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ORPHA:778

Rett syndrome

low confidenceDisorder

Publications

25,048

Trials

65

Interventional, condition-specific

Researchers

1,103

Distinct authors in sample

Gene link

MECP2

Definitive

Readiness

6/6

Stages with a signal

Clinical definition (Orphanet)

A rare severe, X-linked, neurodevelopmental disorder characterized by rapid developmental regression in infancy, partial or complete loss of purposeful hand movements, loss of speech, gait abnormalities, and stereotypic hand movements, commonly associated with deceleration of head growth, severe , , and breathing abnormalities. The disorder has a clinical course and may associate various comorbidities including gastrointestinal diseases, scoliosis, and behavioral disorders.

How rare: 1-9 / 100 000 — about one to nine people per hundred thousand.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (6)

RTS · RTT · Rett syndrome, X-linked dominant · Rett syndrome, atypical, X-linked dominant · Rett syndrome, preserved speech variant, X-linked dominant · Rett’s disease

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.”

6/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — MECP2

  2. LiteraturePresent

    25,048 matched papers (14,790 in last 10 years) Source

  3. Phenotype characterisedPresent

    64 HPO annotations (e.g. Gait disturbance; Progressive microcephaly; Motor stereotypy) Source

  4. Animal modelPresent

    53 genotype models (Mus musculus, Danio rerio) Source

  5. Orphan designationPresent

    6 FDA · 14 EMA designations (6 FDA orphan-indication approvals) — e.g. tianeptine Source

  6. Interventional trialPresent

    65 matched on ClinicalTrials.gov (12 recruiting in sample)

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 (MECP2).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

64

Associated phenotypes · MONDO:0010726

  • Gait disturbance
  • Progressive microcephaly
  • Motor stereotypy
  • Global developmental delay

Showing 4 of 64 — open Monarch for the full list.

Animal models (Monarch / Alliance)

53

Model associations linked to this Mondo ID

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)

20

Designations · 6 with FDA orphan-indication approval

  • FDA tianeptineRett Syndrome · 2018-03-08 · Not FDA Approved for Orphan Indication
  • FDA cannabidivarinRett Syndrome · 2016-11-30 · Not FDA Approved for Orphan Indication
  • FDA 6'-(R)-Methyl-5-O-(5-amino-5,6-dideoxy-a-L-talofuranosyl)- paromamine sulfateRett Syndrome · 2016-11-03 · Not FDA Approved for Orphan Indication
  • FDA sarizotanRett Syndrome · 2015-07-07 · Not FDA Approved for Orphan Indication
  • FDA TrofinetideRett Syndrome · 2015-02-11 · Not FDA Approved for Orphan Indication
  • FDA vatiquinoneRett Syndrome · 2014-11-17 · Not FDA Approved for Orphan Indication
  • EMA sarizotan hydrochlorideTreatment of Rett syndrome · 28/07/2015 · PositiveEMA designation
  • EMA extract from Cannabis flower, containing high levels of cannabidiolic acid andTreatment of Rett syndrome · 25/03/2025 · PositiveEMA designation

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

23

Drugs / clinical candidates · MONDO_0010726

CTD chemicals (MyDisease.info)

1 associated chemical · 27 pathways. Therapeutic evidence is listed first when present — not a treatment recommendation.

  • UA 0713 · therapeutic

Pathways: Adherens junction; Insulin signaling pathway; Insulin resistance; Hepatitis B; HTLV-I infection; Viral carcinogenesis; Hemostasis; Developmental Biology

MyDisease.info · MONDO:0010726

Literature

Is anyone studying this?

25,048

25,048 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

25,048 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).

14,790 in the last 10 years · low confidence

Phrase hits: 14,894 · MeSH hits: 472

Open Europe PMC search

Who's working on it?

1,103

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Rajagopalan K6 papers · 2026

    Anlitiks Inc., Windermere, FL, United States.

    Papers in Europe PMC
  2. 02
    Rashid N6 papers · 2026

    Medical Affairs, Acadia Pharmaceuticals Inc., San Diego, CA, United States.

    Papers in Europe PMC
  3. 03
    Fagiolini M5 papers · 2026

    F.M. Kirby Neurobiology Division, Boston Children's Hospital, Boston, MA, USA.

    Papers in Europe PMC
  4. 04
    Marsh ED5 papers · 2026

    Departments of Neurology and Pediatrics, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA, USA.

    Papers in Europe PMC
  5. 05
    Benke TA4 papers · 2026

    School of Medicine, Departments of Pediatrics, Neurology and Pharmacology, Children's Hospital of Colorado and University of Colorado, Aurora, CO, USA.

    Papers in Europe PMC
  6. 06
    Downs J4 papers · 2026

    The Kids Research Institute Australia, The Centre for Child Health Research, University of Western Australia, Perth, WA, Australia.

    Papers in Europe PMC
  7. 07
    Gogliotti RG4 papers · 2026

    Department of Molecular Pharmacology and Neuroscience, Loyola University Chicago, IL 60660, USA.

    Papers in Europe PMC
  8. 08
    Koetsier J4 papers · 2026

    Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD, Maastricht, The Netherlands.

    Papers in Europe PMC
  9. 09
    Neul JL4 papers · 2026

    Department of Pediatrics, Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN, USA.

    Papers in Europe PMC
  10. 10
    Niswender CM4 papers · 2026

    Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: Colleen.niswender@vanderbilt.edu.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

65

interventional trials for this specific condition

65 interventional trials matched this specific condition name; 12 currently recruiting in our sample.

Data as of 11 September 2026 · last trial check 28 July 2026

65 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 97.8th percentile).

low confidence · 97.8th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

65 interventional trials matched after quoted-phrase search and title/condition post-filter.

Observational and natural-history studies

31 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

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 30 · after dedupe 29 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 29 · dropped 0 · fetched 2026-07-29

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 (29)

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 Rett syndrome — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This 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.

("Rett syndrome" OR "Rett syndrome, X-linked dominant" OR "Rett syndrome, atypical, X-linked dominant" OR "Rett syndrome, preserved speech variant, X-linked dominant" OR "Rett’s disease") OR (MESH:"Rett Syndrome") OR ("MECP2" OR "MECP2 syndrome" OR "MECP2-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Rett Syndrome

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Rett syndrome" OR "Rett syndrome, X-linked dominant" OR "Rett syndrome, atypical, X-linked dominant" OR "Rett syndrome, preserved speech variant, X-linked dominant" OR "Rett’s disease"

Interventional trials matched via: both (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 65 interventional · 31 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: ok — strategies attempted: phrase, mesh; with hits: phrase, mesh

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: RTS; RTT

Confidence reasoning

  • Preferred label is short or not clearly distinctive
  • 2 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus

Ingested 2026-07-26T15:19:25.077Z