ORPHA:597874
MTHFS-related developmental delay-microcephaly-short stature-epilepsy syndrome
Publications
436
74.7th percentile
Trials
0
Interventional, condition-specific
Researchers
143
Distinct authors in sample
Gene link
MTHFS
Strong
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare, genetic, neurometabolic disease characterized by microcephaly, short stature, , cerebral hypomyelination, severe global , and spasticity. Macrocytic anemia and hyperthermia have also been reported in association. Brain imaging reveals delayed myelination with minimal progression over time, mild cerebellar atrophy and/or thin corpus callosum.
How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0032705
- OMIM:618367
- UMLS:C5193057
Additional Mondo synonyms (3)
5,10-methenyltetrahydrofolate synthetase deficiency · NEDMEHM · NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, EPILEPSY, AND HYPOMYELINATION
Research stages
Trial readiness signals
Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”
3/6 stages with a signal
No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.
- Gene identifiedPresent
Strong — MTHFS
- LiteraturePresent
436 matched papers (289 in last 10 years) Source
- Phenotype characterisedPresent
32 HPO annotations (e.g. Exaggerated startle response; Seizure; Focal emotional seizure with laughing) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialNot found
No matched interventional trial under our ClinicalTrials.gov rules
Biology
Genes and phenotypes
Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.
Do we know what causes it?
Yes — we know a specific gene responsible (MTHFS).
GenCC classification: Strong.
Phenotypes (Monarch / HPO)
32
Associated phenotypes · MONDO:0032705
- Exaggerated startle response
- Seizure
- Focal emotional seizure with laughing
- Microcephaly
- Delayed speech and language development
Showing 5 of 32 — open Monarch for the full list.
Animal models (Monarch / Alliance)
None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.
Monarch fetch 2026-07-27
Therapies
Designations, candidates, and chemicals
FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.
Orphan designation (FDA · EMA)
No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.
Open Targets candidates
No drugs or clinical candidates returned for this Mondo ID on Open Targets.
CTD chemicals (MyDisease.info)
No CTD chemical associations returned for this Mondo ID.
Literature
Is anyone studying this?
436
436 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.
436 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).
289 in the last 10 years · medium confidence · 74.7th percentile (publications denominator)
Phrase hits: 18 · MeSH hits: 0
Who's working on it?
143
Distinct author names in 18 sampled papers — named people below.
Who's working on it?
No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.
- 01Ferreira CR4 papers · 2023
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Papers in Europe PMC - 02
- 03Blau N2 papers · 2023
Division of Metabolism, University Children's Hospital, Zürich, Switzerland. Electronic address: nenad.blau@kispi.uzh.ch.
Papers in Europe PMC - 04
- 05Li L2 papers · 2020
Reproductive Medicine & Prenatal Diagnosis Center, First Hospital of Jilin University, Changchun, China.
Papers in Europe PMC - 06
- 07
- 08van Karnebeek CDM2 papers · 2022
Department of Pediatrics, Amsterdam UMC, Amsterdam, The Netherlands. clara.vankarnebeek@radboudumc.nl.
Papers in Europe PMC - 09
- 10
Clinical research
Is a treatment being tested?
0
interventional trials for this specific condition
No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).
Data as of 9 September 2026 · last trial check 9 September 2026
No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.
medium confidence · 38.6th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.
See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.
Other registries (secondary)
Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.
raw 60 · after dedupe 60 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 60 · dropped 0 · fetched 2026-07-27
Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri
No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).
Uncertain / not reviewed (60)
- ctis·2025-525040-18-00·Authorised·DECREASE-IPC 2025-068 : De-Ecalating neoadjuvant Chemoimmunotherapy in early triple-negative BREASt cancer
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-523650-14-00·Authorised·functional imaging of digital osteoarthritis and rheumatoid arthritis using 99mTc-NTP15-5 in nuclear medicine : phase II clinical study
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524054-34-00·Authorised·An Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Salanersen (BIIB115) in Participants Aged 15-60 Years With Spinal Muscular Atrophy Who Are Either Treatment-Naïve or Have Previously Been Treated With Risdiplam
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-523994-41-00·Authorised·A Phase III, Randomized, Double-blind, Parallel-group, Placebo-controlled Multicenter Study to Evaluate the Effect of Elecoglipron in Reducing Renal Outcomes and Mortality in Participants with Chronic Kidney Disease (Elevate-CKD)
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-525097-11-00·Authorised·Phase 3 Randomized Study of Teclistamab and Talquetamab (Tec-Tal) Versus Daratumumab and Lenalidomide (DR) in Minimal Residual Disease (MRD) Positive Patients With Newly Diagnosed Multiple Myeloma After Autologous Hematopoietic Stem Cell Transplantation (TiTan)
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-525185-21-00·Authorised·IKF-099/D-FLOT-TNT
Total Neoadjuvant Treatment with preoperative FLOT/Durvalumab plus postoperative Durvalumab for Resectable Gastroesophageal Adenocarcinoma
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524282-24-00·Authorised·A Phase 3b, Open-Label Study of Crinecerfont to Evaluate Androgen Reduction and Related Outcomes in Adults With Classic Congenital Adrenal Hyperplasia
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-525727-24-00·Authorised·Prospective, multicentre, open-label, single arm trial on contraceptive efficacy, safety and tolerability of LPRI-CF113 (Drospirenone 4 mg + 2.8 mg) during 13 cycles.
