KTLS
MCID: KTL001
MIFTS: 39

Keutel Syndrome (KTLS)

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

Aliases & Classifications for Keutel Syndrome

MalaCards integrated aliases for Keutel Syndrome:

Name: Keutel Syndrome 58 77 54 60 76 38 30 13 56 6 41 74
Ktls 58 76
Pulmonic Stenosis-Brachytelephalangism-Calcification of Cartilages Syndrome 60
Pulmonic Stenosis, Brachytelephalangism, and Calcification of Cartilages 58
Pulmonic Stenosis Brachytelephalangism and Calcification of Cartilages 54

Characteristics:

Orphanet epidemiological data:

60
keutel syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
keutel syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Keutel Syndrome

NIH Rare Diseases : 54 Keutel syndrome is an inherited condition characterized by cartilage calcification in the ears, nose, larnyx, trachea (voice box), and ribs; pulmonary artery stenoses; brachytelephalangism (short fingers and nails that resemble drumsticks); and facial dysmorphism. Less than 30 cases have been reported in the literature. The majority of affected individuals have been diagnosed during childhood. Other associated features may include hearing loss, recurrent otitis and/or sinusitis, mild intellectual disability, frequent respiratory infections, nasal speech and rarely, seizures, and short stature. This condition is inherited in an autosomal recessive fashion and is caused by mutations in the MGP gene.

MalaCards based summary : Keutel Syndrome, also known as ktls, is related to nasodigitoacoustic syndrome and breast cancer, and has symptoms including seizures An important gene associated with Keutel Syndrome is MGP (Matrix Gla Protein). Affiliated tissues include trachea, bone and skin, and related phenotypes are depressed nasal bridge and long face

OMIM : 58 Keutel syndrome is an autosomal recessive disorder characterized by multiple peripheral pulmonary stenoses, brachytelephalangy, inner ear deafness, and abnormal cartilage ossification or calcification (summary by Khosroshahi et al., 2014). (245150)

UniProtKB/Swiss-Prot : 76 Keutel syndrome: An autosomal recessive disorder characterized by abnormal cartilage calcification, peripheral pulmonary stenosis neural hearing loss and midfacial hypoplasia.

Wikipedia : 77 Keutel syndrome (KS) is a rare autosomal recessive genetic disorder characterized by abnormal diffuse... more...

Related Diseases for Keutel Syndrome

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

# Related Disease Score Top Affiliating Genes
1 nasodigitoacoustic syndrome 11.1
2 breast cancer 10.2
3 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
4 relapsing polychondritis 10.0
5 cutis laxa 10.0
6 peripheral pulmonary stenosis 10.0
7 osteoporosis 9.7 BMP2 MGP
8 kidney disease 9.4 GLA MGP

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



Diseases related to Keutel Syndrome

Symptoms & Phenotypes for Keutel Syndrome

Human phenotypes related to Keutel Syndrome:

