Feingold syndrome type 1
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Also known as Brunner-Winter syndrome type 1digital anomalies with short palpebral fissures and atresia of esophagus or duodenum type 1digital anomalies with short palpebral fissures and atresia of oesophagus or duodenumdigital anomalies with short palpebral fissures and atresia of oesophagus or duodenum type 1Feingold syndrome 1Feingold syndrome caused by mutation in MYCNFGLDS1FS1microcephaly, mental retardation, and tracheoesophageal fistula syndromemicrocephaly-digital anomalies-normal intelligence syndrome type 1microcephaly-intellectual disability-tracheoesophageal fistula syndrome type 1microcephaly-oculo-digito-esophageal-duodenal syndrome syndrome type 1MMT type 1MODED syndrome type 1MYCN Feingold syndromeoculo-digito-esophageal-duodenal syndrome type 1ODED syndrome type 1
Summary
Feingold syndrome type 1 (MONDO:0008115) is a disease caused by MYCN (GenCC Definitive), with 3 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: MYCN (GenCC Definitive)
- Cohort genes: 3
- ClinVar variants: 123
- Phenotypes (HPO): 35
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 120 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Signs & symptoms
Clinical features (HPO)
35 HPO clinical features (Orphanet curated; top 35 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000252 | Microcephaly | Very frequent (80-99%) |
| HP:0001770 | Toe syndactyly | Very frequent (80-99%) |
| HP:0002589 | Gastrointestinal atresia | Very frequent (80-99%) |
| HP:0005819 | Short middle phalanx of finger | Very frequent (80-99%) |
| HP:0000347 | Micrognathia | Frequent (30-79%) |
| HP:0001328 | Specific learning disability | Frequent (30-79%) |
| HP:0001999 | Abnormal facial shape | Frequent (30-79%) |
| HP:0002032 | Esophageal atresia | Frequent (30-79%) |
| HP:0004209 | Clinodactyly of the 5th finger | Frequent (30-79%) |
| HP:0004220 | Short middle phalanx of the 5th finger | Frequent (30-79%) |
| HP:0004691 | 2-3 toe syndactyly | Frequent (30-79%) |
| HP:0004692 | 4-5 toe syndactyly | Frequent (30-79%) |
| HP:0009577 | Short middle phalanx of the 2nd finger | Frequent (30-79%) |
| HP:0009778 | Short thumb | Frequent (30-79%) |
| HP:0012745 | Short palpebral fissure | Frequent (30-79%) |
| HP:0000076 | Vesicoureteral reflux | Occasional (5-29%) |
| HP:0000077 | Abnormality of the kidney | Occasional (5-29%) |
| HP:0000083 | Renal insufficiency | Occasional (5-29%) |
| HP:0000085 | Horseshoe kidney | Occasional (5-29%) |
| HP:0000110 | Renal dysplasia | Occasional (5-29%) |
| HP:0000123 | Nephritis | Occasional (5-29%) |
| HP:0000126 | Hydronephrosis | Occasional (5-29%) |
| HP:0000405 | Conductive hearing impairment | Occasional (5-29%) |
| HP:0000407 | Sensorineural hearing impairment | Occasional (5-29%) |
| HP:0001627 | Abnormal heart morphology | Occasional (5-29%) |
| HP:0001643 | Patent ductus arteriosus | Occasional (5-29%) |
| HP:0002247 | Duodenal atresia | Occasional (5-29%) |
| HP:0010446 | Tricuspid stenosis | Occasional (5-29%) |
| HP:0011611 | Interrupted aortic arch | Occasional (5-29%) |
| HP:0011625 | Multiple muscular ventricular septal defects | Occasional (5-29%) |
| HP:0011662 | Tricuspid atresia | Occasional (5-29%) |
| HP:0001249 | Intellectual disability | Very rare (<1-4%) |
| HP:0002023 | Anal atresia | Very rare (<1-4%) |
| HP:0004322 | Short stature | Very rare (<1-4%) |
