DeCure for Developmental delay with short stature, dysmorphic facial features, and sparse hair 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for developmental delay with short stature, dysmorphic facial features, and sparse hair 1 — 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 moduleDevelopmental delay with short stature, dysmorphic facial features, and sparse hair 1 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 developmental delay with short stature, dysmorphic facial features, and sparse hair 1 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.
What the evidence adds up to
The molecular basis of Hallermann-Streiff syndrome, a disorder with craniofacial dysmorphism, eye malformations, sparse hair, short stature, and aspects of premature aging, remains unknown as of a 2018 review. That review proposed future strategies for gene identification but reported no specific gene or drug target.
Variants in the DPH1 gene cause developmental delay, short stature, and sparse hair syndrome (DPH1 syndrome, also called Loucks-Innes syndrome), an ultra-rare severe neurodevelopmental disorder with fewer than 20 reported patients across ethnicities as of 2021. The first Chinese adult with genetically confirmed DPH1 syndrome was described that year, and a summary of all previously reported patients found that developmental delay, unusual skull shape, sparse hair, and facial dysmorphism were consistently present. Dysplastic toenails and dental abnormalities were age-dependent. That patient was the first reported with documented growth hormone deficiency. The authors recommended dental and endocrine checkup in routine follow-up but did not report any drug treatment or clinical trial.
SOFT syndrome (short stature, onychodysplasia, facial dysmorphism, hypotrichosis) is a rare autosomal recessive disease caused by POC1A pathogenic variants. A 2021 case report identified two novel compound heterozygous POC1A variants in one patient and described novel phenotypes: metaphyseal dysplasia that alleviated or disappeared with age, uneven femoral neck density, and stripe-like hyperintensity signal of the metaphysis. No drug or intervention was tested.
A 2020 report described a patient with developmental delay, extremely short stature, small hands, dysmorphic facial features, hearing loss, and epilepsy carrying a de novo 2.76-Mb deletion of 2q36.3q37.1 encompassing TRIP12 and NPPC. TRIP12 haploinsufficiency causes developmental delay with isolated dysmorphic facial features; NPPC haploinsufficiency causes short stature and small hands. No treatment was investigated.
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 Part C Seminars in Medical Genetics · 2018 · 25 citations
Hallermann-Streiff syndrome: A missing molecular link for a highly recognizable syndrome
AbstractThe use of modern next-generation sequencing-based approaches for gene identification has tremendously improved our understanding of the molecular pathogenesis of the great majority of well-known syndromes, whereas only a few remain to be elucidated. Hallermann-Streiff syndrome is such a disorder for which the molecular basis is still unknown although it represents a highly recognizable phenotype. Clinically, patients with Hallermann-Streiff syndrome show typical craniofacial dysmorphism, eye malformations, a distinctive facial appearance, abnormalities of hair and skin, short stature, and, interestingly, they might also present with aspects of premature aging. The clinical diagnosis is mainly given by the very typical facial gestalt of patients. In this review, we (a) summarize the current knowledge on the phenotypic traits, focusing on described classic cases, (b) discuss the missing molecular link, and (c) present innovative future strategies for gene identification.
American Journal of Medical Genetics Part A · 2021 · 5 citations
An adult Chinese patient with developmental delay with short stature, dysmorphic features, and sparse hair (<scp>Loucks‐Innes</scp> syndrome)
AbstractVariants of the diphthamide biosynthesis I (DPH1, OMIM*603527) are associated with developmental delay, short stature, and sparse hair syndrome (DEDSSH/DPH1 syndrome) (OMIM# 616901). Another name is Loucks-Innes syndrome. DPH1 syndrome is an ultrarare and severe neurodevelopmental disorder. Less than 20 patients were reported from different ethnicities. Here, we described the first Chinese adult with genetically confirmed DPH1 syndrome. We summarized previously reported patients in the literature and found that developmental delay, unusual skull shape, sparse hair, and facial dysmorphism were consistently present in all DPH1 syndrome patients. Dysplastic toenails and dental abnormalities are age-dependent characteristics of DPH1 syndrome. Our patient was the first reported patient with documented growth hormone deficiency. Dental and endocrine checkup should be considered in the routine follow-up of DPH1 syndrome patients.
Molecular Medicine Reports · 2021 · 5 citations · open access
Further phenotypic features and two novel <i>POC1A</i> variants in a patient with SOFT syndrome: A case report
AbstractShort stature, onychodysplasia, facial dysmorphism and hypotrichosis (SOFT) syndrome is a rare autosomal recessive disease caused by POC1 centriolar protein A (<em>POC1A</em>) pathogenic variants. However, knowledge of genotypic and phenotypic features of SOFT syndrome remain limited as few families have been examined; therefore, the clinical identification of SOFT syndrome remains a challenge. The aim of the present case report was to investigate the genetic cause of this syndrome in a patient with a short stature, unusual facial appearance, skeletal dysplasia and sparse body hair. Giemsa banding and exome sequencing were performed to investigate the genetic background of the family. Spiral computed tomography and magnetic resonance imaging were used for investigating further phenotypic features of the patient. Exome sequencing identified that <em>POC1A</em> had two compound heterozygous variants, namely c.850_851insG and c.593_605delGTGGGACGTGCAT, which, to the best of our knowledge, have not been reported elsewhere. Novel phenotypes were also identified as follows: i) Metaphyseal dysplasia was alleviated (and/or even disappeared) with age; ii) the density of the femoral neck was uneven and the hyperintensity signal of the metaphysis was stripe‑like. Thus, the present case report expands the knowledge regarding phenotypic and genotypic features of SOFT syndrome.
