Infantile myofibromatosis

Summary

Infantile myofibromatosis (MONDO:0016824) is a disease with 2 cohort genes and 1 clinical trial. Top therapeutic interventions include selpercatinib.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 465
• Phenotypes (HPO): 28
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.67	Europe	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0001482	Subcutaneous nodule	Very frequent (80-99%)
HP:0003011	Abnormality of the musculature	Very frequent (80-99%)
HP:0008069	Neoplasm of the skin	Very frequent (80-99%)
HP:0010614	Fibroma	Very frequent (80-99%)
HP:0012062	Bone cyst	Very frequent (80-99%)
HP:0100242	Sarcoma	Very frequent (80-99%)
HP:0000169	Gingival fibromatosis	Frequent (30-79%)
HP:0000271	Abnormality of the face	Frequent (30-79%)
HP:0000765	Abnormal thorax morphology	Frequent (30-79%)
HP:0000929	Abnormal skull morphology	Frequent (30-79%)
HP:0000934	Chondrocalcinosis	Frequent (30-79%)
HP:0001595	Abnormality of the hair	Frequent (30-79%)
HP:0002242	Abnormal intestine morphology	Frequent (30-79%)
HP:0100526	Neoplasm of the lung	Frequent (30-79%)
HP:0000077	Abnormality of the kidney	Occasional (5-29%)
HP:0000478	Abnormality of the eye	Occasional (5-29%)
HP:0001376	Limitation of joint mobility	Occasional (5-29%)
HP:0002575	Tracheoesophageal fistula	Occasional (5-29%)
HP:0002797	Osteolysis	Occasional (5-29%)
HP:0002894	Neoplasm of the pancreas	Occasional (5-29%)
HP:0003072	Hypercalcemia	Occasional (5-29%)
HP:0004374	Hemiplegia/hemiparesis	Occasional (5-29%)
HP:0005107	Abnormal sacrum morphology	Occasional (5-29%)
HP:0005214	Intestinal obstruction	Occasional (5-29%)
HP:0007400	Irregular hyperpigmentation	Occasional (5-29%)
HP:0100835	Benign neoplasm of the central nervous system	Occasional (5-29%)
HP:0200042	Skin ulcer	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	infantile myofibromatosis
Mondo ID	MONDO:0016824
MeSH	D018224
OMIM	228550
Orphanet	2591
DOID	DOID:0080109
NCIT	C3742
UMLS	C0432284
MedGen	140933
GARD	0002998
NORD	1301
Is cancer (heuristic)	no

Also known as: IMS · infantile hemangiopericytoma · infantile myofibromatosis · multicentric myofibromatosis · myofibromatosis

Data availability: 465 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › mesenchymal cell neoplasm › pericytic neoplasm › benign perivascular tumor › infantile myofibromatosis

Related subtypes (3): glomangiomatosis, myofibroma, angioleiomyoma

Subtypes (2): myofibromatosis, infantile, 1, myofibromatosis, infantile, 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

465 retrieved; paginated sample, class counts are floors:

