MCID: INF049
MIFTS: 49

Infantile Myofibromatosis

Categories: Rare diseases, Genetic diseases, Neuronal diseases, Skin diseases, Cancer diseases

Aliases & Classifications for Infantile Myofibromatosis

MalaCards integrated aliases for Infantile Myofibromatosis:

Name: Infantile Myofibromatosis 12 72 49 55 36 28 51 14 69
Myofibromatosis 69

Characteristics:

Orphanet epidemiological data:

55
infantile myofibromatosis
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

Classifications:



Summaries for Infantile Myofibromatosis

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2591Disease definitionInfantile myofibromatosis (IM) is a rare benign soft tissuetumor characterized by the development of nodules in the skin, striated muscles, bones, and in exceptional cases, visceral organs, leading to a broad spectrum of clinical symptoms. IM contains myofibroblasts.EpidemiologyThe estimated prevalence is 1/150,000 live births.Clinical descriptionIM presents at birth or develops shortly thereafter, with 90% of cases occurring before the age of 2 years. IM is characterized by solitary or multiple nodules that are firm, flesh-colored to purple (myofibromes), and usually painless (except in case of compression of adjacent nerves). Tumors are located in the skin, subcutaneous tissue, striated muscles and in exceptional cases, visceral organs or bones. There are 4 patterns of clinical presentation: solitary (single lesion affecting the skin and/or muscles in the head, neck, or trunk (75% cases)); congenital multiple (multicentric limited to skin and muscles); congenital multiple with single visceral involvement; and congenital multiple with multiple visceral involvement (multiple lesions of skin and/or muscles, bones, lungs, heart and gastrointestinal tract).EtiologyMost of these tumors are sporadic and isolated. Rare familial cases of IM have been described and 2 genes have been identified as disease causing: PDGFRB and NOTCH3 which encode PDGFRB and NOTCH3 respectively. PDGFRB is a tyrosine kinase receptor for platelet derived growth factors which are mitogens for cells of mesenchymal origin. PDGFRB expression is up regulated by NOTCH3. This suggests that genetic defects in the 2 genes are involved in the same mechanism.Diagnostic methodsDiagnosis is based partly on family history and physical examination. Myofibromes are identified through ultrasound (mass with an anechoic center), MRI (low signal on T1-weighted imaging and high or low signal intensity areas on T2-weighted imaging) and less frequently CT (mass with peripheral enhancement and calcifications). Histopathology remains the gold standard for the diagnosis of IM. Biopsy reveals interlacing fascicles of spindle cells (myofibroblasts) in the periphery, forming nodules separated by collagen tissue with no nuclear atypia. Immunochemistry reveals vimentin and smooth muscle actin expression while vascular markers (S100 and CD34) are negative.Differential diagnosisDifferential diagnosis includes hemangioma, lymphangioma, neurofibroma, infantile fibrosarcoma, Langerhans cell histiocytosis, inflammatory myofibroblastic tumor, desmoid tumors (see these terms), and dermoid or epidermoid tumors.Antenatal diagnosisPrenatal diagnosis is achieved by ultrasound examination.Genetic counselingIM is mostly isolated and sporadic. In cases of familial and multifocal lesions, IM can be inherited as an autosomal recessive or dominant trait (incomplete penetrance and variable expressivity).Management and treatmentDue to the benignity of the lesion, therapies without long term effects are preferred. For lesions affecting the skin and/or muscles, treatment is not recommended and a wait-and-see policy is proposed (tendency towards spontaneous regression). Radical surgical excision is required if: vital organs are involved, lesions are in threatening sites, or lesions are symptomatic. In cases of incomplete resection, re-excision can be proposed later. Standard therapy is methotrexate and vinblastine and is indicated for multifocal progressive lesions. Other treatments such as IFN-alpha or conventional chemotherapy (vincristine, actinomycin D, and cyclophosphamide) should be kept for patients with rapid symptomatic progression because of the long-term risks of secondary malignancy development.PrognosisIn the majority of cases, which lack visceral involvement, prognosis is excellent and spontaneous regression is often observed. On the other hand, the presence of visceral lesions is associated with a significantly poor outcome and a mortality rate of up to 70%, in the absence of therapy. Death is generally related to organ compression and cardiopulmonary and gastrointestinal involvement.Visit the Orphanet disease page for more resources. Last updated: 11/8/2013

