal malformations: a new syndrome? 57
5901343 1966
4
A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype. 61
32299812 2020
5
Insights into the molecular pathogenesis of cardiospondylocarpofacial syndrome: MAP3K7 c.737-7A > G variant alters the TGFβ-mediated α-SMA cytoskeleton assembly and autophagy. 61
32105826 2020
6
A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with features of hereditary connective tissue disorder. 61
29467388 2018

Variations for Cardiospondylocarpofacial Syndrome

ClinVar genetic disease variations for Cardiospondylocarpofacial Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MAP3K7 NM_145331.3(MAP3K7):c.130_135del (p.Arg44_Gly45del) Deletion Pathogenic 264702 rs886039234 GRCh37: 6:91281512-91281517
GRCh38: 6:90571793-90571798
2 MAP3K7 NM_145331.3(MAP3K7):c.721T>A (p.Trp241Arg) SNV Pathogenic 264705 rs886039237 GRCh37: 6:91263192-91263192
GRCh38: 6:90553473-90553473
3 MAP3K7 NM_145331.3(MAP3K7):c.328G>T (p.Gly110Cys) SNV Pathogenic 264703 rs886039235 GRCh37: 6:91271356-91271356
GRCh38: 6:90561637-90561637
4 MAP3K7 NM_145331.3(MAP3K7):c.145_147GTT[1] (p.Val50del) Microsatellite Pathogenic 264704 rs886039236 GRCh37: 6:91281497-91281499
GRCh38: 6:90571778-90571780
5 MAP3K7 NM_145331.3(MAP3K7):c.737-7A>G SNV Pathogenic 974910 GRCh37: 6:91261905-91261905
GRCh38: 6:90552186-90552186
6 MAP3K7 NM_145331.3(MAP3K7):c.143G>A (p.Gly48Glu) SNV Likely pathogenic 929459 GRCh37: 6:91281504-91281504
GRCh38: 6:90571785-90571785
7 MAP3K7 NM_145331.3(MAP3K7):c.122_124TTG[1] (p.Val42del) Microsatellite Likely pathogenic 684731 rs1582233787 GRCh37: 6:91281520-91281522
GRCh38: 6:90571801-90571803
8 MAP3K7 NM_145331.3(MAP3K7):c.248G>A (p.Arg83His) SNV Uncertain significance 689611 rs929527043 GRCh37: 6:91278326-91278326
GRCh38: 6:90568607-90568607
9 MAP3K7 NM_145331.3(MAP3K7):c.632A>G (p.Asp211Gly) SNV Uncertain significance 992915 GRCh37: 6:91263281-91263281
GRCh38: 6:90553562-90553562
10 MAP3K7 NM_145331.3(MAP3K7):c.868-17T>A SNV Uncertain significance 1031196 GRCh37: 6:91260285-91260285
GRCh38: 6:90550566-90550566

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

72
# Symbol AA change Variation ID SNP ID
1 MAP3K7 p.Gly110Cys VAR_077344 rs886039235
2 MAP3K7 p.Trp241Arg VAR_077346 rs886039237

Expression for Cardiospondylocarpofacial Syndrome

Search GEO for disease gene expression data for Cardiospondylocarpofacial Syndrome.

Pathways for Cardiospondylocarpofacial Syndrome

Pathways related to Cardiospondylocarpofacial Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.62 MAP3K7 FLNB
2
Show member pathways
11.27 MAP3K7 FLNB

GO Terms for Cardiospondylocarpofacial Syndrome

Sources for Cardiospondylocarpofacial Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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