KFS1
MCID: KLP007
MIFTS: 34

Klippel-Feil Syndrome 1, Autosomal Dominant (KFS1)

Categories: Bone diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Klippel-Feil Syndrome 1, Autosomal Dominant

MalaCards integrated aliases for Klippel-Feil Syndrome 1, Autosomal Dominant:

Name: Klippel-Feil Syndrome 1, Autosomal Dominant 57 72 29 13 6
Cervical Vertebral Fusion Autosomal Dominant 72 6
Kfs1 57 72
Syndrome, Klippel-Feil, Type 1, Autosomal Dominant 39
Cervical Vertebral Fusion, Autosomal Dominant 57
Klippel-Feil Syndrome, Autosomal Dominant 70
Cervical Vertebral Fusion Congenital 72
Fused Cervical Segments Congenital 72
Congenital Klippel-Feil Segment 72
Isolated Klippel-Feil Syndrome 72
Klippel-Feil Malformation 72
Klippel-Feil Sequence 72
Kfs 57

Characteristics:

OMIM®:

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

Miscellaneous:
variable severity
genetic heterogeneity (see )
klippel-feil anomaly may be a part of other syndromes, including murcs and sprengel deformity


HPO:

31
klippel-feil syndrome 1, autosomal dominant:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course variable expressivity


Classifications:



External Ids:

OMIM® 57 118100
OMIM Phenotypic Series 57 PS118100
MeSH 44 D007714
MedGen 41 C1861689
UMLS 70 C1861689

Summaries for Klippel-Feil Syndrome 1, Autosomal Dominant

UniProtKB/Swiss-Prot : 72 Klippel-Feil syndrome 1, autosomal dominant: A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. Deafness is a feature in some cases and may be of sensorineural, conductive, or mixed type.

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

OMIM® : 57 Klippel-Feil syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in a fused appearance. The clinical triad consists of short neck, low posterior hairline, and limited neck movement, although less than 50% of patients demonstrate all 3 clinical features (Tracy et al., 2004). (118100) (Updated 05-Apr-2021)

Related Diseases for Klippel-Feil Syndrome 1, Autosomal Dominant

Graphical network of the top 20 diseases related to Klippel-Feil Syndrome 1, Autosomal Dominant:



Diseases related to Klippel-Feil Syndrome 1, Autosomal Dominant

Symptoms & Phenotypes for Klippel-Feil Syndrome 1, Autosomal Dominant

Human phenotypes related to Klippel-Feil Syndrome 1, Autosomal Dominant:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 short neck 31 hallmark (90%) HP:0000470
2 abnormal vertebral segmentation and fusion 31 hallmark (90%) HP:0005640
3 cervical c2/c3 vertebral fusion 31 hallmark (90%) HP:0004602
4 limited neck range of motion 31 hallmark (90%) HP:0000466
5 low posterior hairline 31 frequent (33%) HP:0002162
6 cleft palate 31 occasional (7.5%) HP:0000175
7 abnormality of the ribs 31 occasional (7.5%) HP:0000772
8 abnormality of limb bone morphology 31 occasional (7.5%) HP:0002813
9 posterior fossa cyst 31 occasional (7.5%) HP:0007291
10 scoliosis 31 very rare (1%) HP:0002650
11 webbed neck 31 very rare (1%) HP:0000465
12 sprengel anomaly 31 very rare (1%) HP:0000912
13 facial asymmetry 31 very rare (1%) HP:0000324
14 congenital muscular torticollis 31 very rare (1%) HP:0005988
15 unilateral renal agenesis 31 very rare (1%) HP:0000122
16 abnormality of cardiovascular system morphology 31 very rare (1%) HP:0030680
17 mixed hearing impairment 31 very rare (1%) HP:0000410
18 bimanual synkinesia 31 very rare (1%) HP:0001335
19 cervicomedullary schisis 31 HP:0030325

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Spine:
scoliosis
fusion of cervical vertebrae, most often c2-3

Head And Neck Mouth:
cleft palate

Chest Ribs Sternum Clavicles And Scapulae:
sprengel anomaly

Head And Neck Ears:
hearing loss, conductive
hearing loss, sensorineural

Head And Neck Neck:
short neck
limited neck range of motion

Skin Nails Hair Hair:
low posterior hairline

Head And Neck Face:
facial asymmetry

Clinical features from OMIM®:

118100 (Updated 05-Apr-2021)

Drugs & Therapeutics for Klippel-Feil Syndrome 1, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Klippel-Feil Syndrome 1, Autosomal Dominant

Genetic Tests for Klippel-Feil Syndrome 1, Autosomal Dominant

Genetic tests related to Klippel-Feil Syndrome 1, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Klippel-Feil Syndrome 1, Autosomal Dominant 29 GDF6