202 likely benign, 123 uncertain significance, 58 benign, 41 conflicting classifications of pathogenicity, 25 benign/likely benign, 12 pathogenic, 3 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
208692	NM_002609.4(PDGFRB):c.1996A>C (p.Asn666His)	PDGFRB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2096300	NM_002609.4(PDGFRB):c.2483C>A (p.Ala828Glu)	PDGFRB	Pathogenic	criteria provided, single submitter
218935	NM_002609.4(PDGFRB):c.1998C>A (p.Asn666Lys)	PDGFRB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2925384	NM_002609.4(PDGFRB):c.1679C>T (p.Pro560Leu)	PDGFRB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375555	NM_002609.4(PDGFRB):c.1697_1702del (p.Trp566_Val568delinsLeu)	PDGFRB	Pathogenic	no assertion criteria provided
375556	NM_002609.4(PDGFRB):c.1998C>G (p.Asn666Lys)	PDGFRB	Pathogenic	criteria provided, single submitter
375557	NM_002609.4(PDGFRB):c.1615_1616insGAT (p.Ile538_Leu539insArg)	PDGFRB	Pathogenic	no assertion criteria provided
375681	NM_002609.4(PDGFRB):c.2549A>T (p.Asp850Val)	PDGFRB	Pathogenic	criteria provided, single submitter
375682	NM_002609.4(PDGFRB):c.1696T>C (p.Trp566Arg)	PDGFRB	Pathogenic	criteria provided, multiple submitters, no conflicts
55848	NM_002609.4(PDGFRB):c.1681C>T (p.Arg561Cys)	PDGFRB	Pathogenic	criteria provided, multiple submitters, no conflicts
973194	NM_002609.4(PDGFRB):c.1519_1520insTACTGTCGGTGC (p.Val506_Arg507insLeuLeuSerVal)	PDGFRB	Pathogenic	criteria provided, single submitter
973195	NM_002609.4(PDGFRB):c.1716_1717insGAGCTGATCCGATGGAAGGTGATTGAGTCTGTG (p.Val572_Ser573insGluLeuIleArgTrpLysValIleGluSerVal)	PDGFRB	Pathogenic	criteria provided, single submitter
973196	NM_002609.4(PDGFRB):c.1682_1684del (p.Arg561_Tyr562delinsHis)	PDGFRB	Pathogenic	criteria provided, single submitter
973197	NM_002609.4(PDGFRB):c.1684T>G (p.Tyr562Asp)	PDGFRB	Pathogenic	criteria provided, single submitter
973198	NM_002609.4(PDGFRB):c.1613T>A (p.Ile538Asn)	PDGFRB	Pathogenic	criteria provided, single submitter
4794434	NM_002609.4(PDGFRB):c.1A>G (p.Met1Val)	PDGFRB	Likely pathogenic	criteria provided, single submitter
1304805	NM_002609.4(PDGFRB):c.419C>T (p.Thr140Met)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135650	NM_002609.4(PDGFRB):c.2083C>T (p.Arg695Cys)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1486244	NM_002609.4(PDGFRB):c.2905-8G>A	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1518353	NM_002609.4(PDGFRB):c.1526C>T (p.Thr509Met)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194497	NM_002609.4(PDGFRB):c.2126G>A (p.Arg709His)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1946074	NM_002609.4(PDGFRB):c.938G>A (p.Ser313Asn)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1960043	NM_002609.4(PDGFRB):c.2164G>A (p.Val722Ile)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1961685	NM_002609.4(PDGFRB):c.2122C>T (p.Arg708Cys)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1975317	NM_002609.4(PDGFRB):c.3275C>T (p.Ser1092Leu)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2042019	NM_002609.4(PDGFRB):c.1535A>G (p.Asn512Ser)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2054278	NM_002609.4(PDGFRB):c.338G>A (p.Arg113Gln)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2056802	NM_002609.4(PDGFRB):c.3181G>A (p.Asp1061Asn)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2065779	NM_002609.4(PDGFRB):c.2971C>T (p.Arg991Cys)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2144767	NM_002609.4(PDGFRB):c.542G>C (p.Gly181Ala)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 26 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PDGFRB	Strong	Autosomal dominant	myofibromatosis, infantile, 1	17
NOTCH3	Supportive	Autosomal dominant	infantile myofibromatosis	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDGFRB	Orphanet:168950	Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement
PDGFRB	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFRB	Orphanet:2591	Infantile myofibromatosis
PDGFRB	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRB	Orphanet:363665	Acroosteolysis-keloid-like lesions-premature aging syndrome
PDGFRB	Orphanet:477831	Kosaki overgrowth syndrome
PDGFRB	Orphanet:86830	Chronic myeloproliferative disease, unclassifiable
NOTCH3	Orphanet:136	Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy
NOTCH3	Orphanet:2591	Infantile myofibromatosis
NOTCH3	Orphanet:2789	Lateral meningocele syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PDGFRB	HGNC:8804	ENSG00000113721	P09619	Platelet-derived growth factor receptor beta	gencc,clinvar
NOTCH3	HGNC:7883	ENSG00000074181	Q9UM47	Neurogenic locus notch homolog protein 3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDGFRB	Platelet-derived growth factor receptor beta	Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, surviv…
NOTCH3	Neurogenic locus notch homolog protein 3	Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.112
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDGFRB	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
NOTCH3	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right coronary artery	2
endocervix	1
stromal cell of endometrium	1
popliteal artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDGFRB	270	ubiquitous	marker	stromal cell of endometrium, right coronary artery, endocervix
NOTCH3	273	ubiquitous	marker	popliteal artery, tibial artery, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFRB	5,111
NOTCH3	4,403

