DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Pallister-Hall syndrome — screening already-approved drugs against its 20-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePallister-Hall syndrome maps to a 20-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 pallister-hall 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
interleukin 6 (IL6) — IL6 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…
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RCSB Protein Data Bank · entry 1ALU · 1.9 Å · ligand L(+)-TARTARIC ACID (TLA). Experimental structure, not a prediction.
What the evidence adds up to
Pallister-Hall syndrome is a very rare genetic disorder first described in 1980. Its core features include central polydactyly and hypothalamic hamartoma, which can be associated with several additional anomalies including imperforate anus, renal anomalies, bifid epiglottis, high-arched palate, and external ear anomalies. Originally thought to be lethal in the perinatal period, milder phenotypic forms with a normal lifespan are now recognised. Endocrine manifestations are mostly related to hypothalamic hamartoma and rarely reveal the disease; one 18-year-old man had his diagnosis delayed until hospitalisation for acute adrenal insufficiency. A male infant with hypothalamic tumour, hypopituitarism, dysplastic metacarpals, micropenis and remarkable hypoglycaemia was treated with hydrocortisone, thyroid hormone, NaCl, fludrocortisone acetate and GH, and grew well on this therapy.
A 4-year-old girl with Pallister-Hall syndrome, localised epilepsy due to hypothalamic hamartoma, severe mental retardation, high-arched palate, preauricular tags, renal abnormalities and hand polydactyly underwent dental treatment under general anaesthesia. Her epilepsy was partially controlled with sodium valproate 200 mg, and she continued to have minor seizure activity a few times a day. During intubation a bifid epiglottis was noted, a congenital malformation reported in 40% of patients with Pallister-Hall syndrome. The authors concluded that preparation for difficult intubation was essential, although in this case a difficult airway was not encountered, and that good control of epilepsy would contribute to decreasing perioperative morbidity.
Two patients described in 1991 had the usual features of Hall-Pallister syndrome including diencephalic anomalies but without hamartoblastomas, suggesting an extension of the definition. The syndrome is an autosomal dominant disorder characterised by varying combinations of a spectrum of abnormalities. No drug treatments beyond hormone replacement for hypopituitarism and anticonvulsants for epilepsy are described in these abstracts; no clinical trials of any drug for Pallister-Hall syndrome are reported. What is still missing is any systematic trial design, patient stratification by phenotype severity, and funding for natural history studies or targeted therapy development.
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 · 1991 · 24 citations
Extending the Pallister‐Hall syndrome to include other central nervous system malformations
AbstractHall-Pallister syndrome is defined by specific facial anomalies, post axial polydactyly, imperforate anus, and brain anomalies including a rare diencephalic mass, hypothalamic hamartoblastoma. In this article, two patients are described with the usual features of Hall-Pallister syndrome, including diencephalic anomalies, but without hamartoblastomas. These patients may suggest an appropriate extension of the definition of the Hall-Pallister syndrome.
Indian Journal of Anaesthesia · 2018 · 7 citations · open access
Bifid epiglottis, high-arched palate, and mental disorder in a patient with Pallister–Hall syndrome
AbstractSir, Pallister–Hall syndrome is a rare autosomal recessive disease first described in 1980 by Philip Pallister and Judith Hall.[1] Craniofacial anomalies include bifid epiglottis, high-arched palate, and external ear anomalies.[12] In addition, polydactyly and hypothalamic hamartoma causing hypopituitarism and neurological disorders are also commonly seen.[3] Imperforate anus and renal anomalies occur frequently. We report the anaesthetic management of a girl with Pallister–Hall syndrome under general anaesthesia. A 4-year-old female, 98.4 cm in height and 21.1 kg in weight, body mass index 21.8, with Pallister–Hall syndrome, was scheduled for dental treatment under general anaesthesia. She was diagnosed to have localized epilepsy due to hypothalamic hamartoma for which she was receiving sodium valproate 200 mg. With this medication, her epilepsy was partially under control and she continued to have minor seizure activity, a few times a day. Her neurological status was poor with severe mental retardation. In addition, we could not communicate with her. Her clinical features included a high-arched palate and preauricular tags. The clinical assessment of her airway was difficult due to uncooperative behavior [Figure 1]. In addition, she had renal abnormalities and hand polydactyly. No abnormal findings were observed on chest X-ray and laboratory data.Figure 1: High-arched palateShe was brought to the operating room after peripheral intravenous access was obtained. Anaesthesia was induced with fentanyl 50 μg, atropine 0.2 mg, and propofol 40 mg after preoxygenation and with monitoring of SpO2, electrocardiography, blood pressure, and heart rate. After the loss of consciousness, mask ventilation without an oral airway was easy. Then, rocuronium 12 mg was administered. During intubation using a 5.0-mm uncuffed nasotracheal tube by direct laryngoscopy, a bifid epiglottis was noted [Figure 2]. Anaesthesia was maintained with end-tidal isoflurane 0.9–1.8 in air and oxygen. Haemodynamic parameters were stable, bispectral index value was 54–68, spectral edge frequency was 16–23 Hz, signal quality index was 95%, and EtCO2 was 35–45 mmHg. Dental treatment was completed in 109 min without any surgical problems. There was minimal blood loss during operation, and she received a total of 303 mL lactated Ringer's solution with 1% glucose. Urine volume was 80 mL. After extubation, her postoperative stay was uneventful, and she left the hospital 1 day later.Figure 2: Bifid epiglottis before intubation (left side) and during intubation (right side)Pallister–Hall syndrome is an autosomal dominant disorder characterized by varying combinations of a spectrum of abnormalities. However, there was rare case report about anaesthetic management in literature.