Anatomical Context for Klippel-Feil Syndrome 1, Autosomal Dominant

MalaCards organs/tissues related to Klippel-Feil Syndrome 1, Autosomal Dominant:

40
Bone, Heart

Publications for Klippel-Feil Syndrome 1, Autosomal Dominant

Articles related to Klippel-Feil Syndrome 1, Autosomal Dominant:

(show all 29)
# Title Authors PMID Year
1
Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. 57 6
19129173 2009
2
Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. 6 57
18425797 2008
3
Rare heterozygous GDF6 variants in patients with renal anomalies. 6
32737436 2020
4
Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. 6
23307924 2013
5
Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease. 6
18412265 2008
6
LRRK2 Parkinson Disease 6
20301387 2006
7
Familial Klippel-Feil anomaly and t(5;8)(q35.1;p21.1) translocation. 57
16575895 2006
8
Monozygotic twins discordant for Klippel-Feil syndrome. 57
16376286 2006
9
Neural crest origins of the neck and shoulder. 57
16034409 2005
10
Klippel-Feil syndrome: clinical features and current understanding of etiology. 57
15241163 2004
11
Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. 57
12606286 2003
12
Heterogeneity in Klippel-Feil syndrome: a new classification. 57
9880643 1998
13
Audiological abnormalities in the Klippel-Feil syndrome. 57
9875048 1998
14
Autosomal dominant Klippel-Feil anomaly with cleft palate. 57
9546824 1998
15
Familial Klippel-Feil syndrome and paracentric inversion inv(8)(q22.2q23.3). 57
8533765 1995
16
Klippel-Feil syndrome associated with malformed larynx. Case report. 57
8122836 1994
17
Klippel-Feil anomaly with sacral agenesis: an additional subtype, type IV. 57
3065353 1988
18
Subclavian artery supply disruption sequence: hypothesis of a vascular etiology for Poland, Klippel-Feil, and Möbius anomalies. 57
3008556 1986
19
The Klippel-Feil syndrome: genetic and clinical reevaluation of cervical fusion. 57
4867516 1967
20
An analysis of the Klippel-Feil syndrome. 57
21019989 1946
21
Central sleep apnea and Chiari 1 malformation in a pediatric patient with Klippel-Feil syndrome. 61
32620190 2020
22
Klippel - Feil Syndrome Associated with Congential Heart Disease Presentaion of Cases and a Review of the Curent Literature. 61
27275209 2015
23
Developmental anomalies of the scapula-the "omo"st forgotten bone. 61
12884444 2003
24
Is there a relation between Klippel-Feil sequence and Kallmann syndrome? 61
7762597 1995
25
Cholelithiasis in cervico-oculo-acoustic (Wildervanck's) syndrome. 61
8241656 1993
26
Klippel-Feil sequence and sleep-disordered breathing in two children. 61
8420417 1993
27
Cervical neurenteric fistula causing recurrent meningitis in Klippel-Feil sequence: case report and literature review. 61
1876469 1991
28
Cervico-oculo-acusticus (Wildervanck's) syndrome: a clinical variant of Klippel-Feil sequence? 61
2355722 1990
29
Association of the Klippel-Feil sequence with frontonasal dysplasia sequence. 61
6641005 1983

Variations for Klippel-Feil Syndrome 1, Autosomal Dominant

ClinVar genetic disease variations for Klippel-Feil Syndrome 1, Autosomal Dominant:

6 (show top 50) (show all 137)
# 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.746C>A (p.Ala249Glu) SNV Pathogenic 8371 rs121909352 GRCh37: 8:97157413-97157413
GRCh38: 8:96145185-96145185
6 GDF6 NM_001001557.4(GDF6):c.866T>C (p.Leu289Pro) SNV Pathogenic 8372 rs63751220 GRCh37: 8:97157293-97157293
GRCh38: 8:96145065-96145065
7 MYO18B NM_032608.7(MYO18B):c.5038dup (p.Glu1680fs) Duplication Likely pathogenic 634522 rs1569172839 GRCh37: 22:26299683-26299684
GRCh38: 22:25903716-25903717
8 GDF6 NM_001001557.4(GDF6):c.169G>C (p.Asp57His) SNV Likely pathogenic 60534 rs397514725 GRCh37: 8:97172752-97172752
GRCh38: 8:96160524-96160524
9 GDF6 NM_001001557.4(GDF6):c.631G>A (p.Gly211Ser) SNV Uncertain significance 1034940 GRCh37: 8:97157528-97157528
GRCh38: 8:96145300-96145300
10 GDF6 NM_001001557.4(GDF6):c.883G>A (p.Glu295Lys) SNV Uncertain significance 1037153 GRCh37: 8:97157276-97157276
GRCh38: 8:96145048-96145048
11 GDF6 NM_001001557.4(GDF6):c.1322A>G (p.Tyr441Cys) SNV Uncertain significance 1043780 GRCh37: 8:97156837-97156837
GRCh38: 8:96144609-96144609
12 GDF6 NM_001001557.4(GDF6):c.1304C>T (p.Ala435Val) SNV Uncertain significance 364042 rs140782427 GRCh37: 8:97156855-97156855
GRCh38: 8:96144627-96144627
13 GDF6 NM_001001557.4(GDF6):c.460A>G (p.Met154Val) SNV Uncertain significance 835633 GRCh37: 8:97157699-97157699
GRCh38: 8:96145471-96145471
14 GDF6 NM_001001557.4(GDF6):c.623C>T (p.Pro208Leu) SNV Uncertain significance 837877 GRCh37: 8:97157536-97157536
GRCh38: 8:96145308-96145308
15 GDF6 NM_001001557.4(GDF6):c.27G>A (p.Ser9=) SNV Uncertain significance 846167 GRCh37: 8:97172894-97172894
GRCh38: 8:96160666-96160666
16 GDF6 NM_001001557.4(GDF6):c.428T>C (p.Leu143Pro) SNV Uncertain significance 853665 GRCh37: 8:97157731-97157731
GRCh38: 8:96145503-96145503
17 GDF6 NM_001001557.4(GDF6):c.322G>A (p.Ala108Thr) SNV Uncertain significance 863448 GRCh37: 8:97172599-97172599
GRCh38: 8:96160371-96160371
18 GDF6 NM_001001557.4(GDF6):c.*908G>A SNV Uncertain significance 915224 GRCh37: 8:97155883-97155883
GRCh38: 8:96143655-96143655
19 GDF6 NM_001001557.4(GDF6):c.*868C>T SNV Uncertain significance 915225 GRCh37: 8:97155923-97155923
GRCh38: 8:96143695-96143695
20 GDF6 NM_001001557.4(GDF6):c.*734T>C SNV Uncertain significance 915226 GRCh37: 8:97156057-97156057
GRCh38: 8:96143829-96143829
21 GDF6 NM_001001557.4(GDF6):c.878T>C (p.Met293Thr) SNV Uncertain significance 959329 GRCh37: 8:97157281-97157281
GRCh38: 8:96145053-96145053
22 GDF6 NM_001001557.4(GDF6):c.725C>G (p.Ala242Gly) SNV Uncertain significance 286405 rs886043381 GRCh37: 8:97157434-97157434
GRCh38: 8:96145206-96145206
23 GDF6 NM_001001557.4(GDF6):c.362C>T (p.Ser121Phe) SNV Uncertain significance 968855 GRCh37: 8:97172559-97172559
GRCh38: 8:96160331-96160331
24 GDF6 NM_001001557.4(GDF6):c.746C>A (p.Ala249Glu) SNV Uncertain significance 8371 rs121909352 GRCh37: 8:97157413-97157413
GRCh38: 8:96145185-96145185
25 GDF6 NM_001001557.4(GDF6):c.957C>A (p.Ala319=) SNV Uncertain significance 364044 rs757525366 GRCh37: 8:97157202-97157202
GRCh38: 8:96144974-96144974
26 GDF6 NM_001001557.4(GDF6):c.*2189T>C SNV Uncertain significance 913595 GRCh37: 8:97154602-97154602
GRCh38: 8:96142374-96142374
27 GDF6 NM_001001557.4(GDF6):c.24C>G (p.Leu8=) SNV Uncertain significance 707560 rs369859861 GRCh37: 8:97172897-97172897
GRCh38: 8:96160669-96160669
28 GDF6 NM_001001557.4(GDF6):c.18C>T (p.Val6=) SNV Uncertain significance 914078 GRCh37: 8:97172903-97172903
GRCh38: 8:96160675-96160675
29 GDF6 NM_001001557.4(GDF6):c.-86C>T SNV Uncertain significance 914079 GRCh37: 8:97173006-97173006
GRCh38: 8:96160778-96160778
30 GDF6 NM_001001557.4(GDF6):c.*106A>T SNV Uncertain significance 914547 GRCh37: 8:97156685-97156685
