MCID: ISL096
MIFTS: 34

Isolated Klippel-Feil Syndrome

Categories: Bone diseases, Fetal diseases, Rare diseases

Aliases & Classifications for Isolated Klippel-Feil Syndrome

MalaCards integrated aliases for Isolated Klippel-Feil Syndrome:

Name: Isolated Klippel-Feil Syndrome 58
Congenital Cervical Vertebral Fusion 58
Congenital Fused Cervical Segments 58
Klippel-Feil Malformation 58
Klippel-Feil Sequence 58

Characteristics:

Orphanet epidemiological data:

58
isolated klippel-feil syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: 1-9/100000 (Europe),1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Isolated Klippel-Feil Syndrome

MalaCards based summary : Isolated Klippel-Feil Syndrome, also known as congenital cervical vertebral fusion, is related to klippel-feil syndrome 1, autosomal dominant and klippel-feil syndrome. An important gene associated with Isolated Klippel-Feil Syndrome is GDF6 (Growth Differentiation Factor 6). Affiliated tissues include heart, and related phenotypes are short neck and webbed neck

Related Diseases for Isolated Klippel-Feil Syndrome

Graphical network of the top 20 diseases related to Isolated Klippel-Feil Syndrome:



Diseases related to Isolated Klippel-Feil Syndrome

Symptoms & Phenotypes for Isolated Klippel-Feil Syndrome

Human phenotypes related to Isolated Klippel-Feil Syndrome:

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000470
2 webbed neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000465
3 low posterior hairline 58 31 hallmark (90%) Very frequent (99-80%) HP:0002162
4 facial asymmetry 58 31 hallmark (90%) Very frequent (99-80%) HP:0000324
5 abnormal vertebral segmentation and fusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0005640
6 cervical c2/c3 vertebral fusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0004602
7 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
8 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
9 sprengel anomaly 58 31 frequent (33%) Frequent (79-30%) HP:0000912
10 abnormality of the ribs 58 31 frequent (33%) Frequent (79-30%) HP:0000772
11 congenital muscular torticollis 58 31 frequent (33%) Frequent (79-30%) HP:0005988
12 abnormal shoulder morphology 31 frequent (33%) HP:0003043
13 cognitive impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100543
14 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
15 renal hypoplasia/aplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008678
16 hemiplegia/hemiparesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0004374
17 anal atresia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002023
18 abnormal cranial nerve morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0001291
19 ventricular septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001629
20 spina bifida 58 31 occasional (7.5%) Occasional (29-5%) HP:0002414
21 abnormal sacrum morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0005107
22 ectopic anus 58 31 occasional (7.5%) Occasional (29-5%) HP:0004397
23 malformation of the heart and great vessels 58 Occasional (29-5%)
24 abnormality of the vertebral column 58 Very frequent (99-80%)
25 abnormality of the shoulder 58 Frequent (79-30%)

MGI Mouse Phenotypes related to Isolated Klippel-Feil Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.35 GDF3 GDF6 LRRK2 MEOX1 RIPPLY2
2 skeleton MP:0005390 8.92 GDF6 LRRK2 MEOX1 RIPPLY2

Drugs & Therapeutics for Isolated Klippel-Feil Syndrome

Search Clinical Trials , NIH Clinical Center for Isolated Klippel-Feil Syndrome

Genetic Tests for Isolated Klippel-Feil Syndrome

Anatomical Context for Isolated Klippel-Feil Syndrome

MalaCards organs/tissues related to Isolated Klippel-Feil Syndrome:

40
Heart

Publications for Isolated Klippel-Feil Syndrome

Articles related to Isolated Klippel-Feil Syndrome:

(show all 21)
# Title Authors PMID Year
1
Rare heterozygous GDF6 variants in patients with renal anomalies. 6
32737436 2020
2
Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome. 6
26238661 2015
3
Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects. 6
25343988 2015
4
Mutation in MEOX1 gene causes a recessive Klippel-Feil syndrome subtype. 6
24073994 2013
5
Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. 6
23307924 2013
6
Mutations in MEOX1, encoding mesenchyme homeobox 1, cause Klippel-Feil anomaly. 6
23290072 2013
7
Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. 6
19864492 2010
8
Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. 6
19129173 2009
9
Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. 6
18425797 2008
10
Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease. 6
18412265 2008
11
LRRK2 Parkinson Disease 6
20301387 2006
12
Heterozygous loss of WBP11 function causes multiple congenital defects in humans and mice. 61
33276377 2020
13
Central sleep apnea and Chiari 1 malformation in a pediatric patient with Klippel-Feil syndrome. 61
32620190 2020
14
Klippel - Feil Syndrome Associated with Congential Heart Disease Presentaion of Cases and a Review of the Curent Literature. 61
27275209 2015
15
Developmental anomalies of the scapula-the "omo"st forgotten bone. 61
12884444 2003
16
Is there a relation between Klippel-Feil sequence and Kallmann syndrome? 61
7762597 1995
17
Cholelithiasis in cervico-oculo-acoustic (Wildervanck's) syndrome. 61
8241656 1993
18
Klippel-Feil sequence and sleep-disordered breathing in two children. 61
8420417 1993
19
Cervical neurenteric fistula causing recurrent meningitis in Klippel-Feil sequence: case report and literature review. 61
1876469 1991
20
Cervico-oculo-acusticus (Wildervanck's) syndrome: a clinical variant of Klippel-Feil sequence? 61
2355722 1990
21
Association of the Klippel-Feil sequence with frontonasal dysplasia sequence. 61
6641005 1983

Variations for Isolated Klippel-Feil Syndrome

ClinVar genetic disease variations for Isolated Klippel-Feil Syndrome:

6 (show top 50) (show all 149)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GDF6 NM_001001557.4(GDF6):c.1271A>G (p.Lys424Arg) SNV Pathogenic 8373 rs121909353 GRCh37: 8:97156888-97156888
GRCh38: 8:96144660-96144660
2 GDF6 NM_001001557.4(GDF6):c.125G>T (p.Gly42Val) SNV Pathogenic 8374 rs121909354 GRCh37: 8:97172796-97172796
GRCh38: 8:96160568-96160568
3 GDF6 NM_001001557.4(GDF6):c.1271A>G (p.Lys424Arg) SNV Pathogenic 8373 rs121909353 GRCh37: 8:97156888-97156888
GRCh38: 8:96144660-96144660
4 LRRK2 NM_198578.4(LRRK2):c.4883G>C (p.Arg1628Pro) SNV Pathogenic 39198 rs33949390 GRCh37: 12:40713845-40713845
GRCh38: 12:40320043-40320043
5 GDF6 NM_001001557.4(GDF6):c.866T>C (p.Leu289Pro) SNV Pathogenic 8372 rs63751220 GRCh37: 8:97157293-97157293
GRCh38: 8:96145065-96145065
6 GDF6 NM_001001557.4(GDF6):c.746C>A (p.Ala249Glu) SNV Pathogenic 8371 rs121909352 GRCh37: 8:97157413-97157413
GRCh38: 8:96145185-96145185
7 MEOX1 NM_004527.4(MEOX1):c.94del (p.Ala32fs) Deletion Pathogenic 39507 rs1567750527 GRCh37: 17:41738809-41738809
GRCh38: 17:43661441-43661441
8 MEOX1 NM_004527.4(MEOX1):c.664C>T (p.Arg222Ter) SNV Pathogenic 39508 rs772798486 GRCh37: 17:41719379-41719379
GRCh38: 17:43642011-43642011
9 MEOX1 NM_004527.4(MEOX1):c.250C>T (p.Gln84Ter) SNV Pathogenic 162132 rs713993044 GRCh37: 17:41738653-41738653
GRCh38: 17:43661285-43661285
10 MEOX1 NM_004527.4(MEOX1):c.125del (p.Pro42fs) Deletion Pathogenic 1029858 GRCh37: 17:41738778-41738778
GRCh38: 17:43661410-43661410
11 GDF6 NM_001001557.4(GDF6):c.169G>C (p.Asp57His) SNV Likely pathogenic 60534 rs397514725 GRCh37: 8:97172752-97172752
GRCh38: 8:96160524-96160524
12 GDF3 NM_020634.3(GDF3):c.796C>T (p.Arg266Cys) SNV Likely pathogenic 30591 rs140926412 GRCh37: 12:7842773-7842773
GRCh38: 12:7690177-7690177
13 RIPPLY2 NM_001009994.2(RIPPLY2):c.299del (p.Leu100fs) Deletion Likely pathogenic 218314 rs864309489 GRCh37: 6:84567020-84567020
GRCh38: 6:83857301-83857301
14 GDF6 NM_001001557.4(GDF6):c.742C>A (p.Arg248Ser) SNV Uncertain significance 364048 rs750809706 GRCh37: 8:97157417-97157417
GRCh38: 8:96145189-96145189
15 GDF6 NM_001001557.4(GDF6):c.*276T>C SNV Uncertain significance 364031 rs886063204 GRCh37: 8:97156515-97156515
GRCh38: 8:96144287-96144287
16 GDF6 NM_001001557.4(GDF6):c.*58G>A SNV Uncertain significance 364040 rs886063207 GRCh37: 8:97156733-97156733
GRCh38: 8:96144505-96144505
17 GDF6 NM_001001557.4(GDF6):c.*2214C>T SNV Uncertain significance 364006 rs188995955 GRCh37: 8:97154577-97154577
GRCh38: 8:96142349-96142349
18 GDF6 NM_001001557.4(GDF6):c.741G>A (p.Ala247=) SNV Uncertain significance 364049 rs563560538 GRCh37: 8:97157418-97157418
GRCh38: 8:96145190-96145190
19 GDF6 NM_001001557.4(GDF6):c.*280T>C SNV Uncertain significance 364029 rs886063202 GRCh37: 8:97156511-97156511
GRCh38: 8:96144283-96144283
20 GDF6 NM_001001557.4(GDF6):c.*268G>C SNV Uncertain significance 364035 rs575001243 GRCh37: 8:97156523-97156523
GRCh38: 8:96144295-96144295
21 GDF6 NM_001001557.4(GDF6):c.*653C>A SNV Uncertain significance 364021 rs886063196 GRCh37: 8:97156138-97156138
GRCh38: 8:96143910-96143910
22 GDF6 NM_001001557.4(GDF6):c.499C>T (p.Arg167Trp) SNV Uncertain significance 364050 rs886063209 GRCh37: 8:97157660-97157660
GRCh38: 8:96145432-96145432
23 GDF6 NM_001001557.4(GDF6):c.*249G>A SNV Uncertain significance 364036 rs886063206 GRCh37: 8:97156542-97156542
GRCh38: 8:96144314-96144314
24 GDF6 NM_001001557.4(GDF6):c.*891G>A SNV Uncertain significance 364016 rs376103537 GRCh37: 8:97155900-97155900
GRCh38: 8:96143672-96143672
25 GDF6 NM_001001557.4(GDF6):c.*288T>A SNV Uncertain significance 364028 rs886063201 GRCh37: 8:97156503-97156503
GRCh38: 8:96144275-96144275
26 GDF6 NM_001001557.4(GDF6):c.815C>T (p.Pro272Leu) SNV Uncertain significance 836995 GRCh37: 8:97157344-97157344
GRCh38: 8:96145116-96145116
27 GDF6 NM_001001557.4(GDF6):c.*2215G>A SNV Uncertain significance 912481 GRCh37: 8:97154576-97154576
GRCh38: 8:96142348-96142348
28 GDF6 NM_001001557.4(GDF6):c.*725C>A SNV Uncertain significance 912527 GRCh37: 8:97156066-97156066