60 33 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressed nasal bridge 60 33 hallmark (90%) Very frequent (99-80%) HP:0005280
2 long face 60 33 hallmark (90%) Very frequent (99-80%) HP:0000276
3 midface retrusion 60 33 hallmark (90%) Very frequent (99-80%) HP:0011800
4 short distal phalanx of finger 60 33 hallmark (90%) Very frequent (99-80%) HP:0009882
5 pulmonary artery stenosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0004415
6 wide nose 60 33 hallmark (90%) Very frequent (99-80%) HP:0000445
7 calcification of cartilage 60 33 hallmark (90%) Very frequent (99-80%) HP:0100593
8 tracheal atresia 60 33 hallmark (90%) Very frequent (99-80%) HP:0100682
9 hearing impairment 60 33 frequent (33%) Frequent (79-30%) HP:0000365
10 global developmental delay 60 33 frequent (33%) Frequent (79-30%) HP:0001263
11 intellectual disability, mild 60 33 frequent (33%) Frequent (79-30%) HP:0001256
12 pulmonary arterial hypertension 60 33 frequent (33%) Frequent (79-30%) HP:0002092
13 recurrent otitis media 60 33 frequent (33%) Frequent (79-30%) HP:0000403
14 underdeveloped nasal alae 60 33 frequent (33%) Frequent (79-30%) HP:0000430
15 ventricular septal defect 60 33 frequent (33%) Frequent (79-30%) HP:0001629
16 sloping forehead 60 33 frequent (33%) Frequent (79-30%) HP:0000340
17 recurrent sinusitis 60 33 frequent (33%) Frequent (79-30%) HP:0011108
18 seizures 60 33 occasional (7.5%) Occasional (29-5%) HP:0001250
19 optic atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0000648
20 short stature 60 33 occasional (7.5%) Occasional (29-5%) HP:0004322
21 alopecia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001596
22 dermal atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0004334
23 soft, doughy skin 60 33 occasional (7.5%) Occasional (29-5%) HP:0001027
24 malar flattening 33 HP:0000272
25 hypertension 33 HP:0000822
26 cerebral calcification 33 HP:0002514
27 macrotia 33 HP:0000400
28 recurrent respiratory infections 60 Frequent (79-30%)
29 emphysema 33 HP:0002097
30 sinusitis 33 HP:0000246
31 epiphyseal stippling 33 HP:0010655
32 nasal speech 33 HP:0001611
33 deep philtrum 33 HP:0002002
34 pulmonic stenosis 33 HP:0001642
35 peripheral pulmonary artery stenosis 33 HP:0004969
36 short hallux 33 HP:0010109
37 spontaneous abortion 33 HP:0005268
38 chronic sinusitis 33 HP:0011109
39 short thumb 33 HP:0009778
40 pulmonary artery hypoplasia 33 HP:0004971
41 obstructive lung disease 33 HP:0006536
42 calcification of the auricular cartilage 33 HP:0005103
43 recurrent bronchitis 33 HP:0002837
44 costal cartilage calcification 33 HP:0006646
45 cartilaginous ossification of nose 33 HP:0005275
46 cartilaginous ossification of larynx 33 HP:0008747
47 premature fusion of phalangeal epiphyses 33 HP:0006140
48 growth abnormality 33 HP:0001507

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
normal intelligence
mental retardation, mild
cerebral calcifications

Head And Neck Face:
long face
deep philtrum
midface hypoplasia, mild

Cardiovascular Heart:
ventricular septal defect

Cardiovascular Vascular:
pulmonary artery hypoplasia
peripheral pulmonary stenosis
arterial hypertension

Skeletal Hands:
short thumbs
variable shortening of terminal phalanges (brachytelephalangy)
premature fusion of phalangeal epiphyses
interdigital webbing, mild

Growth Height:
stature below 25th percentile

Respiratory Larynx:
cartilaginous ossification of larynx
tracheobronchial stenosis

Skeletal:
abnormal cartilage ossification (nose, pinnae, larynx, epiglottis, trachea, bronchial rings, costochondral junctions)

Skin Nails Hair Skin:
erythematous, irregular macular lesions without induration on dorsum of hands, neck, and trunk

Prenatal Manifestations Delivery:
increased risk of spontaneous abortion

Head And Neck Nose:
depressed nasal bridge
small alae nasi
cartilaginous ossification of nose

Voice:
nasal speech

Respiratory Nasopharynx:
chronic sinusitis

Respiratory Airways:
obstructive lung disease
recurrent bronchitis
cartilaginous ossification of trachea and bronchi
bullous emphysema

Skeletal Feet:
short halluces

Head And Neck Ears:
hearing loss (sensorineural, mixed, and conductive)
large, prominent pinnae
pale, stiff pinnae
progressive cartilaginous ossification of pinnae
recurrent episodes of otitis media

Chest Ribs Sternum Clavicles And Scapulae:
cartilaginous ossification of rib

Skeletal Limbs:
epiphyseal stippling (infancy)

Skin Nails Hair Skin Histology:
absence of elastic fibers in dermis

Clinical features from OMIM:

245150

UMLS symptoms related to Keutel Syndrome:


seizures

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

27 (show all 15)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-101 9.53 BMP2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.53 BMP2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.53 MGP
4 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.53 MGP
5 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.53 MGP
6 Increased shRNA abundance (Z-score > 2) GR00366-A-156 9.53 BMP2 MGP
7 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.53 MGP
8 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.53 BMP2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-22 9.53 MGP
10 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.53 BMP2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.53 MGP
12 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.53 MGP
13 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.53 MGP
14 Increased shRNA abundance (Z-score > 2) GR00366-A-90 9.53 MGP
15 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.53 MGP