MalaCards based summary : Infantile Myofibromatosis, also known as myofibromatosis, is related to myofibromatosis, infantile, 1 and myofibroma, and has symptoms including abnormality of the kidney, gingival fibromatosis and abnormality of the eye. An important gene associated with Infantile Myofibromatosis is PDGFRB (Platelet Derived Growth Factor Receptor Beta), and among its related pathways/superpathways are Notch signaling pathway and PI3K-Akt signaling pathway. Affiliated tissues include bone, skin and lung, and related phenotypes are behavior/neurological and cardiovascular system

Disease Ontology : 12 A connective tissue benign neoplasm that is characterized by the development of benign tumors in the skin, striated muscles, bones, and in exceptional cases, visceral organs.

Wikipedia : 72 Infantile myofibromatosis (also known as \"Congenital generalized fibromatosis,\" and \"Congenital... more...

Related Diseases for Infantile Myofibromatosis

Diseases in the Infantile Myofibromatosis family:

Myofibromatosis, Infantile, 1 Myofibromatosis, Infantile, 2

Diseases related to Infantile Myofibromatosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 109)
# Related Disease Score Top Affiliating Genes
1 myofibromatosis, infantile, 1 32.7 ACTC1 NOTCH3 PDGFRB
2 myofibroma 30.2 DES MB PDGFRB
3 hemangiopericytoma, malignant 29.7 ACTC1 DES VIM
4 fibromatosis 29.6 ACTC1 DES VIM
5 congenital fibrosarcoma 29.2 ACTC1 DES VIM
6 myofibromatosis, infantile, 2 11.8
7 musculoskeletal system benign neoplasm 10.3 CARMIL2 PDGFRB
8 breast rhabdomyosarcoma 10.3 DES MB
9 giant cell myocarditis 10.3 DES MB
10 malignant triton tumor 10.3 DES MB
11 mesenchymoma 10.3 DES MB
12 spindle cell rhabdomyosarcoma 10.3 DES MB
13 bilateral retinoblastoma 10.2 DES MB
14 corneal dystrophy, subepithelial mucinous 10.2 MB PDGFRB
15 adenosarcoma 10.2 DES MB
16 skin glomus tumor 10.2 DES VIM
17 infantile digital fibromatosis 10.2 DES VIM
18 lymphangiomatosis 10.2 DES VIM
19 primitive neuroectodermal tumor of the cervix uteri 10.2 DES VIM
20 epulis 10.2 DES VIM
21 biphasic synovial sarcoma 10.2 DES VIM
22 syringoma 10.2 DES VIM
23 juvenile xanthogranuloma 10.2 DES VIM
24 mesenchymal chondrosarcoma 10.1 DES VIM
25 extraskeletal ewing sarcoma 10.1 DES VIM
26 connective tissue benign neoplasm 10.1 CARMIL2 NDRG4 PDGFRB
27 medullomyoblastoma 10.1 DES MB
28 granular cell tumor 10.1 DES VIM
29 malignant mesenchymoma 10.1 DES MB
30 congenital epulis 10.1 DES VIM
31 embryonal sarcoma 10.1 DES VIM
32 uterine sarcoma 10.1 DES MB PDGFRB
33 benign mesothelioma 10.1 DES VIM
34 myopericytoma 10.1 ACTC1 PDGFRB
35 ovarian fibrothecoma 10.1 ACTC1 DES
36 muscle cancer 10.1 DES MB
37 fibroblastic rheumatism 10.0 ACTC1 DES
38 fibromuscular dysplasia 10.0
39 intussusception 10.0
40 fibrosarcoma 10.0
41 mediastinitis 10.0
42 pulmonary vein stenosis 10.0 ACTC1 DES
43 cystic nephroma 10.0 ACTC1 DES
44 ischemic fasciitis 10.0 ACTC1 DES
45 dedifferentiated liposarcoma 10.0 ACTC1 DES
46 binswanger's disease 10.0 ACTC1 NOTCH3
47 non-langerhans-cell histiocytosis 10.0 ACTC1 DES
48 pericardial mesothelioma 9.9 MB VIM
49 chordoma 9.9 DES VIM
50 epithelioid sarcoma 9.9 MB VIM