Intra-cohort edges

A	B	Sources
NOTCH3	PDGFRB	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDGFRB	P09619	8
NOTCH3	Q9UM47	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective LFNG causes SCDO3	1	1142.0×	0.007	NOTCH3
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	951.7×	0.007	NOTCH3
Noncanonical activation of NOTCH3	1	713.8×	0.007	NOTCH3
Pre-NOTCH Processing in Golgi	1	317.2×	0.009	NOTCH3
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	237.9×	0.009	NOTCH3
NOTCH3 Intracellular Domain Regulates Transcription	1	219.6×	0.009	NOTCH3
Notch-HLH transcription pathway	1	203.9×	0.009	NOTCH3
Downstream signal transduction	1	190.3×	0.009	PDGFRB
Signaling by PDGF	1	126.9×	0.012	PDGFRB
Constitutive Signaling by Aberrant PI3K in Cancer	1	63.4×	0.021	PDGFRB
Pre-NOTCH Transcription and Translation	1	61.4×	0.021	NOTCH3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.024	PDGFRB
PIP3 activates AKT signaling	1	33.4×	0.032	PDGFRB
RAF/MAP kinase cascade	1	30.5×	0.032	PDGFRB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of smooth muscle cell proliferation	2	330.4×	4e-04	PDGFRB, NOTCH3
cell migration involved in coronary angiogenesis	1	8426.0×	0.002	PDGFRB
metanephric glomerular mesangial cell proliferation involved in metanephros development	1	8426.0×	0.002	PDGFRB
cell migration involved in vasculogenesis	1	4213.0×	0.002	PDGFRB
smooth muscle cell chemotaxis	1	4213.0×	0.002	PDGFRB
positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway	1	2808.7×	0.002	PDGFRB
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	2808.7×	0.002	PDGFRB
glomerular capillary formation	1	2808.7×	0.002	NOTCH3
metanephric glomerular capillary formation	1	2808.7×	0.002	PDGFRB
smooth muscle adaptation	1	2106.5×	0.002	PDGFRB
platelet-derived growth factor receptor-beta signaling pathway	1	1685.2×	0.002	PDGFRB
neuroblast differentiation	1	1053.2×	0.003	NOTCH3
retina vasculature development in camera-type eye	1	842.6×	0.004	PDGFRB
cardiac myofibril assembly	1	648.1×	0.005	PDGFRB
positive regulation of DNA biosynthetic process	1	561.7×	0.005	PDGFRB
positive regulation of smooth muscle cell migration	1	495.6×	0.005	PDGFRB
positive regulation of calcium ion import	1	468.1×	0.005	PDGFRB
aorta morphogenesis	1	443.5×	0.005	PDGFRB
positive regulation of chemotaxis	1	421.3×	0.005	PDGFRB
neuron fate commitment	1	401.2×	0.005	NOTCH3
artery morphogenesis	1	337.0×	0.006	NOTCH3
positive regulation of MAP kinase activity	1	324.1×	0.006	PDGFRB
platelet-derived growth factor receptor signaling pathway	1	280.9×	0.007	PDGFRB
positive regulation of mitotic nuclear division	1	271.8×	0.007	PDGFRB
positive regulation of reactive oxygen species metabolic process	1	255.3×	0.007	PDGFRB
peptidyl-tyrosine phosphorylation	1	210.7×	0.008	PDGFRB
positive regulation of calcium-mediated signaling	1	210.7×	0.008	PDGFRB
forebrain development	1	175.5×	0.009	NOTCH3
positive regulation of miRNA transcription	1	145.3×	0.010	NOTCH3
negative regulation of neuron differentiation	1	135.9×	0.011	NOTCH3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PDGFRB	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRB	102	4
NOTCH3	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	PDGFRB
FEDRATINIB	4	PDGFRB
TIVOZANIB	4	PDGFRB
LENVATINIB	4	PDGFRB
AXITINIB	4	PDGFRB
SORAFENIB	4	PDGFRB
SUNITINIB MALATE	4	PDGFRB
REGORAFENIB	4	PDGFRB
PACRITINIB	4	PDGFRB
VANDETANIB	4	PDGFRB
NILOTINIB	4	PDGFRB
BOSUTINIB	4	PDGFRB
NINTEDANIB ESYLATE	4	PDGFRB
GILTERITINIB	4	PDGFRB
TOVORAFENIB	4	PDGFRB
PEXIDARTINIB	4	PDGFRB
PAZOPANIB	4	PDGFRB
NINTEDANIB	4	PDGFRB
SUNITINIB	4	PDGFRB
DASATINIB	4	PDGFRB
ERLOTINIB	4	PDGFRB
LAPATINIB	4	PDGFRB
QUIZARTINIB	4	PDGFRB
MIDOSTAURIN	4	PDGFRB
IMATINIB	4	PDGFRB
VATALANIB	3	PDGFRB
FAMITINIB	3	PDGFRB
MASITINIB	3	PDGFRB
CRENOLANIB	3	PDGFRB
SARACATINIB	3	PDGFRB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PDGFRB	1,237	Binding:1213, Functional:16, ADMET:8
NOTCH3	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PDGFRB	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PDGFRB	1,237

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	PDGFRB
FEDRATINIB	4	PDGFRB
TIVOZANIB	4	PDGFRB
LENVATINIB	4	PDGFRB
AXITINIB	4	PDGFRB
SORAFENIB	4	PDGFRB
SUNITINIB MALATE	4	PDGFRB
REGORAFENIB	4	PDGFRB
PACRITINIB	4	PDGFRB
VANDETANIB	4	PDGFRB
NILOTINIB	4	PDGFRB
BOSUTINIB	4	PDGFRB
NINTEDANIB ESYLATE	4	PDGFRB
GILTERITINIB	4	PDGFRB
TOVORAFENIB	4	PDGFRB
PEXIDARTINIB	4	PDGFRB
PAZOPANIB	4	PDGFRB
NINTEDANIB	4	PDGFRB
SUNITINIB	4	PDGFRB
DASATINIB	4	PDGFRB
ERLOTINIB	4	PDGFRB
LAPATINIB	4	PDGFRB
QUIZARTINIB	4	PDGFRB
MIDOSTAURIN	4	PDGFRB
IMATINIB	4	PDGFRB
VATALANIB	3	PDGFRB
FAMITINIB	3	PDGFRB
MASITINIB	3	PDGFRB
CRENOLANIB	3	PDGFRB
SARACATINIB	3	PDGFRB

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDGFRB
B	Phased (≥1) drug, not yet approved	1	NOTCH3
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03899792	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SELPERCATINIB	4	1
CHEMBL5430810	0	1