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-526804-59-00·Authorised·Real-World Effectiveness of the Adjuvanted RSVPreF3 Vaccine in Adults ≥60 Years: A Pragmatic Randomized Trial (BronquiVal)
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-523435-18-00·Authorised·Colchicine for the Reduction of Dependency and Vascular Events after an Acute Intracerebral Hemorrhage (CoVasc-ICH2)
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-525620-23-00·Authorised·Local and systemic immune modulation by Rilvegostomig (AZD2936) in the treatment of advanced gastric cancer (RILVE Project)
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-523933-24-00·Authorised·A Randomized, Open-label, Parallel-group Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Elecoglipron Compared with Oral Semaglutide in Adults with Type 2 Diabetes Mellitus (Eluminate-2)
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-525242-29-00·Authorised·A Phase III, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elafibranor in Adult Participants with Primary Sclerosing Cholangitis
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-526209-13-00·Authorised·A more sustainable perioperative treatment regimen for gastroesophageal cancer —replacing 5-FU with capecitabine within the FLOT regimen
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524336-19-00·Authorised·A Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Switching to a Regimen of Broadly Neutralizing
Antibodies Teropavimab and Zinlirvimab in Combination with Capsid Inhibitor Lenacapavir Twice Yearly in Virologically Suppressed Adults with HIV-1 Infection on Stable Oral Treatment Regimens
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524335-39-00·Authorised·A Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Switching to Long-acting Antiretroviral Therapy of Broadly Neutralizing Antibodies Teropavimab and Zinlirvimab in Combination With the Capsid Inhibitor Lenacapavir Twice-Yearly Versus Cabotegravir and Rilpivirine Every 8 Weeks in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524873-17-00·Authorised·A Phase 3, Double-blinded, Vehicle-controlled Trial to Investigate the Efficacy and Safety of Twice-daily Delgocitinib Cream in Adult Participants with Lichen Sclerosus During a 12-Week Initial Treatment Period Followed by a 40-Week Continuation Treatment Period
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-525736-42-00·Authorised·A PHASE II, SINGLE ARM, OPEN LABEL, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF CEVOSTAMAB IN COMBINATION WITH POMALIDOMIDE AND DEXAMETHASONE IN PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED A PRIOR BCMA TARGETING CAR T-CELL THERAPY
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524249-29-00·Authorised·A placebo-controlled comparability study to compare two presentations of cagrilintide for weight management in participants with overweight or obesity
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-522227-99-00·Authorised·A randomized, placebo-controlled, double-blind Phase 3 study to evaluate the efficacy, safety and tolerability of votoplam in participants with Huntington’s Disease
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524711-36-00·Authorised·A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2026-525162-21-00·Authorised·A Phase 2a, multi centric, open label clinical study to explore the safety and tolerability, the pharmacokinetics and pharmacodynamics profile and first signs of efficacy of PTI5803 administered as adjunctive therapy with a 3-dose escalation regimen in patients >= 14 years of age with drug-resistant seizures associated to focal cortical dysplasia, followed by an optional open-label extension study.
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-523662-24-00·Authorised·Phase 3 Single-Arm Open-Label Study to Evaluate the Efficacy and Safety of Zodasiran in Adolescent Subjects (age 12 to <18 years) with Homozygous Familial Hypercholesterolemia (SPRUCE)
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524169-26-00·Authorised·An open label multicenter phase II study to investigate the efficacy, safety and
tolerability of the Obe-cel in patients with minimal residual disease (MRD) of
Philadelphia negative (Ph neg) B-precursor acute lymphoblastic leukaemia (B-ALL) - GMALL-OBECEL
Uncertain — At least one provider returned uncertain or parent-category.
- ctis·2025-524576-28-00·Authorised·Intrathecal Administration of MELPIDA For Hereditary Spastic Paraplegia Type 50 (SPG50): A multicenter Phase 3, Open-Label Trial with Matched Prospective Concurrent Control Arm (CT-MEL-03)
Uncertain — At least one provider returned uncertain or parent-category.
Where to find support
Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.
Orphanet entry for MTHFS-related developmental delay-microcephaly-short stature-epilepsy syndrome — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.
Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.
How we counted this
Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.
("MTHFS-related developmental delay-microcephaly-short stature-epilepsy syndrome" OR "5,10-methenyltetrahydrofolate synthetase deficiency" OR "NEDMEHM" OR "NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, EPILEPSY, AND HYPOMYELINATION") OR ("MTHFS" OR "MTHFS syndrome" OR "MTHFS-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"MTHFS-related developmental delay-microcephaly-short stature-epilepsy syndrome" OR "5,10-methenyltetrahydrofolate synthetase deficiency" OR "NEDMEHM" OR "NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, EPILEPSY, AND HYPOMYELINATION"
Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase; with hits: phrase
Run this search on ClinicalTrials.gov
Confidence reasoning
- Preferred label is multi-word and distinctive
- No synonyms dropped by stoplist
- No label/synonym collisions with other diseases in this corpus
- Publication count (436) is high for prevalence class "<1 / 1 000 000" — confidence capped at medium
Ingested 2026-07-26T02:11:31.763Z