DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Feingold syndrome — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFeingold syndrome maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for feingold syndrome is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
MYCN proto-oncogene, bHLH transcription factor (MYCN) — MYCN is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5G1X · 1.72 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Feingold syndrome is a dominantly inherited combination of hand and foot abnormalities, microcephaly, oesophageal or duodenal atresia, short palpebral fissures and learning disabilities. In a review of seven families, intestinal atresia or obstruction occurred in approximately one third of patients. A later review of at least 79 patients in 25 families gave the following frequencies: hand anomalies in all patients, foot anomalies in 80%, microcephaly in 87%, gastrointestinal atresia in 38%, heart anomaly in 14%, deafness in 7% and renal involvement in 5%. Imperforate anus has been reported in a father and daughter with the syndrome; the father had a recto-vesical fistula, and the infant had long-gap oesophageal atresia without fistula. One case of Feingold syndrome with a ring chromosome 13 has been described, in a neonate who also had duodenal and anal atresia, cleft palate, absent thumbs, and cardiac defects including PDA, VSD and persistent foramen ovale.
The causative gene for Feingold syndrome is MYCN on chromosome 2p24.1. A nonsense mutation, c.217G>T (p.Glu73X), was identified in a boy with classical features including oesophageal atresia, microcephaly, clinodactyly, and a developmental quotient of 59 at age 4. His mother and maternal grandmother carried the same mutation but had only microcephaly, fifth finger clinodactyly, partial toe syndactyly, and normal intelligence — a presentation previously labelled as "microcephaly-digital abnormalities-normal intelligence" syndrome. This supports the view that the latter is a mild form of Feingold syndrome. No MYCN mutations were detected in patients with VATER association or non-syndromic oesophageal atresia.
What is still missing is a systematic understanding of the full pathogenic spectrum of MYCN defects, including why the same mutation produces such variable expressivity even within a single family. No drug or treatment is mentioned in any of these abstracts; the work is entirely genetic and descriptive. Larger, prospectively collected cohorts with standardised phenotyping and long-term follow-up would be needed to clarify the natural history and to identify any modifiable factors. No clinical trial data exist.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics · 1997 · 27 citations
Feingold syndrome: Report of a new family and review
AbstractFeingold syndrome (or oculodigitoesophagoduodenal syndrome; Microcephaly, Mesobrachyphalangy, Tracheo-esophageal fistula syndrome) is a dominantly inherited combination of hand and foot abnormalities, microcephaly, esophageal/duodenal atresia, short palpebral fissures and learning disabilities, first reported in 1975 (MIM 164280). We report on the seventh family with Feingold syndrome. The propositus is a male infant with esophageal and duodenal atresia, brachymesophalangy of the fifth fingers, bilateral syndactyly of toes 4-5 (and 2-3), relative microcephaly, and facial anomalies. His mother also has microcephaly, similar facial appearance, short fifth fingers with single flexion crease, syndactyly of toes 4-5, and learning disabilities. The maternal sister, brother, and grandmother of the propositus have the same phenotype. The 7 families with Feingold syndrome are reviewed. Intestinal (esophageal/duodenal) atresia/obstruction occurs in approximately 1/3 of the patients with Feingold syndrome.
American Journal of Medical Genetics Part A · 2006 · 23 citations
Expanding the clinical spectrum of <i>MYCN</i>‐related Feingold syndrome
AbstractFeingold syndrome (OMIM#164280) is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disability/mental retardation. Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges [Feingold et al., 1997]. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients [Kellermayer et al., 2005]. As a result of the versatile clinical picture, this entity has also been reported as oculo-duodeno-esophageal-digital (ODED) syndrome, microcephaly-oculo-digito-esophageal-duodenal syndrome, and microcephaly-mesobrachyphalangy-tracheoesophageal-fistula (MMT) syndrome. However, some of the variable features of Feingold syndrome are included in “microcephaly-digital abnormalities-normal intelligence” (MIM#602585), described as an independent, distinct condition [Kawame et al., 1997]. The critical region of Feingold syndrome was mapped to chromosome 2p23-p24 [Celli et al., 2003] and a recent article revealed MYCN (2p24.1), as a causative gene in this genetic entity [van Bokhoven et al., 2005]. These findings indicated that MYCN dosage is an important factor in early embryonic development and postnatal brain growth. Indeed, studies in human fetal brain and mice suggest that MYCN is involved in embryonic limb, visceral organ, and nervous system development [Hirvonen et al., 1990; Moens et al., 1992; Stanton et al., 1992]. Here, we report on a family—expressing variable features of Feingold syndrome—who carry a novel mutation of MYCN. The boy with classical features of the syndrome and his mother and maternal grandmother, only possessing the clinical phenotype of “microcephaly-digital abnormalities-normal intelligence” disorder also carry the same pathogenic mutation. The 4-year-old boy was born as a first child from non-consanguineous parents. The pregnancy was complicated by maternal nephropathy. He was delivered vaginally at 39 weeks with Apgars 4 and 8 at 1 