Graphical network of the top 20 diseases related to Infantile Myofibromatosis:



Diseases related to Infantile Myofibromatosis

Symptoms & Phenotypes for Infantile Myofibromatosis

Human phenotypes related to Infantile Myofibromatosis:

55 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of the kidney 55 31 occasional (7.5%) Occasional (29-5%) HP:0000077
2 gingival fibromatosis 55 31 frequent (33%) Frequent (79-30%) HP:0000169
3 abnormality of the eye 55 31 occasional (7.5%) Occasional (29-5%) HP:0000478
4 abnormality of the thorax 55 31 frequent (33%) Frequent (79-30%) HP:0000765
5 abnormality of the skull 55 31 frequent (33%) Frequent (79-30%) HP:0000929
6 chondrocalcinosis 55 31 frequent (33%) Frequent (79-30%) HP:0000934
7 abnormality of the metaphysis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000944
8 limitation of joint mobility 55 31 occasional (7.5%) Occasional (29-5%) HP:0001376
9 subcutaneous nodule 55 31 hallmark (90%) Very frequent (99-80%) HP:0001482
10 abnormality of the hair 55 31 frequent (33%) Frequent (79-30%) HP:0001595
11 tracheoesophageal fistula 55 31 occasional (7.5%) Occasional (29-5%) HP:0002575
12 osteolysis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002797
13 neoplasm of the pancreas 55 31 occasional (7.5%) Occasional (29-5%) HP:0002894
14 abnormality of the musculature 55 31 hallmark (90%) Very frequent (99-80%) HP:0003011
15 hypercalcemia 55 31 occasional (7.5%) Occasional (29-5%) HP:0003072
16 hemiplegia/hemiparesis 55 31 occasional (7.5%) Occasional (29-5%) HP:0004374
17 abnormality of the sacrum 55 31 occasional (7.5%) Occasional (29-5%) HP:0005107
18 intestinal obstruction 55 31 occasional (7.5%) Occasional (29-5%) HP:0005214
19 irregular hyperpigmentation 55 31 occasional (7.5%) Occasional (29-5%) HP:0007400
20 neoplasm of the skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0008069
21 bone cyst 55 31 hallmark (90%) Very frequent (99-80%) HP:0012062
22 neoplasm of the lung 55 31 frequent (33%) Frequent (79-30%) HP:0100526
23 benign neoplasm of the central nervous system 55 31 occasional (7.5%) Occasional (29-5%) HP:0100835
24 skin ulcer 55 31 occasional (7.5%) Occasional (29-5%) HP:0200042
25 abnormality of the face 55 Frequent (79-30%)
26 abnormality of the intestine 55 Frequent (79-30%)
27 fibroma 55 Very frequent (99-80%)
28 sarcoma 55 Very frequent (99-80%)

MGI Mouse Phenotypes related to Infantile Myofibromatosis:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.92 PDGFRB PTPRG CARMIL2 VIM DES MYH10
2 cardiovascular system MP:0005385 9.8 PDGFRB ACTC1 VIM DES MB MYH10
3 cellular MP:0005384 9.7 NOTCH3 PDGFRB ACTC1 VIM DES MB
4 homeostasis/metabolism MP:0005376 9.61 PDGFRB ACTC1 CARMIL2 VIM DES MB
5 muscle MP:0005369 9.17 PDGFRB ACTC1 VIM DES MB MYH10

