MCID: SNG014
MIFTS: 36

Singleton-Merten Syndrome

Categories: Blood diseases, Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Oral diseases, Rare diseases

Aliases & Classifications for Singleton-Merten Syndrome

MalaCards integrated aliases for Singleton-Merten Syndrome:

Name: Singleton-Merten Syndrome 20 58 36
Widened Medullary Cavities of Bone, Aortic Calcification, Abnormal Dentition, and Muscular Weakness 20 6
Singleton-Merten Dysplasia 20 58
Syndrome of Widened Medullary Cavities of the Metacarpals and Phalanges, Aortic Calcification and Abnormal Dentition 20
Syndrome, Singleton-Merten 39
Merten-Singleton Syndrome 20
Singleton Merten Syndrome 71
Sm Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
singleton-merten dysplasia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

Classifications:

Orphanet: 58  
Rare systemic and rhumatological diseases
Rare bone diseases
Developmental anomalies during embryogenesis
Rare immunological diseases


External Ids:

KEGG 36 H01571
ICD10 via Orphanet 33 Q78.8
UMLS via Orphanet 72 C0432254
Orphanet 58 ORPHA85191
UMLS 71 C0432254

Summaries for Singleton-Merten Syndrome

GARD : 20 Singleton-Merten syndrome is a very rare disease that affect many organs. The main features are tooth abnormalities with gum infection; calcifications in the aorta artery and in certain valves of the heart (i.e., aortic and mitral valves); and progressive thinning and weakening of the bones (osteoporosis), especially in the upper and back portions of the skull. Other findings may include neurologic problems, generalized short stature, muscle weakness; poor muscle tone (hypotonia); progressive wasting of the muscles (muscle atrophy); heart arrhythmia, growth and developmental delay; skin problems such as psoriasis; malformation of the hips and/or feet and limbs or fingers, joint problems, tendon rupture, distinct facial features, and vision problems due to glaucoma. Severe systemic lupus erythematosus can also occur with Singleton-Merten syndrome. Singleton-Merten syndrome is caused by mutations in the IFIH1 gene, and in the DDX58 genes (which causes anatypical form of Singleton-Merten syndrome where there are no teeth problems). Inheritance is autosomal dominant, but it may also occur sporadically (in individuals with no history of the condition in their family). Commonly, people with type I interferonopathies are treated with high doses of intravenous methylprednisolone, oral prednisone and intravenous immunoglobulins during the acute phases with often only partial control of the flares. There are studies trying to find a more effective treatment. The genes causing Singeleton-Merten syndrome can activate type I interferon (IFN1) responses. Diseases related to INF1 are known as type I interferonopathies. Type I interferonopathies are a group of rheumatic diseases that are frequently severe and have an early-onset. These diseases include Aicardi-Goutieres syndrome, familial chilblain lupus, spondyloenchondrodysplasia, the proteasome associated autoinflammatory syndromes, IFN-stimulated gene 15 (ISG15) deficiency, Singleton-Merten syndrome, STING-associated vasculopathy with onset in infancy (SAVI).

MalaCards based summary : Singleton-Merten Syndrome, also known as widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness, is related to psoriasis and singleton-merten syndrome 2. An important gene associated with Singleton-Merten Syndrome is DDX58 (DExD/H-Box Helicase 58), and among its related pathways/superpathways are Deubiquitination and Measles. Affiliated tissues include heart, bone and smooth muscle.

KEGG : 36 Singleton-Merten syndrome (SMS) is a rare autosomal-dominant multisystem disorder characterized by early and extreme aortic and valvular calcification, dental anomalies (early-onset periodontitis and root resorption), osteopenia, and acro-osteolysis. A gain-of-function mutation in interferon induced with helicase C domain 1 (IFIH1), encoding melanoma differentiation-associated protein 5 (MDA5), causes SMS through dysregulation of the human innate immune response. DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

Wikipedia : 74 Singleton Merten Syndrome is an autosomal dominant genetic disorder with variable expression with an... more...