GRCh38: 8:96144457-96144457
31 GDF6 NM_001001557.4(GDF6):c.*27G>A SNV Uncertain significance 914548 GRCh37: 8:97156764-97156764
GRCh38: 8:96144536-96144536
32 GDF6 NM_001001557.4(GDF6):c.1348G>A (p.Glu450Lys) SNV Uncertain significance 914549 GRCh37: 8:97156811-97156811
GRCh38: 8:96144583-96144583
33 GDF6 NM_001001557.4(GDF6):c.305A>G (p.Tyr102Cys) SNV Uncertain significance 954499 GRCh37: 8:97172616-97172616
GRCh38: 8:96160388-96160388
34 GDF6 NM_001001557.4(GDF6):c.250G>A (p.Glu84Lys) SNV Uncertain significance 914077 GRCh37: 8:97172671-97172671
GRCh38: 8:96160443-96160443
35 GDF6 NM_001001557.4(GDF6):c.253C>T (p.Pro85Ser) SNV Uncertain significance 958860 GRCh37: 8:97172668-97172668
GRCh38: 8:96160440-96160440
36 GDF6 NM_001001557.4(GDF6):c.758A>G (p.Gln253Arg) SNV Uncertain significance 964319 GRCh37: 8:97157401-97157401
GRCh38: 8:96145173-96145173
37 GDF6 NM_001001557.4(GDF6):c.770C>T (p.Pro257Leu) SNV Uncertain significance 364047 rs886063208 GRCh37: 8:97157389-97157389
GRCh38: 8:96145161-96145161
38 GDF6 NM_001001557.4(GDF6):c.1310A>G (p.Asn437Ser) SNV Uncertain significance 1001816 GRCh37: 8:97156849-97156849
GRCh38: 8:96144621-96144621
39 GDF6 NM_001001557.4(GDF6):c.536C>A (p.Pro179Gln) SNV Uncertain significance 1002016 GRCh37: 8:97157623-97157623
GRCh38: 8:96145395-96145395
40 GDF6 NM_001001557.4(GDF6):c.896C>T (p.Ser299Leu) SNV Uncertain significance 1002101 GRCh37: 8:97157263-97157263
GRCh38: 8:96145035-96145035
41 GDF6 NM_001001557.4(GDF6):c.611C>T (p.Pro204Leu) SNV Uncertain significance 1007576 GRCh37: 8:97157548-97157548
GRCh38: 8:96145320-96145320
42 GDF6 NM_001001557.4(GDF6):c.377C>T (p.Thr126Met) SNV Uncertain significance 1008100 GRCh37: 8:97172544-97172544
GRCh38: 8:96160316-96160316
43 GDF6 NM_001001557.4(GDF6):c.272G>C (p.Arg91Pro) SNV Uncertain significance 1008463 GRCh37: 8:97172649-97172649
GRCh38: 8:96160421-96160421
44 GDF6 NM_001001557.4(GDF6):c.281C>G (p.Pro94Arg) SNV Uncertain significance 1009700 GRCh37: 8:97172640-97172640
GRCh38: 8:96160412-96160412
45 GDF6 NM_001001557.4(GDF6):c.167G>C (p.Arg56Pro) SNV Uncertain significance 836171 GRCh37: 8:97172754-97172754
GRCh38: 8:96160526-96160526
46 GDF6 NM_001001557.4(GDF6):c.785G>A (p.Ser262Asn) SNV Uncertain significance 939495 GRCh37: 8:97157374-97157374
GRCh38: 8:96145146-96145146
47 GDF6 NM_001001557.4(GDF6):c.856C>T (p.Arg286Cys) SNV Uncertain significance 954246 GRCh37: 8:97157303-97157303
GRCh38: 8:96145075-96145075
48 GDF6 NM_001001557.4(GDF6):c.223C>A (p.Pro75Thr) SNV Uncertain significance 962453 GRCh37: 8:97172698-97172698
GRCh38: 8:96160470-96160470
49 GDF6 NM_001001557.4(GDF6):c.82A>C (p.Ile28Leu) SNV Uncertain significance 965244 GRCh37: 8:97172839-97172839
GRCh38: 8:96160611-96160611
50 GDF6 NM_001001557.4(GDF6):c.996GCG[4] (p.Arg335dup) Microsatellite Uncertain significance 968900 GRCh37: 8:97157154-97157155
GRCh38: 8:96144926-96144927

UniProtKB/Swiss-Prot genetic disease variations for Klippel-Feil Syndrome 1, Autosomal Dominant:

72
# Symbol AA change Variation ID SNP ID
1 GDF6 p.Ala249Glu VAR_046903 rs121909352
2 GDF6 p.Leu289Pro VAR_046904 rs63751220
3 GDF6 p.Gly42Val VAR_063024 rs121909354
4 GDF6 p.Lys424Arg VAR_063029 rs121909353

Expression for Klippel-Feil Syndrome 1, Autosomal Dominant

Search GEO for disease gene expression data for Klippel-Feil Syndrome 1, Autosomal Dominant.

Pathways for Klippel-Feil Syndrome 1, Autosomal Dominant

GO Terms for Klippel-Feil Syndrome 1, Autosomal Dominant

Molecular functions related to Klippel-Feil Syndrome 1, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actin binding GO:0003779 8.62 MYO18B LRRK2

Sources for Klippel-Feil Syndrome 1, Autosomal Dominant

3 CDC
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