Drugs & Therapeutics for Infantile Myofibromatosis

Search Clinical Trials , NIH Clinical Center for Infantile Myofibromatosis

Genetic Tests for Infantile Myofibromatosis

Genetic tests related to Infantile Myofibromatosis:

# Genetic test Affiliating Genes
1 Infantile Myofibromatosis 28

Anatomical Context for Infantile Myofibromatosis

MalaCards organs/tissues related to Infantile Myofibromatosis:

38
Bone, Skin, Lung, Smooth Muscle, Heart, Kidney, Eye

Publications for Infantile Myofibromatosis

Articles related to Infantile Myofibromatosis:

(show top 50) (show all 205)
# Title Authors Year
1
Infantile myofibromatosis - a clinical and pathological diagnostic challenge. ( 28541875 )
2017
2
"Exome sequencing identifies a novel homozygous variant in NDRG4 in a family with infantile myofibromatosis (Linhares etA al., 2014)" turns out to be EBV+ leiomyomatosis caused by CARMIL2 mutations. ( 28223207 )
2017
3
A Rare Case of Infantile Myofibromatosis Presenting to the Emergency Department as Undiagnosed Long Bone Fractures. ( 29095782 )
2017
4
Infantile myofibromatosis of the iliac bone. ( 29263742 )
2017
5
Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene. ( 28183292 )
2017
6
The spectrum of infantile myofibromatosis includes both non-penetrance and adult recurrence. ( 28286173 )
2017
7
PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis. ( 28334876 )
2017
8
Heterozygous PDGFRB Mutation in a Three-generation Family with Autosomal Dominant Infantile Myofibromatosis. ( 28417142 )
2017
9
Infantile myofibromatosis. ( 29364448 )
2017
10
Whole-body magnetic resonance imaging in the diagnosis and follow-up of multicentric infantile myofibromatosis: A case report. ( 28413672 )
2017
11
A large mediastinal tumour invading into the liver with foetal hydrops: A rare case of infantile myofibromatosis. ( 28395635 )
2017
12
Multiple Bone Lesions in an 8-Month-Old Child Presenting with Pathologic Fracture: A Rare Case of Solely Osseous Multicentric Infantile Myofibromatosis. ( 29252675 )
2016
13
A case of advanced infantile myofibromatosis harboring a novel MYH10-RET fusion. ( 28028925 )
2016
14
Extracalvarial Composite Infantile Myofibromatosis: Case Report and Literature Review. ( 28018804 )
2016
15
An unusual cause of neonatal hip dislocation: Infantile myofibromatosis presenting as developmental dysplasia of the hip. ( 27646511 )
2016
16
Intracranial Infantile Myofibromatosis Mimicking Malignant Brain Tumor: A Case Report and Literature Review. ( 27373934 )
2016
17
Six Cases of Myofibroma--The Adult Counterpart of Infantile Myofibromatosis: Case Report. ( 26718074 )
2016
18
CD34-positive infantile myofibromatosis: Case report and review of hemangiopericytoma-like pattern tumors. ( 27074874 )
2016
19
Infantile Myofibromatosis of the Soft Palate. ( 26080220 )
2015
20
Generalized infantile myofibromatosis with a monophasic primitive pattern. ( 25989870 )
2015
21
Kidney transplantation in infantile myofibromatosis and fibromuscular dysplasia: a case report. ( 26603035 )
2015
22
Spontaneous Regression of an Infantile Scalp Tumor. Infantile myofibromatosis. ( 25692278 )