Related Diseases for Singleton-Merten Syndrome

Diseases in the Singleton-Merten Syndrome family:

Singleton-Merten Syndrome 1 Singleton-Merten Syndrome 2

Diseases related to Singleton-Merten Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 38)
# Related Disease Score Top Affiliating Genes
1 psoriasis 29.4 IFIH1 DDX58
2 singleton-merten syndrome 2 11.9
3 singleton-merten syndrome 1 11.8
4 root resorption 10.4
5 acroosteolysis 10.3
6 autoimmune disease 10.3
7 periodontitis 10.3
8 tendinitis 10.1
9 arterial calcification of infancy 10.1
10 basal ganglia calcification 10.1
11 melanoma 10.1
12 arthropathy 10.1
13 pustulosis of palm and sole 10.1
14 aortic valve insufficiency 10.1
15 nephrolithiasis 10.1
16 spasticity 10.1
17 croup 9.8 IFIH1 DDX58
18 sting-associated vasculopathy with onset in infancy 9.8 IFIH1 DDX58
19 noonan syndrome 7 9.8 IFIH1 DDX58
20 noonan syndrome 6 9.8 IFIH1 DDX58
21 type 1 diabetes mellitus 20 9.8 IFIH1 DDX58
22 lassa fever 9.8 IFIH1 DDX58
23 chilblain lupus 1 9.8 IFIH1 DDX58
24 herpangina 9.8 IFIH1 DDX58
25 coronavirus infectious disease 9.8 IFIH1 DDX58
26 microphthalmia with limb anomalies 9.8 IFIH1 DDX58
27 west nile virus 9.8 IFIH1 DDX58
28 dengue virus 9.8 IFIH1 DDX58
29 severe acute respiratory syndrome 9.8 IFIH1 DDX58
30 measles 9.8 IFIH1 DDX58
31 aicardi-goutieres syndrome 9.8 IFIH1 DDX58
32 hepatitis c virus 9.7 IFIH1 DDX58
33 hepatitis 9.7 IFIH1 DDX58
34 mouth disease 9.7 IFIH1 DDX58
35 viral infectious disease 9.7 IFIH1 DDX58
36 rasopathy 9.7 IFIH1 DDX58
37 herpes simplex 9.6 IFIH1 DDX58
38 influenza 9.6 IFIH1 DDX58

Graphical network of the top 20 diseases related to Singleton-Merten Syndrome:



Diseases related to Singleton-Merten Syndrome

Symptoms & Phenotypes for Singleton-Merten Syndrome

Drugs & Therapeutics for Singleton-Merten Syndrome

Search Clinical Trials , NIH Clinical Center for Singleton-Merten Syndrome

Genetic Tests for Singleton-Merten Syndrome

Anatomical Context for Singleton-Merten Syndrome

MalaCards organs/tissues related to Singleton-Merten Syndrome:

40
Heart, Bone, Smooth Muscle

Publications for Singleton-Merten Syndrome

Articles related to Singleton-Merten Syndrome:

(show all 33)
# Title Authors PMID Year
1
A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome. 6 61
25620204 2015
2
Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome. 61 6
25620203 2015
3
Singleton-merten syndrome and impaired cardiac function. 6 61
21070929 2010
4
Further evidence for specific IFIH1 mutation as a cause of Singleton-Merten syndrome with phenotypic heterogeneity. 61 20
28319323 2017
5
DDX58(RIG-I)-related disease is associated with tissue-specific interferon pathway activation. 61
33495304 2021
6
Aicardi-Goutières syndrome-like encephalitis in mutant mice with constitutively active MDA5. 61
33165593 2020
7
Psoriasis-like skin disorder in transgenic mice expressing a RIG-I Singleton-Merten syndrome variant. 61
33119735 2020
8
A case of Singleton-Merten syndrome without cardiac involvement harboring a novel IFIH1 variant. 61
32202700 2020
9
Genetic and phenotypic spectrum associated with IFIH1 gain-of-function. 61
31898846 2020
10
Toward a better understanding of type I interferonopathies: a brief summary, update and beyond. 61
31377974 2020
11
Singleton-Merten Syndrome-like Skeletal Abnormalities in Mice with Constitutively Activated MDA5. 61
31366715 2019
12
R516Q mutation in Melanoma differentiation-associated protein 5 (MDA5) and its pathogenic role towards rare Singleton-Merten syndrome; a signature associated molecular dynamics study. 61
29429386 2019
13
DDX58 and Classic Singleton-Merten Syndrome. 61
30574673 2019
14
Transcatheter Aortic Valve Replacement for Severe Aortic Regurgitation in Singleton-Merten Syndrome. 61
30343025 2018
15
RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization. 61
30270105 2018
16
Calcification Induced by Type I Interferon in Human Aortic Valve Interstitial Cells Is Larger in Males and Blunted by a Janus Kinase Inhibitor. 61
30026273 2018
17
Unified mechanisms for self-RNA recognition by RIG-I Singleton-Merten syndrome variants. 61
30047865 2018
18
A GTPase-activating protein-binding protein (G3BP1)/antiviral protein relay conveys arteriosclerotic Wnt signals in aortic smooth muscle cells. 61
29626090 2018
19
Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy. 61
28605144 2017
20
Inherited Arterial Calcification Syndromes: Etiologies and Treatment Concepts. 61
28585220 2017
21
MDA5-Associated Neuroinflammation and the Singleton-Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum. 61
28475458 2017
22
RIG-I-Like Receptor Signaling in Singleton-Merten Syndrome. 61
28955379 2017
23
Singleton Merten Syndrome: A Rare Cause of Early Onset Aortic Stenosis. 61
28321341 2017
24
Novel interferonopathies associated with mutations in RIG-I like receptors. 61
26993858 2016
25
Unusual cutaneous features associated with a heterozygous gain-of-function mutation in IFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes. 61
26284909 2015
26
ATP hydrolysis by the viral RNA sensor RIG-I prevents unintentional recognition of self-RNA. 61
26609812 2015
27
[Type I interferonopathies]. 61
26363997 2015
28
Long term clinical outcome of dental implants placed in a patient with Singleton-Merten syndrome. 61
26043888 2015
29
Progressive supra-aortic stenosis in a young adult with the findings of Singleton Merten Syndrome. 61
25193816 2014
30
Establishment of Singleton-Merten syndrome pulp cells: evidence of mineralization dysregulation. 61
25158182 2014
31
Singleton-Merten syndrome: an autosomal dominant disorder with variable expression. 61
23322711 2013
32
[Singleton-Merten syndrome]. 61
11528940 2001
33
A syndrome of widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness (the Singleton-Merten syndrome). 61
175395 1976