GRCh38: 8:96143838-96143838
29 GDF6 NM_001001557.4(GDF6):c.*647C>T SNV Uncertain significance 912528 GRCh37: 8:97156144-97156144
GRCh38: 8:96143916-96143916
30 GDF6 NM_001001557.4(GDF6):c.*620A>G SNV Uncertain significance 912529 GRCh37: 8:97156171-97156171
GRCh38: 8:96143943-96143943
31 GDF6 NM_001001557.4(GDF6):c.*546G>C SNV Uncertain significance 912530 GRCh37: 8:97156245-97156245
GRCh38: 8:96144017-96144017
32 GDF6 NM_001001557.4(GDF6):c.*529C>G SNV Uncertain significance 912531 GRCh37: 8:97156262-97156262
GRCh38: 8:96144034-96144034
33 GDF6 NM_001001557.4(GDF6):c.*1781G>C SNV Uncertain significance 913597 GRCh37: 8:97155010-97155010
GRCh38: 8:96142782-96142782
34 GDF6 NM_001001557.4(GDF6):c.*405G>A SNV Uncertain significance 913637 GRCh37: 8:97156386-97156386
GRCh38: 8:96144158-96144158
35 GDF6 NM_001001557.4(GDF6):c.*333G>T SNV Uncertain significance 913638 GRCh37: 8:97156458-97156458
GRCh38: 8:96144230-96144230
36 GDF6 NM_001001557.4(GDF6):c.*319A>C SNV Uncertain significance 913639 GRCh37: 8:97156472-97156472
GRCh38: 8:96144244-96144244
37 GDF6 NM_001001557.4(GDF6):c.743G>T (p.Arg248Leu) SNV Uncertain significance 913678 GRCh37: 8:97157416-97157416
GRCh38: 8:96145188-96145188
38 GDF6 NM_001001557.4(GDF6):c.716A>G (p.Glu239Gly) SNV Uncertain significance 913679 GRCh37: 8:97157443-97157443
GRCh38: 8:96145215-96145215
39 GDF6 NM_001001557.4(GDF6):c.701G>A (p.Arg234Gln) SNV Uncertain significance 913680 GRCh37: 8:97157458-97157458
GRCh38: 8:96145230-96145230
40 GDF6 NM_001001557.4(GDF6):c.957C>A (p.Ala319=) SNV Uncertain significance 364044 rs757525366 GRCh37: 8:97157202-97157202
GRCh38: 8:96144974-96144974
41 GDF3 NM_020634.3(GDF3):c.709A>G (p.Thr237Ala) SNV Uncertain significance 538877 rs934067367 GRCh37: 12:7842860-7842860
GRCh38: 12:7690264-7690264
42 GDF3 NM_020634.3(GDF3):c.161T>C (p.Ile54Thr) SNV Uncertain significance 642837 rs910081119 GRCh37: 12:7848164-7848164
GRCh38: 12:7695568-7695568
43 GDF6 NM_001001557.4(GDF6):c.770C>T (p.Pro257Leu) SNV Uncertain significance 364047 rs886063208 GRCh37: 8:97157389-97157389
GRCh38: 8:96145161-96145161
44 GDF6 NM_001001557.4(GDF6):c.1310A>G (p.Asn437Ser) SNV Uncertain significance 1001816 GRCh37: 8:97156849-97156849
GRCh38: 8:96144621-96144621
45 GDF6 NM_001001557.4(GDF6):c.536C>A (p.Pro179Gln) SNV Uncertain significance 1002016 GRCh37: 8:97157623-97157623
GRCh38: 8:96145395-96145395
46 GDF6 NM_001001557.4(GDF6):c.896C>T (p.Ser299Leu) SNV Uncertain significance 1002101 GRCh37: 8:97157263-97157263
GRCh38: 8:96145035-96145035
47 GDF6 NM_001001557.4(GDF6):c.611C>T (p.Pro204Leu) SNV Uncertain significance 1007576 GRCh37: 8:97157548-97157548
GRCh38: 8:96145320-96145320
48 GDF6 NM_001001557.4(GDF6):c.377C>T (p.Thr126Met) SNV Uncertain significance 1008100 GRCh37: 8:97172544-97172544
GRCh38: 8:96160316-96160316
49 GDF6 NM_001001557.4(GDF6):c.272G>C (p.Arg91Pro) SNV Uncertain significance 1008463 GRCh37: 8:97172649-97172649
GRCh38: 8:96160421-96160421
50 GDF6 NM_001001557.4(GDF6):c.281C>G (p.Pro94Arg) SNV Uncertain significance 1009700 GRCh37: 8:97172640-97172640
GRCh38: 8:96160412-96160412

Expression for Isolated Klippel-Feil Syndrome

Search GEO for disease gene expression data for Isolated Klippel-Feil Syndrome.

Pathways for Isolated Klippel-Feil Syndrome

GO Terms for Isolated Klippel-Feil Syndrome

Biological processes related to Isolated Klippel-Feil Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 BMP signaling pathway GO:0030509 9.26 GDF6 GDF3
2 SMAD protein signal transduction GO:0060395 9.16 GDF6 GDF3
3 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 8.96 GDF6 GDF3
4 multicellular organism development GO:0007275 8.92 RIPPLY2 MEOX1 GDF6 GDF3

Molecular functions related to Isolated Klippel-Feil Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine activity GO:0005125 8.96 GDF6 GDF3
2 growth factor activity GO:0008083 8.62 GDF6 GDF3

Sources for Isolated Klippel-Feil 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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