2015
23
Infantile myofibromatosis of uterus: A case report. ( 26905167 )
2015
24
PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib. ( 26455322 )
2015
25
Vincristine and Dactinomycin in Infantile Myofibromatosis With a Review of Treatment Options. ( 25389917 )
2014
26
Infantile myofibromatosis as an unusual cause for unilateral atelectasis in an infant. ( 24453022 )
2014
27
Diagnosis of infantile myofibromatosis with pseudo-ulcerated plaque using prenatal ultrasound: A case report. ( 25371730 )
2014
28
Chemotherapy for Generalized Infantile Myofibromatosis With Visceral Involvement. ( 24608078 )
2014
29
Exome sequencing identifies a novel homozygous variant in NDRG4 in a family with infantile myofibromatosis. ( 25241110 )
2014
30
Infantile myofibromatosis: a series of 28 cases. ( 24894456 )
2014
31
Modulation of expressivity in PDGFRB-related infantile myofibromatosis: a role for PTPRG? ( 25158255 )
2014
32
Infantile myofibromatosis. Study of a case using whole body ultrasound and MRI. ( 22118778 )
2014
33
Prenatal diagnosis of infantile myofibromatosis of the lung: a case report and review of the literature. ( 23686518 )
2013
34
Mutations in PDGFRB and NOTCH3 are the first genetic causes identified for autosomal dominant infantile myofibromatosis. ( 23865785 )
2013
35
Congenital solitary infantile myofibromatosis involving the spinal cord. ( 23082913 )
2013
36
A recurrent PDGFRB mutation causes familial infantile myofibromatosis. ( 23731537 )
2013
37
Solitary infantile myofibromatosis in the bones of the upper extremities: Two rare cases and a review of the literature. ( 24179532 )
2013
38
Recurrent infantile myofibromatosis in a 19-month-old boy presenting as ulcerated plaque. ( 24517046 )
2013
39
Ulcerated congenital tumor. Solitary infantile myofibromatosis. ( 23375150 )
2013
40
Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. ( 23731542 )
2013
41
Infantile myofibromatosis: report on a family with autosomal dominant inheritance and variable penetrance. ( 23217896 )
2012
42
Risk-adapted therapy for infantile myofibromatosis in children. ( 22038698 )
2012
43
Isolated infantile myofibromatosis of the upper eyelid: uncommon localization and long-term results after surgical management. ( 22813815 )
2012
44
Multicentric infantile myofibromatosis of the small bowel detected by video capsule endoscopy in a child. ( 22814908 )
2012
45
Imaging findings in seven cases of congenital infantile myofibromatosis with cerebral, spinal, or head and neck involvement. ( 23223874 )
2012
46
Rapid spontaneous regression of multicentric infantile myofibromatosis in the posterior fossa and lumbar vertebra. ( 20949273 )
2011
47
Solitary infantile myofibromatosis of the cranial vault: case report. ( 21279363 )
2011
48
Spontaneous remission of solitary-type infantile myofibromatosis. ( 21941483 )
2011
49
Infantile myofibromatosis: two families supporting autosomal dominant inheritance. ( 21834820 )
2011
50
Stretched and sheared microcatheter retained after onyx embolization of infantile myofibromatosis. ( 21696669 )
2011