Variations for Singleton-Merten Syndrome

ClinVar genetic disease variations for Singleton-Merten Syndrome:

6 (show top 50) (show all 214)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 IFIH1 NM_022168.4(IFIH1):c.2465G>A (p.Arg822Gln) SNV Pathogenic 189338 rs376048533 2:163128887-163128887 2:162272377-162272377
2 DDX58 NM_014314.4(DDX58):c.1118A>C (p.Glu373Ala) SNV Pathogenic 189344 rs786204847 9:32488037-32488037 9:32488039-32488039
3 DDX58 NM_014314.4(DDX58):c.803G>T (p.Cys268Phe) SNV Pathogenic 189345 rs786204848 9:32488882-32488882 9:32488884-32488884
4 IFIH1 NM_022168.4(IFIH1):c.2336G>A (p.Arg779His) SNV Pathogenic 137622 rs587777446 2:163130423-163130423 2:162273913-162273913
5 IFIH1 NM_022168.4(IFIH1):c.2465G>A (p.Arg822Gln) SNV Pathogenic 189338 rs376048533 2:163128887-163128887 2:162272377-162272377
6 DDX58 NM_014314.4(DDX58):c.1529A>T (p.Glu510Val) SNV Likely pathogenic 802476 rs1587586052 9:32481447-32481447 9:32481449-32481449
7 IFIH1 NM_022168.4(IFIH1):c.716dup (p.Met240fs) Duplication Likely pathogenic 587596 rs1558875029 2:163163271-163163272 2:162306761-162306762
8 IFIH1 NM_022168.4(IFIH1):c.986T>C (p.Leu329Pro) SNV Likely pathogenic 577615 rs923064561 2:163144754-163144754 2:162288244-162288244
9 IFIH1 NM_022168.4(IFIH1):c.2936T>G (p.Leu979Trp) SNV Likely pathogenic 541770 rs1553696482 2:163123852-163123852 2:162267342-162267342
10 IFIH1 NM_022168.4(IFIH1):c.2402G>A (p.Cys801Tyr) SNV Likely pathogenic 801772 rs1576222807 2:163130357-163130357 2:162273847-162273847
11 IFIH1 NM_022168.4(IFIH1):c.2524G>A (p.Glu842Lys) SNV Conflicting interpretations of pathogenicity 474952 rs79324540 2:163128828-163128828 2:162272318-162272318
12 IFIH1 NM_022168.4(IFIH1):c.1641+1G>C SNV Conflicting interpretations of pathogenicity 261563 rs35337543 2:163136505-163136505 2:162279995-162279995
13 IFIH1 NM_022168.4(IFIH1):c.478A>G (p.Asn160Asp) SNV Conflicting interpretations of pathogenicity 625959 rs74162075 2:163167419-163167419 2:162310909-162310909
14 IFIH1 NM_022168.4(IFIH1):c.1066C>A (p.Pro356Thr) SNV Conflicting interpretations of pathogenicity 541784 rs150317197 2:163144674-163144674 2:162288164-162288164
15 IFIH1 NM_022168.4(IFIH1):c.2362G>A (p.Ala788Thr) SNV Conflicting interpretations of pathogenicity 541788 rs148369169 2:163130397-163130397 2:162273887-162273887
16 IFIH1 NM_022168.4(IFIH1):c.2863C>G (p.Gln955Glu) SNV Conflicting interpretations of pathogenicity 705603 rs144455277 2:163124024-163124024 2:162267514-162267514
17 IFIH1 NM_022168.4(IFIH1):c.1806A>T (p.Glu602Asp) SNV Uncertain significance 665140 rs763549486 2:163134163-163134163 2:162277653-162277653
18 IFIH1 NM_022168.4(IFIH1):c.2793G>A (p.Met931Ile) SNV Uncertain significance 665183 rs1576220013 2:163124611-163124611 2:162268101-162268101
19 IFIH1 NM_022168.4(IFIH1):c.2831A>T (p.Asn944Ile) SNV Uncertain significance 665367 rs1322389017 2:163124056-163124056 2:162267546-162267546
20 IFIH1 NM_022168.4(IFIH1):c.1641+2T>C SNV Uncertain significance 834133 2:163136504-163136504 2:162279994-162279994
21 IFIH1 NM_022168.4(IFIH1):c.1486G>A (p.Ala496Thr) SNV Uncertain significance 834571 2:163137876-163137876 2:162281366-162281366
22 IFIH1 NM_022168.4(IFIH1):c.1303T>A (p.Ser435Thr) SNV Uncertain significance 836508 2:163138879-163138879 2:162282369-162282369
23 IFIH1 NM_022168.4(IFIH1):c.3055del (p.Cys1019fs) Deletion Uncertain significance 836873 2:163123733-163123733 2:162267223-162267223
