ORPHA:300496
Multiple congenital anomalies-hypotonia-seizures syndrome type 2
Also known as: MCAHS type 2
Publications
4,880
Trials
0
Interventional, condition-specific
Researchers
829
Distinct authors in sample
Gene link
PIGA
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare, genetic, lethal, neurometabolic syndrome characterized by multiple, variable, cardiac (systolic murmur, atrial septal defect), urinary (duplicated collecting system, vesicoureteral reflux) and central nervous system (thin corpus callosum, cerebellar hypoplasia) malformations associated with , early-onset epileptic , and myoclonic . Craniofacial dysmorphism (prominent occiput, enlarged fontanel, fused metopic suture, upslanted palpebral fissures, overfolded helix, depressed nasal bridge, anteverted nose, malar flattening, microstomy with downturned corners, Pierre-Robin sequence, high arched palate, short neck) and other manifestations (joint contractures, hyperreflexia, dysplastic nails, ) are also observed.
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:0010466
- OMIM:300868
- UMLS:C3275508
Additional Mondo synonyms (11)
DEE20 · GPIBD4 · MCAHS2 · PIGA multiple congenital anomalies/dysmorphic syndrome-intellectual disability · developmental and epileptic encephalopathy 20 · epileptic encephalopathy, early infantile, 20 · glycosylphosphatidylinositol biosynthesis defect 4 · multiple congenital anomalies-hypotonia-seizures syndrome 2 · multiple congenital anomalies-hypotonia-seizures syndrome 2, X-linked recessive · multiple congenital anomalies-hypotonia-seizures syndrome type 2 · multiple congenital anomalies/dysmorphic syndrome-intellectual disability caused by mutation in PIGA
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
Definitive — PIGA
- LiteraturePresent
4,880 matched papers (2,711 in last 10 years) Source
- Phenotype characterisedPresent
196 HPO annotations (e.g. Seborrheic dermatitis; Microcephaly; Ichthyosis) 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 (PIGA).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
196
Associated phenotypes · MONDO:0010466
- Seborrheic dermatitis
- Microcephaly
- Ichthyosis
- Short palpebral fissure
- Arrhinencephaly
Showing 5 of 196 — 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 2026-07-29
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?
4,880
4,880 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.
4,880 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).
2,711 in the last 10 years · low confidence
Phrase hits: 83 · MeSH hits: 0
Who's working on it?
829
Distinct author names in 83 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.
- 01Brodsky RA5 papers · 2017
Johns Hopkins Division of Hematology, Baltimore, MD, USA.
Papers in Europe PMC - 02Helbig I4 papers · 2022
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
Papers in Europe PMC - 03Jezela-Stanek A4 papers · 2021
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
Papers in Europe PMC - 04Kinoshita T4 papers · 2016
Department of Immunoregulation, Research Institute for Microbial Diseases, and World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Papers in Europe PMC - 05Knaus A4 papers · 2024
Institut für Medizinische Genetik und Humangenetik, Charité Universitätsmedizin Berlin, 13353, Berlin, Germany.
Papers in Europe PMC - 06
- 07Berkovic SF3 papers · 2022
Epilepsy Research Centre, Department of Medicine, University of Melbourne (Austin Health), Heidelberg, VIC, Australia
Papers in Europe PMC - 08Chen X3 papers · 2026
Tianjin Children's Hospital (Children's Hospital of Tianjin University), No. 238 Longyan Road, Beichen District, 300134, Tianjin, China.
Papers in Europe PMC - 09Francisco R3 papers · 2023
UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Lisboa, Portugal.
Papers in Europe PMC - 10Jaeken J3 papers · 2023
Metabolic Center, Department of Pediatrics, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium.
Papers in Europe PMC
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 11 September 2026 · last trial check 11 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.
low 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 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-30
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).
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 Multiple congenital anomalies-hypotonia-seizures syndrome type 2 — 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.
("Multiple congenital anomalies-hypotonia-seizures syndrome type 2" OR "MCAHS type 2" OR "DEE20" OR "GPIBD4" OR "MCAHS2" OR "PIGA multiple congenital anomalies/dysmorphic syndrome-intellectual disability" OR "developmental and epileptic encephalopathy 20" OR "epileptic encephalopathy, early infantile, 20" OR "glycosylphosphatidylinositol biosynthesis defect 4" OR "multiple congenital anomalies-hypotonia-seizures syndrome 2" OR "multiple congenital anomalies-hypotonia-seizures syndrome 2, X-linked recessive" OR "multiple congenital anomalies/dysmorphic syndrome-intellectual disability caused by mutation in PIGA") OR ("PIGA" OR "PIGA syndrome" OR "PIGA-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Multiple congenital anomalies-hypotonia-seizures syndrome type 2" OR "MCAHS type 2" OR "DEE20" OR "GPIBD4" OR "MCAHS2" OR "PIGA multiple congenital anomalies/dysmorphic syndrome-intellectual disability" OR "developmental and epileptic encephalopathy 20" OR "epileptic encephalopathy, early infantile, 20" OR "glycosylphosphatidylinositol biosynthesis defect 4" OR "multiple congenital anomalies-hypotonia-seizures syndrome 2" OR "multiple congenital anomalies-hypotonia-seizures syndrome 2, X-linked recessive" OR "multiple congenital anomalies/dysmorphic syndrome-intellectual disability caused by mutation in PIGA"
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 (4880) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-27T12:40:51.814Z