Human Genome Variation · 2020 · 3 citations · open access
De novo 2q36.3q37.1 deletion encompassing TRIP12 and NPPC yields distinct phenotypes
AbstractAbstract We report a patient with developmental delay, extremely short stature, small hands, dysmorphic facial features, hearing loss, and epilepsy carrying a de novo 2.76-Mb deletion of 2q36.3q37.1, including TRIP12 and NPPC . TRIP12 haploinsufficiency causes developmental delay with isolated dysmorphic facial features, whereas NPPC haploinsufficiency causes short stature and small hands. This is the first report of a unique phenotype, which is secondary to a microdeletion encompassing TRIP12 and NPPC .
Annals of Translational Medicine · 2017 · 0 citations · open access
AB024. Etiology of recognizable or unclassified overgrowth syndrome
AbstractBackground: Overgrowth syndromes comprise a group of disorders associated with excessive growth and other features such as facial dysmorphism, developmental delay (DD)/intellectual disability (ID), congenital anomalies, neurological problems and an increased risk of neoplasia. Here, we report 13 children with overgrowth syndrome. Methods: A total of 13 unrelated patients with overgrowth syndrome were recruited. All of them presented with (I) excessive height >95th percentile with/without (II) DD/ID, and at least two minor features of the following: (i) dysmorphic craniofacial features and (ii) congenital anomalies. Results: Seven patients were diagnosed as Sotos syndrome (SS) whish was confirmed by sequencing or MLPA analysis of NSD1 gene. Five patients had Beckwith-Wiedemann syndrome (BWS) confirmed by methylation PCR. The other patient was found to have interstitial microdeletion of 7q22.1-7q22.3 by array comparative genomic hybridization. All SS patients showed macrocephaly, tall stature, and DD/ID. Among seven patients with SS, 3/7 (42.8%) patients had seizure and thoracolumbar scoliosis; 3/7 (42.8%) patients had attention deficit hyperactivity disorder (ADHD); 1/7 (14.3%) patient was found to have periventricular leukomalacia (PVL) as shown on brain MRI. Among patients with BWS, 4/5 (80%) patients had DD/ID; 3/5 (60%) patients showed hemihypertrophy which is left-side dominant; 2/5 (40%) had umbilical hernia and history of neonatal hypoglycemia; 1/5 was complicated with hepatoblastoma; 1/5 reported intractable seizure requiring antiepileptic medications. Clinical manifestations of the patient with 7q22.1-7q22.3 microdeletion included generalized excessive growth, prominent forehead, mild hypertelorism, undescended/retractile testis, and global DD. The deletion was starting from nucleotide 102,877,293 extending to nucleotide 105,121,326 which involved 9 genes. Conclusions: Careful clinical examination of patients may allow the delineation of clinically recognizable overgrowth conditions. A detailed molecular analysis of the rearranged regions may provide the clues for identification of the genes involved in growth regulation.
Wiedemann-Steiner syndrome diagnosis in a patient with clinical suspicion of Rubinstein-Taybi syndrome
AbstractWe report a 14-year-old Brazilian female patient, the only child of non-consanguineous parents, who had global developmental delay, facial dysmorphisms, and recurrent respiratory and urinary infections. She exhibited behavioral immaturity and learning difficulties, without stereotypies or aggressive behavior. Growth hormone replacement began at nine years of age due to short stature. Physical examination revealed multiple dysmorphic features, including craniofacial anomalies (bitemporal narrowing, arched and thick eyebrows, synophrys, long eyelashes, downslanting palpebral fissures, ptosis, hypertelorism, low-set ears, bulbous nasal tip, low hanging columella, apparent short philtrum, and high-arched palate, and microdontia) and digital anomalies (mild clinodactyly, broad thumbs and halluces, hallux valgus, and digital pads). Additional findings included diffuse hypertrichosis, delayed bone age, strabismus, and recurrent infections. Based on clinical scoring, Rubinstein-Taybi syndrome (RSTS, OMIM #180849) was initially suspected. However, whole exome sequencing identified a heterozygous pathogenic variant in the KMT2A gene (OMIM *159555), confirming a diagnosis of Wiedemann-Steiner syndrome (WSTS, OMIM #605130). These two conditions have extensive phenotypic overlap, and the presence of shared features in this patient further challenged the clinical diagnosis. This case shows it is generally more readily recognized to suspect a well-described and widely reported syndrome than a less characterized and rarer one. Notably, GestaltMatcher analysis of facial photographs reinforced the diagnosis, ranking WSTS as the most likely (distance: 0.566) and RSTS as the second most suggestive condition (distance: 0.602).
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.