24 IFIH1 NM_022168.4(IFIH1):c.2216_2222del (p.Thr739fs) Deletion Uncertain significance 837605 2:163133279-163133285 2:162276769-162276775
25 IFIH1 NM_022168.4(IFIH1):c.1589del (p.Asn530fs) Deletion Uncertain significance 837942 2:163136558-163136558 2:162280048-162280048
26 IFIH1 NM_022168.4(IFIH1):c.1558A>G (p.Thr520Ala) SNV Uncertain significance 444523 rs145641024 2:163136589-163136589 2:162280079-162280079
27 IFIH1 NM_022168.4(IFIH1):c.2641A>G (p.Ile881Val) SNV Uncertain significance 842968 2:163124763-163124763 2:162268253-162268253
28 IFIH1 NM_022168.4(IFIH1):c.2788A>G (p.Asn930Asp) SNV Uncertain significance 843149 2:163124616-163124616 2:162268106-162268106
29 IFIH1 NM_022168.4(IFIH1):c.1222G>A (p.Asp408Asn) SNV Uncertain significance 844159 2:163138960-163138960 2:162282450-162282450
30 IFIH1 NM_022168.4(IFIH1):c.1710G>A (p.Met570Ile) SNV Uncertain significance 845324 2:163134770-163134770 2:162278260-162278260
31 IFIH1 NM_022168.4(IFIH1):c.556C>T (p.Arg186Cys) SNV Uncertain significance 845631 2:163167341-163167341 2:162310831-162310831
32 IFIH1 NM_022168.4(IFIH1):c.145A>G (p.Thr49Ala) SNV Uncertain significance 848148 2:163174673-163174673 2:162318163-162318163
33 IFIH1 NM_022168.4(IFIH1):c.1853G>A (p.Arg618Gln) SNV Uncertain significance 849039 2:163134116-163134116 2:162277606-162277606
34 IFIH1 NM_022168.4(IFIH1):c.2191G>T (p.Ala731Ser) SNV Uncertain significance 849273 2:163133310-163133310 2:162276800-162276800
35 IFIH1 NM_022168.4(IFIH1):c.285G>A (p.Met95Ile) SNV Uncertain significance 851462 2:163174533-163174533 2:162318023-162318023
36 IFIH1 NM_022168.4(IFIH1):c.1745C>T (p.Ala582Val) SNV Uncertain significance 852349 2:163134735-163134735 2:162278225-162278225
37 IFIH1 NM_022168.4(IFIH1):c.2616+6G>A SNV Uncertain significance 852801 2:163128730-163128730 2:162272220-162272220
38 IFIH1 NM_022168.4(IFIH1):c.2259T>G (p.His753Gln) SNV Uncertain significance 855667 2:163133242-163133242 2:162276732-162276732
39 IFIH1 NM_022168.4(IFIH1):c.1874A>T (p.His625Leu) SNV Uncertain significance 855752 2:163134095-163134095 2:162277585-162277585
40 IFIH1 NM_022168.4(IFIH1):c.1927G>T (p.Asp643Tyr) SNV Uncertain significance 855766 2:163134042-163134042 2:162277532-162277532
41 IFIH1 NM_022168.4(IFIH1):c.1535A>G (p.Asn512Ser) SNV Uncertain significance 857407 2:163136612-163136612 2:162280102-162280102
42 IFIH1 NM_022168.4(IFIH1):c.2428G>A (p.Val810Ile) SNV Uncertain significance 857685 2:163130331-163130331 2:162273821-162273821
43 IFIH1 NM_022168.4(IFIH1):c.2035_2036del (p.Leu679fs) Deletion Uncertain significance 638319 rs774076578 2:163133933-163133934 2:162277423-162277424
44 IFIH1 NM_022168.4(IFIH1):c.229C>A (p.Arg77=) SNV Uncertain significance 858398 2:163174589-163174589 2:162318079-162318079
45 IFIH1 NM_022168.4(IFIH1):c.2561T>G (p.Met854Arg) SNV Uncertain significance 858942 2:163128791-163128791 2:162272281-162272281
46 IFIH1 NM_022168.4(IFIH1):c.217C>T (p.Leu73Phe) SNV Uncertain significance 859413 2:163174601-163174601 2:162318091-162318091
47 IFIH1 NM_022168.4(IFIH1):c.1153T>C (p.Tyr385His) SNV Uncertain significance 860770 2:163139029-163139029 2:162282519-162282519
48 IFIH1 NM_022168.4(IFIH1):c.2642T>C (p.Ile881Thr) SNV Uncertain significance 860887 2:163124762-163124762 2:162268252-162268252
49 IFIH1 NM_022168.4(IFIH1):c.2392A>G (p.Ile798Val) SNV Uncertain significance 861040 2:163130367-163130367 2:162273857-162273857
50 IFIH1 NM_022168.4(IFIH1):c.1962T>G (p.Cys654Trp) SNV Uncertain significance 863053 2:163134007-163134007 2:162277497-162277497