| HP:0005235 | Jejunal atresia | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Feingold syndrome type 1 |
| Mondo ID | MONDO:0008115 |
| OMIM | 164280 |
| Orphanet | 391641 |
| SNOMED CT | 702431004 |
| UMLS | C4551774 |
| MedGen | 1637716 |
| GARD | 0017624 |
| Is cancer (heuristic) | no |
Also known as: Brunner-Winter syndrome type 1 · digital anomalies with short palpebral fissures and atresia of esophagus or duodenum type 1 · digital anomalies with short palpebral fissures and atresia of oesophagus or duodenum · digital anomalies with short palpebral fissures and atresia of oesophagus or duodenum type 1 · Feingold syndrome 1 · Feingold syndrome caused by mutation in MYCN · Feingold syndrome type 1 · FGLDS1 · FS1 · microcephaly, mental retardation, and tracheoesophageal fistula syndrome · microcephaly-digital anomalies-normal intelligence syndrome type 1 · microcephaly-intellectual disability-tracheoesophageal fistula syndrome type 1 · microcephaly-oculo-digito-esophageal-duodenal syndrome syndrome type 1 · MMT type 1 · MODED syndrome type 1 · MYCN Feingold syndrome · oculo-digito-esophageal-duodenal syndrome type 1 · ODED syndrome type 1
Data availability: 123 ClinVar variants · 5 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Feingold syndrome › Feingold syndrome type 1
Related subtypes (1): Feingold syndrome type 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
123 retrieved; paginated sample, class counts are floors:
64 uncertain significance, 18 pathogenic, 14 likely pathogenic, 11 conflicting classifications of pathogenicity, 8 likely benign, 5 pathogenic/likely pathogenic, 2 not provided, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1323303 | NM_005378.6(MYCN):c.559del (p.Val187fs) | MYCN | Pathogenic | criteria provided, single submitter |
| 13892 | NM_005378.6(MYCN):c.1178G>A (p.Arg393His) | MYCN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13893 | NM_005378.6(MYCN):c.1177C>A (p.Arg393Ser) | MYCN | Pathogenic | no assertion criteria provided |
| 13894 | NM_005378.6(MYCN):c.1181G>A (p.Arg394His) | MYCN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13896 | NM_005378.6(MYCN):c.217G>T (p.Glu73Ter) | MYCN | Pathogenic | no assertion criteria provided |
| 13897 | NM_005378.6(MYCN):c.626dup (p.Ala210fs) | MYCN | Pathogenic | criteria provided, single submitter |
| 1709269 | NM_005378.6(MYCN):c.256G>T (p.Glu86Ter) | MYCN | Pathogenic | criteria provided, single submitter |
| 1710469 | NM_005378.6(MYCN):c.403C>T (p.Gln135Ter) | MYCN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2108584 | NM_005378.6(MYCN):c.621dup (p.Ala208fs) | MYCN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2507183 | NM_005378.6(MYCN):c.134del (p.Pro45fs) | MYCN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3376293 | NM_005378.6(MYCN):c.833_846del (p.Asp278fs) | MYCN | Pathogenic | criteria provided, single submitter |
| 433149 | NM_005378.6(MYCN):c.1014C>A (p.Tyr338Ter) | MYCN | Pathogenic | criteria provided, single submitter |
| 433150 | NM_005378.6(MYCN):c.68_71dup (p.Gln25fs) | MYCN | Pathogenic | criteria provided, single submitter |
| 433151 | NM_005378.6(MYCN):c.964C>T (p.Arg322Ter) | MYCN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 433152 | NM_005378.6(MYCN):c.1061dup (p.Ser355fs) | MYCN | Pathogenic | criteria provided, single submitter |
| 433154 | NM_005378.6(MYCN):c.902_903del (p.Val301fs) | MYCN | Pathogenic | criteria provided, single submitter |
| 4526864 | NM_005378.6(MYCN):c.985C>T (p.Gln329Ter) | MYCN | Pathogenic | criteria provided, single submitter |
