MCID: SNG014
MIFTS: 30

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 52 58 36
Singleton-Merten Dysplasia 52 58
Syndrome of Widened Medullary Cavities of the Metacarpals and Phalanges, Aortic Calcification and Abnormal Dentition 52
Widened Medullary Cavities of Bone, Aortic Calcification, Abnormal Dentition, and Muscular Weakness 52
Syndrome, Singleton-Merten 39
Merten-Singleton Syndrome 52
Singleton Merten Syndrome 71
Sm Syndrome 52

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

NIH Rare Diseases : 52 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 singleton-merten dysplasia, is related to chilblain lupus 1 and psoriasis. An important gene associated with Singleton-Merten Syndrome is IFIH1 (Interferon Induced With Helicase C Domain 1), and among its related pathways/superpathways are Deubiquitination and Measles. Affiliated tissues include bone, heart and skin.

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

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
Bone, Heart, Skin, Smooth Muscle

Publications for Singleton-Merten Syndrome

Articles related to Singleton-Merten Syndrome:

(show all 30)
# 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. 6 61
25620203 2015
3
Singleton-merten syndrome and impaired cardiac function. 61 6
21070929 2010
4
Further evidence for specific IFIH1 mutation as a cause of Singleton-Merten syndrome with phenotypic heterogeneity. 52 61
28319323 2017
5
A case of Singleton-Merten syndrome without cardiac involvement harboring a novel IFIH1 variant. 61
32202700 2020
6
Genetic and phenotypic spectrum associated with IFIH1 gain-of-function. 61
31898846 2020
7
Toward a better understanding of type I interferonopathies: a brief summary, update and beyond. 61
31377974 2020
8
Singleton-Merten Syndrome-like Skeletal Abnormalities in Mice with Constitutively Activated MDA5. 61
31366715 2019
9
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
10
DDX58 and Classic Singleton-Merten Syndrome. 61
30574673 2019
11
Transcatheter Aortic Valve Replacement for Severe Aortic Regurgitation in Singleton-Merten Syndrome. 61
30343025 2018
12
RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization. 61
30270105 2018
13
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
14
Unified mechanisms for self-RNA recognition by RIG-I Singleton-Merten syndrome variants. 61
30047865 2018
15
A GTPase-activating protein-binding protein (G3BP1)/antiviral protein relay conveys arteriosclerotic Wnt signals in aortic smooth muscle cells. 61
29626090 2018
16
Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy. 61
28605144 2017
17
Inherited Arterial Calcification Syndromes: Etiologies and Treatment Concepts. 61
28585220 2017
18
MDA5-Associated Neuroinflammation and the Singleton-Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum. 61
28475458 2017
19
Singleton Merten Syndrome: A Rare Cause of Early Onset Aortic Stenosis. 61
28321341 2017
20
RIG-I-Like Receptor Signaling in Singleton-Merten Syndrome. 61
28955379 2017
21
Novel interferonopathies associated with mutations in RIG-I like receptors. 61
26993858 2016
22
Unusual cutaneous features associated with a heterozygous gain-of-function mutation in IFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes. 61
26284909 2015
23
[Type I interferonopathies]. 61
26363997 2015
24
ATP hydrolysis by the viral RNA sensor RIG-I prevents unintentional recognition of self-RNA. 61
26609812 2015
25
Long term clinical outcome of dental implants placed in a patient with Singleton-Merten syndrome. 61
26043888 2015
26
Progressive supra-aortic stenosis in a young adult with the findings of Singleton Merten Syndrome. 61
25193816 2014
27
Establishment of Singleton-Merten syndrome pulp cells: evidence of mineralization dysregulation. 61
25158182 2014
28
Singleton-Merten syndrome: an autosomal dominant disorder with variable expression. 61
23322711 2013
29
[Singleton-Merten syndrome]. 61
11528940 2001
30
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

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
12.07 IFIH1 DDX58
3 12.01 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 17)
# Name GO ID Score Top Affiliating Genes
1 innate immune response GO:0045087 9.57 IFIH1 DDX58
2 viral process GO:0016032 9.56 IFIH1 DDX58
3 protein deubiquitination GO:0016579 9.55 IFIH1 DDX58
4 defense response to virus GO:0051607 9.54 IFIH1 DDX58
5 response to virus GO:0009615 9.52 IFIH1 DDX58
6 positive regulation of interleukin-6 secretion GO:2000778 9.51 IFIH1 DDX58
7 negative regulation of type I interferon production GO:0032480 9.49 IFIH1 DDX58
8 positive regulation of interferon-beta production GO:0032728 9.48 IFIH1 DDX58
9 positive regulation of tumor necrosis factor secretion GO:1904469 9.46 IFIH1 DDX58
10 cellular response to exogenous dsRNA GO:0071360 9.43 IFIH1 DDX58
11 positive regulation of interferon-alpha production GO:0032727 9.4 IFIH1 DDX58
12 positive regulation of interferon-alpha secretion GO:1902741 9.37 IFIH1 DDX58
13 positive regulation of response to cytokine stimulus GO:0060760 9.32 IFIH1 DDX58
14 detection of virus GO:0009597 9.26 IFIH1 DDX58
15 positive regulation of interferon-beta secretion GO:0035549 9.16 IFIH1 DDX58
16 cytoplasmic pattern recognition receptor signaling pathway in response to virus GO:0039528 8.96 IFIH1 DDX58
17 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
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9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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36 KEGG
37 LifeMap
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44 MESH via Orphanet
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48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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