Expression for Singleton-Merten Syndrome

Search GEO for disease gene expression data for Singleton-Merten Syndrome.

Pathways for Singleton-Merten Syndrome

Pathways related to Singleton-Merten Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.12 IFIH1 DDX58
2
Show member pathways
12.08 IFIH1 DDX58
3 12.02 IFIH1 DDX58
4 11.77 IFIH1 DDX58
5
Show member pathways
11.66 IFIH1 DDX58
6
Show member pathways
11.45 IFIH1 DDX58
7 10.19 IFIH1 DDX58

GO Terms for Singleton-Merten Syndrome

Biological processes related to Singleton-Merten Syndrome according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 innate immune response GO:0045087 9.55 IFIH1 DDX58
2 viral process GO:0016032 9.54 IFIH1 DDX58
3 protein deubiquitination GO:0016579 9.52 IFIH1 DDX58
4 defense response to virus GO:0051607 9.51 IFIH1 DDX58
5 response to virus GO:0009615 9.49 IFIH1 DDX58
6 positive regulation of interleukin-6 production GO:0032755 9.48 IFIH1 DDX58
7 positive regulation of tumor necrosis factor production GO:0032760 9.46 IFIH1 DDX58
8 positive regulation of interferon-beta production GO:0032728 9.43 IFIH1 DDX58
9 negative regulation of type I interferon production GO:0032480 9.4 IFIH1 DDX58
10 positive regulation of interferon-alpha production GO:0032727 9.37 IFIH1 DDX58
11 cellular response to exogenous dsRNA GO:0071360 9.32 IFIH1 DDX58
12 positive regulation of response to cytokine stimulus GO:0060760 9.26 IFIH1 DDX58
13 detection of virus GO:0009597 9.16 IFIH1 DDX58
14 cytoplasmic pattern recognition receptor signaling pathway in response to virus GO:0039528 8.96 IFIH1 DDX58
15 regulation of type III interferon production GO:0034344 8.62 IFIH1 DDX58

Molecular functions related to Singleton-Merten Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 helicase activity GO:0004386 9.26 IFIH1 DDX58
2 RNA helicase activity GO:0003724 9.16 IFIH1 DDX58
3 double-stranded RNA binding GO:0003725 8.96 IFIH1 DDX58
4 single-stranded RNA binding GO:0003727 8.62 IFIH1 DDX58

Sources for Singleton-Merten 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
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44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
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53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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