MGI Mouse Phenotypes related to Keutel Syndrome:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 8.8 BMP2 GLA MGP

Drugs & Therapeutics for Keutel Syndrome

Search Clinical Trials , NIH Clinical Center for Keutel Syndrome

Genetic Tests for Keutel Syndrome

Genetic tests related to Keutel Syndrome:

# Genetic test Affiliating Genes
1 Keutel Syndrome 30 MGP

Anatomical Context for Keutel Syndrome

MalaCards organs/tissues related to Keutel Syndrome:

42
Trachea, Bone, Skin

Publications for Keutel Syndrome

Articles related to Keutel Syndrome:

(show all 26)
# Title Authors Year
1
A Novel MGP Gene Mutation Causing Keutel Syndrome in a Brazilian Patient. ( 29928182 )
2018
2
CLINICAL VARIABILITY IN TWO SISTERS WITH KEUTEL SYNDROME DUE TO A HOMOZYGOUS MUTATION IN MGP GENE. ( 26349188 )
2015
3
A rare cause of dyspnea in emergency medicine: Keutel syndrome. ( 26462901 )
2015
4
Keutel syndrome: Augmentation of the nose with serial fat grafting. ( 26981492 )
2015
5
Keutel syndrome: report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis. ( 24458983 )
2014
6
Long term follow-up of four patients with Keutel syndrome. ( 25123378 )
2014
7
Neuroimaging findings in children with Keutel syndrome. ( 23917590 )
2014
8
A case of Keutel syndrome diagnosed in the neonatal period: associated with Binder phenotype. ( 22611639 )
2012
9
Tracheobronchial stenosis in Keutel syndrome. ( 23024086 )
2012
10
Circulating matrix I^-carboxyglutamate protein (MGP) species are refractory to vitaminA K treatment in a new case of Keutel syndrome. ( 21435166 )
2011
11
Keutel syndrome in a patient presenting with hearing loss. ( 21090163 )
2010
12
Petrified ears in a patient with Keutel syndrome: temporal bone CT findings. ( 16328322 )
2006
13
Keutel syndrome with overlapping features of cutis laxa: a new variant. ( 16642510 )
2006
14
Tracheobronchial calcification associated with Keutel syndrome. ( 17290573 )
2006
15
A novel MGP mutation in a consanguineous family: review of the clinical and molecular characteristics of Keutel syndrome. ( 15810001 )
2005
16
Brachytelephalangy with sparing of the fifth distal phalanx: a feature highly suggestive of Keutel syndrome. ( 12612818 )
2003
17
Tracheobronchial stenosis in Keutel syndrome. ( 11405537 )
2001
18
Follow-up of an adult with Keutel syndrome. ( 10377017 )
1999
19
Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. ( 9916809 )
1999
20
Picture of the month. Keutel syndrome. ( 10401814 )
1999
21
Keutel syndrome and miscarriages. ( 10096599 )
1999
22
Keutel syndrome: further characterization and review. ( 9674914 )
1998
23
The Keutel syndrome. Report of a case and review of the literature. ( 8414764 )
1993
24
Keutel syndrome: a report of four cases. ( 2515061 )
1989
25
Keutel syndrome: clinical report and literature review. ( 3717211 )
1986
26
Calcification of cartilages, brachytelephalangy and peripheral pulmonary stenosis. Confirmation of the Keutel syndrome. ( 6468443 )
1984

Variations for Keutel Syndrome

ClinVar genetic disease variations for Keutel Syndrome:

6 (show top 50) (show all 58)
# Gene Variation Type Significance SNP ID Assembly Location
1 MGP NM_000900.4(MGP): c.23C> T (p.Ala8Val) single nucleotide variant Benign/Likely benign rs142330429 GRCh37 Chromosome 12, 15038703: 15038703
2 MGP NM_000900.4(MGP): c.23C> T (p.Ala8Val) single nucleotide variant Benign/Likely benign rs142330429 GRCh38 Chromosome 12, 14885769: 14885769
3 MGP NM_001190839.2(MGP): c.43delG (p.Val15Terfs) deletion Pathogenic rs730880321 GRCh37 Chromosome 12, 15038683: 15038683
4 MGP NM_001190839.2(MGP): c.43delG (p.Val15Terfs) deletion Pathogenic rs730880321 GRCh38 Chromosome 12, 14885749: 14885749
5 MGP NM_001190839.2(MGP): c.137-2A> G single nucleotide variant Pathogenic rs112518413 GRCh37 Chromosome 12, 15037181: 15037181
6 MGP NM_001190839.2(MGP): c.137-2A> G single nucleotide variant Pathogenic rs112518413 GRCh38 Chromosome 12, 14884247: 14884247
7 MGP NM_001190839.2(MGP): c.162T> A (p.Tyr54Ter) single nucleotide variant Pathogenic rs730880322 GRCh37 Chromosome 12, 15037154: 15037154
8 MGP NM_001190839.2(MGP): c.162T> A (p.Tyr54Ter) single nucleotide variant Pathogenic rs730880322 GRCh38 Chromosome 12, 14884220: 14884220
9 MGP NM_000900.4(MGP): c.94+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs111320759 GRCh37 Chromosome 12, 15037146: 15037146
10 MGP NM_000900.4(MGP): c.94+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs111320759 GRCh38 Chromosome 12, 14884212: 14884212
11 MGP NM_000900.4(MGP): c.304A> G (p.Thr102Ala) single nucleotide variant Benign rs4236 GRCh37 Chromosome 12, 15035081: 15035081
12 MGP NM_000900.4(MGP): c.304A> G (p.Thr102Ala) single nucleotide variant Benign rs4236 GRCh38 Chromosome 12, 14882147: 14882147
13 MGP NM_000900.4(MGP): c.*140T> C single nucleotide variant Uncertain significance rs148802642 GRCh38 Chromosome 12, 14881999: 14881999
14 MGP NM_000900.4(MGP): c.*140T> C single nucleotide variant Uncertain significance rs148802642 GRCh37 Chromosome 12, 15034933: 15034933
15 MGP NM_000900.4(MGP): c.-117C> T single nucleotide variant Uncertain significance rs569710471 GRCh38 Chromosome 12, 14885908: 14885908
16 MGP NM_000900.4(MGP): c.-117C> T single nucleotide variant Uncertain significance rs569710471 GRCh37 Chromosome 12, 15038842: 15038842
17 MGP NM_000900.4(MGP): c.*755G> T single nucleotide variant Likely benign rs142773584 GRCh37 Chromosome 12, 15034318: 15034318
18 MGP NM_000900.4(MGP): c.*755G> T single nucleotide variant Likely benign rs142773584 GRCh38 Chromosome 12, 14881384: 14881384
19 MGP NM_000900.4(MGP): c.*604A> G single nucleotide variant Uncertain significance rs114512785 GRCh38 Chromosome 12, 14881535: 14881535
20 MGP NM_000900.4(MGP): c.*604A> G single nucleotide variant Uncertain significance rs114512785 GRCh37 Chromosome 12, 15034469: 15034469
21 MGP NM_000900.4(MGP): c.*251T> C single nucleotide variant Uncertain significance rs886049105 GRCh38 Chromosome 12, 14881888: 14881888
22 MGP NM_000900.4(MGP): c.*251T> C single nucleotide variant Uncertain significance rs886049105 GRCh37 Chromosome 12, 15034822: 15034822
23 MGP NM_000900.4(MGP): c.234T> C (p.Leu78=) single nucleotide variant Uncertain significance rs149084241 GRCh38 Chromosome 12, 14882217: 14882217
24 MGP NM_000900.4(MGP): c.234T> C (p.Leu78=) single nucleotide variant Uncertain significance rs149084241 GRCh37 Chromosome 12, 15035151: 15035151
25 MGP NM_000900.4(MGP): c.207T> C (p.Asn69=) single nucleotide variant Uncertain significance rs186013880 GRCh38 Chromosome 12, 14882244: 14882244
26 MGP NM_000900.4(MGP): c.207T> C (p.Asn69=) single nucleotide variant Uncertain significance rs186013880 GRCh37 Chromosome 12, 15035178: 15035178