[2] The importance of anaesthetic management was safe airway management and to avoid epilepsy. In dental treatment, nasal intubation is usually performed, as it provides unrestricted access to the mouth and facilitates insertion of instrumentation. Airway management for patient with craniofacial disorders poses many challenges.[4] In this case, difficult intubation was especially anticipated because of the presence of high-arched palate and the preoperative airway assessment. During the induction of general anaesthesia, difficult airway cart and expertise should be made available and checked. Intubating stylet, video laryngoscope, fiberscope, or tube exchanger should be available. Airway management depends on evaluation of the abnormalities in each case, and modifications of technique might be needed to decrease the risk of airway complications. In this case, we found a bifid epiglottis, which is a congenital malformation defined as a midline cleft of the epiglottis. It presents as a component of multiple anomalies as a syndromic constituent of malformation syndromes. It was reported in 40% of patients with Pallister–Hall syndrome.[2] It is typically asymptomatic but may be associated with stridor chronic, aspiration, and rarely airway obstruction. Epilepsy is a serious neurological disorder during general anaesthesia. It can be seen as a result of imbalance between excitatory and inhibitory neuronal activity.[5] Appropriate perioperative management of antiepileptic drugs therapy is important to maintain epilepsy control. Anaesthesiologists need to be aware of the pharmacological properties of commonly used drugs. In patients with a history of status epilepticus, regular medications should be taken on the morning of general anaesthesia. Isoflurane has well-characterized anticonvulsant properties of refractory status epilepticus.[5] In addition, propofol was administered to avoid epileptic activity during the induction of anaesthesia. As hyperventilation might decrease cerebral blood flow leading to epilepsy, we had maintained EtCO2 within normal level. We concluded that preparation for a difficult intubation was essential, although in previous reports and in our case, a difficult airway was not encountered. In addition, good control of epilepsy would contribute in decreasing perioperative morbidity. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
An Infant Case of Pallister-Hall Syndrome Treated with Hormone Replacement.
AbstractPallister-Hall syndrome was first described by Hall et al. in 1980. This syndrome is characterized by hypothalamic hamartoblastoma, hypopituitarism, polydactyly, imperforate anus and other anomalies. We report a case of a male infant with hypothalamic tumor, hypopituitarism, dysplastic metacarpals, micropenis and remarkable hypoglycemia. He has been treated with hydrocortisone, thyroid hormone, NaCl, fludrocortisone acetate and GH. He has grown well on this therapy.
Clinical Case Reports · 2022 · 2 citations · open access
Pallister–Hall syndrome diagnosed in a young man after an acute adrenal crisis
AbstractPallister-Hall syndrome (PHS) is a very rare genetic disorder. The diagnosis is usually suspected at the young age when a hypothalamic hamartoma is associated with polydactyly. Endocrine manifestations are mostly related to hypothalamic hamartoma and rarely reveal the disease. We report the case of an 18-year-old young man in whom the diagnosis of PHS was delayed until his hospitalization in the endocrinology department for acute adrenal insufficiency.
International Journal of Cell Science & Molecular Biology · 2017 · 1 citations · open access
Psychiatric and Neuropsychological Features of Pallister-Hall Syndrome. A Mini Review and Case Report
AbstractPallister-Hall syndrome is a rare polimal formative syndrome, first described in 1980. The core features include central polydactyly and hypothalamic hamartoma, which can be associated with several additional anomalies. Originally thought to be lethal in the perinatal period, it was more recently recognized that milder phenotypic forms of the syndrome exist, in individuals with a normal lifespan.
Greater South Information System · 2022 · 0 citations · open access
Pallister–Hall syndrome diagnosed in a young man after an acute adrenal crisis
AbstractPallister-Hall syndrome (PHS) is a very rare genetic disorder. The diagnosis is usually suspected at the young age when a hypothalamic hamartoma is associated with polydactyly. Endocrine manifestations are mostly related to hypothalamic hamartoma and rarely reveal the disease. We report the case of an 18-year-old young man in whom the diagnosis of PHS was delayed until his hospitalization in the endocrinology department for acute adrenal insufficiency.
Greater South Information System · 2022 · 0 citations · open access
Pallister–Hall syndrome diagnosed in a young man after an acute adrenal crisis
AbstractPallister-Hall syndrome (PHS) is a very rare genetic disorder. The diagnosis is usually suspected at the young age when a hypothalamic hamartoma is associated with polydactyly. Endocrine manifestations are mostly related to hypothalamic hamartoma and rarely reveal the disease. We report the case of an 18-year-old young man in whom the diagnosis of PHS was delayed until his hospitalization in the endocrinology department for acute adrenal insufficiency.
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.
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