| 4796616 | NM_005378.6(MYCN):c.411_417delinsTTCCA (p.Arg138fs) | MYCN | Pathogenic | criteria provided, single submitter |
| 545970 | NM_005378.6(MYCN):c.1117C>T (p.Arg373Ter) | MYCN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 817596 | NM_005378.6(MYCN):c.134dup (p.Glu47fs) | MYCN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13895 | NM_005378.6(MYCN):c.231G>A (p.Trp77Ter) | MYCNOS | Pathogenic | no assertion criteria provided |
| 2571637 | NM_005378.6(MYCN):c.367del (p.Arg123fs) | MYCNOS | Pathogenic | criteria provided, single submitter |
| 180573 | NM_001267550.2(TTN):c.67495C>T (p.Arg22499Ter) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1185065 | NM_005378.6(MYCN):c.796G>T (p.Glu266Ter) | MYCN | Likely pathogenic | no assertion criteria provided |
| 1285553 | NM_005378.6(MYCN):c.152del (p.Lys51fs) | MYCN | Likely pathogenic | criteria provided, single submitter |
| 1679249 | NM_005378.6(MYCN):c.77C>T (p.Pro26Leu) | MYCN | Likely pathogenic | criteria provided, single submitter |
| 2499579 | NM_005378.6(MYCN):c.1274_1283del (p.Lys425fs) | MYCN | Likely pathogenic | criteria provided, single submitter |
| 2506946 | NM_005378.6(MYCN):c.1211T>G (p.Leu404Arg) | MYCN | Likely pathogenic | criteria provided, single submitter |
| 2581158 | NM_005378.6(MYCN):c.633_634dup (p.Ala212fs) | MYCN | Likely pathogenic | criteria provided, single submitter |
| 2627009 | NM_005378.6(MYCN):c.727C>T (p.Gln243Ter) | MYCN | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · Orphanet: 4 · 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 |
|---|---|---|---|---|
| MYCN | Definitive | Autosomal dominant | Feingold syndrome type 1 | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MYCN | Orphanet:357027 | Hereditary retinoblastoma |
| MYCN | Orphanet:357034 | Non-hereditary retinoblastoma |
| MYCN | Orphanet:391641 | Feingold syndrome type 1 |
| MYCN | Orphanet:635 | Neuroblastoma |
Cohort genes → proteins
3 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| MYCN | HGNC:7559 | ENSG00000134323 | P04198 | N-myc proto-oncogene protein | gencc,clinvar |
| MYCNOS | HGNC:16911 | ENSG00000233718 | P40205 | N-cym protein | clinvar |
| TTN-AS1 | HGNC:44124 | ENSG00000237298 | TTN antisense RNA 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MYCN | N-myc proto-oncogene protein | Positively regulates the transcription of MYCNOS in neuroblastoma cells. |
| MYCNOS | N-cym protein | Regulates stability of MYCN in neuroblastoma cells by inhibiting GSK3B-mediated MYCN phosphorylation. |
Protein-family classification
Druggable: 0 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.0
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 |
|---|---|---|---|
| Transcription factor | 1 | 2.8× | 0.587 |
| Other/Unknown | 2 | 1.2× | 0.587 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| MYCN | Transcription factor | no | Tscrpt_reg_Myc, bHLH_dom, Tscrpt_reg_Myc_N | |
| MYCNOS | Other/Unknown | no | ||
| TTN-AS1 | Other/Unknown | no |
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) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cortical plate | 2 |
| ventricular zone | 2 |
| embryo | 1 |
| primordial germ cell in gonad | 1 |
| gastrocnemius | 1 |
| hindlimb stylopod muscle | 1 |
| right atrium auricular region | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MYCN | 223 | broad | yes | ventricular zone, cortical plate, embryo |