27 MGP NM_000900.4(MGP): c.62-9delT deletion Likely benign rs11393307 GRCh38 Chromosome 12, 14884254: 14884254
28 MGP NM_000900.4(MGP): c.62-9delT deletion Likely benign rs11393307 GRCh37 Chromosome 12, 15037188: 15037188
29 MGP NM_000900.4(MGP): c.46G> A (p.Val16Ile) single nucleotide variant Uncertain significance rs868750856 GRCh38 Chromosome 12, 14885746: 14885746
30 MGP NM_000900.4(MGP): c.46G> A (p.Val16Ile) single nucleotide variant Uncertain significance rs868750856 GRCh37 Chromosome 12, 15038680: 15038680
31 MGP NM_000900.4(MGP): c.-63G> A single nucleotide variant Benign rs1800801 GRCh38 Chromosome 12, 14885854: 14885854
32 MGP NM_000900.4(MGP): c.-63G> A single nucleotide variant Benign rs1800801 GRCh37 Chromosome 12, 15038788: 15038788
33 MGP NM_000900.4(MGP): c.*538C> G single nucleotide variant Uncertain significance rs139069321 GRCh38 Chromosome 12, 14881601: 14881601
34 MGP NM_000900.4(MGP): c.*538C> G single nucleotide variant Uncertain significance rs139069321 GRCh37 Chromosome 12, 15034535: 15034535
35 MGP NM_000900.4(MGP): c.*476T> C single nucleotide variant Uncertain significance rs184916517 GRCh38 Chromosome 12, 14881663: 14881663
36 MGP NM_000900.4(MGP): c.*476T> C single nucleotide variant Uncertain significance rs184916517 GRCh37 Chromosome 12, 15034597: 15034597
37 MGP NM_000900.4(MGP): c.*455delG deletion Uncertain significance rs886049103 GRCh38 Chromosome 12, 14881684: 14881684
38 MGP NM_000900.4(MGP): c.*455delG deletion Uncertain significance rs886049103 GRCh37 Chromosome 12, 15034618: 15034618
39 MGP NM_000900.4(MGP): c.-66C> A single nucleotide variant Uncertain significance rs150994762 GRCh38 Chromosome 12, 14885857: 14885857
40 MGP NM_000900.4(MGP): c.-66C> A single nucleotide variant Uncertain significance rs150994762 GRCh37 Chromosome 12, 15038791: 15038791
41 MGP NM_000900.4(MGP): c.*615A> G single nucleotide variant Likely benign rs34181533 GRCh37 Chromosome 12, 15034458: 15034458
42 MGP NM_000900.4(MGP): c.*615A> G single nucleotide variant Likely benign rs34181533 GRCh38 Chromosome 12, 14881524: 14881524
43 MGP NM_000900.4(MGP): c.*552A> T single nucleotide variant Benign rs1049897 GRCh38 Chromosome 12, 14881587: 14881587
44 MGP NM_000900.4(MGP): c.*552A> T single nucleotide variant Benign rs1049897 GRCh37 Chromosome 12, 15034521: 15034521
45 MGP NM_000900.4(MGP): c.*343G> A single nucleotide variant Likely benign rs35112962 GRCh38 Chromosome 12, 14881796: 14881796
46 MGP NM_000900.4(MGP): c.*343G> A single nucleotide variant Likely benign rs35112962 GRCh37 Chromosome 12, 15034730: 15034730
47 MGP NM_000900.4(MGP): c.*339T> C single nucleotide variant Likely benign rs150038879 GRCh38 Chromosome 12, 14881800: 14881800
48 MGP NM_000900.4(MGP): c.*339T> C single nucleotide variant Likely benign rs150038879 GRCh37 Chromosome 12, 15034734: 15034734
49 MGP NM_000900.4(MGP): c.*315dup duplication Uncertain significance rs886049104 GRCh38 Chromosome 12, 14881824: 14881824
50 MGP NM_000900.4(MGP): c.*315dup duplication Uncertain significance rs886049104 GRCh37 Chromosome 12, 15034758: 15034758

Expression for Keutel Syndrome

Search GEO for disease gene expression data for Keutel Syndrome.

Pathways for Keutel Syndrome

GO Terms for Keutel Syndrome

Cellular components related to Keutel Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 8.8 BMP2 GLA MGP

Biological processes related to Keutel Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ossification GO:0001503 8.96 BMP2 MGP
2 cartilage development GO:0051216 8.62 BMP2 MGP

Molecular functions related to Keutel Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 8.62 BMP2 GLA

Sources for Keutel Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....