and 5 min, birth weight 3,300 g. Esophageal atresia (Vogt III/B type) was detected shortly after birth and was repaired surgically. Cranial ultrasound showed subependymal hemorrhage. He developed seizures and has been treated with anti-epileptics since the age of 10 months. At the age of 4 he could not walk independently and his developmental quotient was 59 (Budapest-Binet). On physical examination his length was 98 cm (10–25 pc), weight 13.5 kg (5 pc), and OFC 46 cm (<−2 SD). Microcephaly and scaphocephaly, epicanthal folds, down-slanting palpebral fissures, relatively large ears, bulbous nasal tip, and dental malocclusion could be observed (Fig. 1). He also had clinodactyly of the fifth finger of the hands, small distal phalanges of the thumbs, mild brachydactyly on the feet, contractures of the wrist, elbow, ankle, and knee, and increased muscle tone. Bullet-shaped distal phalanges of the first finger, middle phalanx hypoplasia of the fifth finger, and absent middle phalanges of the fourth and fifth toes were verified by X-ray. Karyotype analysis was normal (46,XY) and the diagnosis of Feingold syndrome was entertained. Sequence analysis of the MYCN gene [van Bokhoven et al., 2005] revealed a nonsense mutation c.217G > T (p.Glu73X) in exon 2. Clinical pictures of the affected family members. A: The proband. B: The mother. C: The maternal grandmother. Note the common features of microcephaly, fifth finger clinodactyly, and mild brachy-syndactyly (most prominent in the mother) of the toes. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] The mother and the maternal grandmother of the patient were also microcephalic with OFC 49.5 cm (<−2 SD) for the mother and OFC 52 cm (<−2 SD) for the grandmother. Fifth finger clinodactyly and partial syndactyly of second to third and fourth to fifth toes could be observed on them (Fig. 1). The mother had a spontaneous abortion from an earlier relationship. She suffered from chronic nephritis syndrome, renal insufficiency, and hypertension. Her IQ was 97 according to MAWI. The grandmother's intelligence was also in normal range, and she also had a spontaneous abortion. The clinical features of the mother and grandmother correspond with “microcephaly-digital abnormalities-normal intelligence” syndrome. Both the mother and the maternal grandmother carried the truncating, Glu73X nonsense mutation in MYCN. Interestingly, a phenotypically similar family has been reported prior to the recognition of MYCN mutations in association with Feingold syndrome [Newbury-Ecob et al., 1999]. Our cases highlight the significantly variable expressivity of a MYCN mutation in Feingold syndrome and support evidence that “microcephaly-digital abnormalities-normal intelligence” syndrome represents a mild form of this genetic entity. These findings indicate that MYCN haploinsufficiency may be involved in other isolated or complex defects of visceral organs and/or brain growth. However, initial observations in patients with VATER association and non-syndromic esophageal atresia did not support this possibility, since no MYCN mutations were detected in these cases [van Bokhoven et al., 2005]. Nevertheless, further studies will be required to elucidate the pathogenic spectrum of MYCN defects.
American Journal of Medical Genetics · 2000 · 11 citations
Imperforate anus in Feingold syndrome
AbstractA father and daughter had the characteristic findings of Feingold syndrome including microcephaly, short palpebral fissures, brachydactyly with clinodactyly of fifth fingers, and bilateral syndactyly of second to third and fourth to fifth toes. The infant presented with long-gap esophageal atresia without fistula (type A). Her father, who had short stature and learning disabilities, had congenital imperforate anus with a recto-vesical fistula. This is the first report of distal intestinal atresia in Feingold syndrome.
Ultrasound in Obstetrics and Gynecology · 2007 · 1 citations · open access
P44.05: Feingold syndrome with ring chromosome 13
AbstractFeingold syndrome, also known as MODED (microcephaly-oculo-digito-esophageal-duodenal) syndrome is a clinically variable autosomal dominant disorder comprising hand and foot abnormalities, microcephaly short palpebral fissures, learning disability and esophageal and duodenal atresia. At least 79 patients in 25 families have been reported. Overall patterns of this syndrome exhibit marked intrafamilial variability, particularly with regard to gastrointestinal manifestations and anal atresia was reported in a single case. A recent review suggested that all patients have hand anomalies, foot anomalies 80%, microcephaly 87%, gastrointestinal atresia 38%, heart anomaly 14%, deafness 7% and renal involvement 5%. The gene for Feingold syndrome maps to 2p23-p24, but remains to be identified. A 32-year-old-aged multigravida was referred at 35 weeks of gestational age because of suspicion of duodenal atresia. Fetal ultrasonography showed polyhydramnios and fetal symmetric fetal growth restriction with clinodactyly of both hands and double bubble sign in upper abdomen of fetus. She vaginally delivered a 1560 g (< 10th percentile) head circumference 28.5 cm (< 10th percentile) female at 36 + 5 weeks gestational age. She had short palpebral fissure, cleft palate, absence of thumbs, clinodactyly of 2nd fingers and hypoplasia of 5th fingers in both hands. The examinations revealed multiple anomalies that comprised PDA, VSD and persistent foramen ovale in heart, duodenal atresia and anal atresia with cutaneous fistula. Tapering enteroplasty, duodeno-jejunostomy and cut-back anoplasty were performed at age 3 days. A G-banded karyotype of neonate was ring chromosome 13. The case is the first report Feingold syndrome with ring chromosome 13.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