| MYCNOS | 153 | tissue_specific | marker | primordial germ cell in gonad, cortical plate, ventricular zone |
| TTN-AS1 | 174 | ubiquitous | marker | hindlimb stylopod muscle, gastrocnemius, right atrium auricular region |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MYCN | 7,345 |
| MYCNOS | 0 |
| TTN-AS1 | 0 |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| MYCN | P04198 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| MYCNOS | P40205 | 48.22 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Regulation of CDH1 mRNA translation by microRNAs | 1 | 1038.2× | 0.005 | MYCN |
| Signaling by ALK | 1 | 571.0× | 0.005 | MYCN |
| TGFBR3 expression | 1 | 456.8× | 0.005 | MYCN |
| Signaling by TGFBR3 | 1 | 368.4× | 0.005 | MYCN |
| Signaling by TGFB family members | 1 | 115.3× | 0.012 | MYCN |
| Regulation of PD-L1(CD274) transcription | 1 | 108.8× | 0.012 | MYCN |
| Signaling by Receptor Tyrosine Kinases | 1 | 51.7× | 0.022 | MYCN |
| Signal Transduction | 1 | 10.2× | 0.098 | MYCN |
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 |
|---|---|---|---|---|
| regulation of inner ear auditory receptor cell differentiation | 1 | 2808.7× | 0.006 | MYCN |
| negative regulation of kinase activity | 1 | 2106.5× | 0.006 | MYCNOS |
| autosome genomic imprinting | 1 | 1203.7× | 0.007 | MYCN |
| negative regulation of astrocyte differentiation | 1 | 766.0× | 0.008 | MYCN |
| positive regulation of programmed cell death | 1 | 561.7× | 0.008 | MYCN |
| negative regulation of reactive oxygen species metabolic process | 1 | 468.1× | 0.008 | MYCN |
| cartilage condensation | 1 | 383.0× | 0.008 | MYCN |
| astrocyte differentiation | 1 | 383.0× | 0.008 | MYCN |
| branching morphogenesis of an epithelial tube | 1 | 366.4× | 0.008 | MYCN |
| positive regulation of mesenchymal cell proliferation | 1 | 300.9× | 0.008 | MYCN |
| embryonic skeletal system morphogenesis | 1 | 195.9× | 0.012 | MYCN |
| epithelial cell proliferation | 1 | 156.0× | 0.012 | MYCN |
| embryonic digit morphogenesis | 1 | 150.5× | 0.012 | MYCN |
| positive regulation of miRNA transcription | 1 | 145.3× | 0.012 | MYCN |
| positive regulation of epithelial cell proliferation | 1 | 122.1× | 0.014 | MYCN |
| lung development | 1 | 99.1× | 0.016 | MYCN |
| regulation of protein stability | 1 | 62.9× | 0.023 | MYCNOS |
| negative regulation of gene expression | 1 | 34.5× | 0.039 | MYCN |
| protein stabilization | 1 | 33.4× | 0.039 | MYCNOS |
| positive regulation of cell migration | 1 | 30.9× | 0.040 | MYCNOS |
| positive regulation of gene expression | 1 | 19.4× | 0.061 | MYCN |
| negative regulation of apoptotic process | 1 | 17.4× | 0.064 | MYCNOS |
| positive regulation of DNA-templated transcription | 1 | 14.0× | 0.076 | MYCN |
| positive regulation of transcription by RNA polymerase II | 1 | 7.4× | 0.135 | MYCN |
| regulation of transcription by RNA polymerase II | 1 | 5.8× | 0.164 | MYCN |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3
Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MYCN | 0 | 0 |
| MYCNOS | 0 | 0 |
| TTN-AS1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| MYCN | 11 | Binding:11 |
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
0 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.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 3 | MYCN, MYCNOS, TTN-AS1 |
Undrugged target profiles
3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| MYCN | 11 | — |
| MYCNOS | 0 | — |
| TTN-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.