Variations for Infantile Myofibromatosis

ClinVar genetic disease variations for Infantile Myofibromatosis:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PDGFRB NM_002609.3(PDGFRB): c.1681C> T (p.Arg561Cys) single nucleotide variant Pathogenic rs367543286 GRCh37 Chromosome 5, 149505134: 149505134
2 PDGFRB NM_002609.3(PDGFRB): c.1978C> A (p.Pro660Thr) single nucleotide variant Pathogenic rs144050370 GRCh37 Chromosome 5, 149503858: 149503858
3 NOTCH3 NM_000435.2(NOTCH3): c.4556T> C (p.Leu1519Pro) single nucleotide variant Pathogenic rs367543285 GRCh37 Chromosome 19, 15285059: 15285059
4 PDGFRB NM_002609.3(PDGFRB): c.1998C> A (p.Asn666Lys) single nucleotide variant Pathogenic/Likely pathogenic rs864309711 GRCh38 Chromosome 5, 150124275: 150124275
5 PDGFRB NM_002609.3(PDGFRB): c.1699A> G (p.Lys567Glu) single nucleotide variant Pathogenic GRCh38 Chromosome 5, 150125553: 150125553
6 PDGFRB NM_002609.3(PDGFRB): c.1697_1702delGGAAGG (p.Trp566_Val568delinsLeu) deletion Pathogenic rs1060499543 GRCh38 Chromosome 5, 150125550: 150125555
7 PDGFRB NM_002609.3(PDGFRB): c.1998C> G (p.Asn666Lys) single nucleotide variant Pathogenic rs864309711 GRCh37 Chromosome 5, 149503838: 149503838
8 PDGFRB NM_002609.3(PDGFRB): c.1615_1616insGAT (p.Ile538_Leu539insArg) insertion Pathogenic rs1060499541 GRCh38 Chromosome 5, 150126578: 150126579
9 PDGFRB NM_002609.3(PDGFRB): c.2549A> T (p.Asp850Val) single nucleotide variant Pathogenic rs1060499540 GRCh37 Chromosome 5, 149500488: 149500488
10 PDGFRB NM_002609.3(PDGFRB): c.1696T> C (p.Trp566Arg) single nucleotide variant Pathogenic rs1060499542 GRCh38 Chromosome 5, 150125556: 150125556

Cosmic variations for Infantile Myofibromatosis:

9
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA Conf
1 COSM584 NRAS skin,neck,benign melanocytic nevus,congenital c.182A>G p.Q61R 7
2 COSM580 NRAS skin,hand,benign melanocytic nevus,congenital c.181C>A p.Q61K 6
3 COSM476 BRAF skin,trunk,benign melanocytic nevus,congenital c.1799T>A p.V600E 6
4 COSM28757 GNAQ skin,hand,benign melanocytic nevus,cellular c.626A>T p.Q209L 5

Expression for Infantile Myofibromatosis

Search GEO for disease gene expression data for Infantile Myofibromatosis.

Pathways for Infantile Myofibromatosis

Pathways related to Infantile Myofibromatosis according to KEGG:

36
# Name Kegg Source Accession
1 Notch signaling pathway hsa04330
2 PI3K-Akt signaling pathway hsa04151

Pathways related to Infantile Myofibromatosis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.97 NOTCH3 PDGFRB VIM
2 11.75 ACTC1 DES MYH10 VIM
3 11.28 NDRG4 NOTCH3 PDGFRB
4
Show member pathways
10.91 DES VIM
5 10.66 ACTC1 DES VIM

GO Terms for Infantile Myofibromatosis

Cellular components related to Infantile Myofibromatosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intermediate filament cytoskeleton GO:0045111 9.32 CARMIL2 DES
2 cell leading edge GO:0031252 9.26 CARMIL2 VIM
3 extracellular exosome GO:0070062 9.17 ACTC1 DES MB MYH10 PDGFRB PTPRG
4 polysome GO:0005844 9.16 MYH10 VIM
5 lamellipodium GO:0030027 9.13 ACTC1 CARMIL2 MYH10

Biological processes related to Infantile Myofibromatosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actomyosin structure organization GO:0031032 9.37 ACTC1 MYH10
2 positive regulation of collagen biosynthetic process GO:0032967 9.32 PDGFRB VIM
3 intermediate filament organization GO:0045109 9.26 DES VIM
4 actin filament-based movement GO:0030048 9.16 ACTC1 MYH10
5 cardiac myofibril assembly GO:0055003 8.96 ACTC1 PDGFRB
6 muscle filament sliding GO:0030049 8.8 ACTC1 DES VIM

Sources for Infantile Myofibromatosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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