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ORPHA:217335

RIN2 syndrome

low confidenceDisorder

Also known as: MACS syndrome · Macrocephaly-alopecia-cutis laxa-scoliosis syndrome · RIN2 deficiency · Tall forehead-sparse hair-skin hyperextensibility-scoliosis syndrome

Publications

792

Trials

0

Interventional, condition-specific

Researchers

337

Distinct authors in sample

Gene link

RIN2

Definitive

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

RIN2 syndrome, formerly known as macrocephaly, alopecia, cutis laxa and scoliosis (MACS) syndrome, is a very rare inherited connective tissue disorder characterized by macrocephaly, sparse scalp hair, soft-redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rarer manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly have also been reported.

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.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (2)

macrocephaly-alopecia-cutis laxa-scoliosis syndrome · tall forehead-sparse hair-skin hyperextensibility-scoliosis syndrome

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.

  1. Gene identifiedPresent

    Definitive — RIN2

  2. LiteraturePresent

    792 matched papers (559 in last 10 years) Source

  3. Phenotype characterisedPresent

    74 HPO annotations (e.g. Abnormal lip morphology; Gingival overgrowth; Hyperextensible skin) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. 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 (RIN2).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

74

Associated phenotypes · MONDO:0013115

  • Abnormal lip morphology
  • Gingival overgrowth
  • Hyperextensible skin
  • Hirsutism
  • Infra-orbital fold

Showing 5 of 74 — 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?

792

792 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.

792 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).

559 in the last 10 years · low confidence

Phrase hits: 45 · MeSH hits: 1

Open Europe PMC search

Who's working on it?

337

Distinct author names in 45 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.

  1. 01
    Morava E4 papers · 2017

    1] Department of Pediatrics, Institute for Metabolic and Genetic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands [2] Hayward Genetics Center, Tulane University Medical Center, New Orleans, LA, USA.

    Papers in Europe PMC
  2. 02
    Urban Z4 papers · 2014

    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, United States. Electronic address: urbanz@pitt.edu.

    Papers in Europe PMC
  3. 03
    Callewaert B3 papers · 2025

    Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.

    Papers in Europe PMC
  4. 04
    Gardeitchik T3 papers · 2017

    Department of Pediatrics, Institute for Metabolic and Genetic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands.

    Papers in Europe PMC
  5. 05
    Kornak U3 papers · 2014

    1] Institute of Medical Genetics and Human Genetics, Charité Universitätsmedizin, Berlin, Germany [2] FG Development and Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.

    Papers in Europe PMC
  6. 06
    Li W3 papers · 2026

    BGI Genomics, BGI-Shenzhen, 518083, Shenzhen, China.

    Papers in Europe PMC
  7. 07
    Mohamed M3 papers · 2017

    Department of Pediatrics, Institute for Metabolic and Genetic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands.

    Papers in Europe PMC
  8. 08
    Albrecht B2 papers · 2011

    Department of Human Genetics, University of Essen, Essen, Germany.

    Papers in Europe PMC
  9. 09
    Chen Y2 papers · 2026

    ENT Institute, Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital, Fudan University, Shanghai, China.

    Papers in Europe PMC
  10. 10
    De Paepe A2 papers · 2011
    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. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial.

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.

Observational and natural-history studies

1 observational study matches 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.

None of the matched observational studies is currently listed as 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 5 · after dedupe 5 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 5 · 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).

Uncertain / not reviewed (5)

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 RIN2 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.

("RIN2 syndrome" OR "MACS syndrome" OR "Macrocephaly-alopecia-cutis laxa-scoliosis syndrome" OR "RIN2 deficiency" OR "Tall forehead-sparse hair-skin hyperextensibility-scoliosis syndrome") OR (MESH:"Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis") OR ("RIN2" OR "RIN2-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis

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

"RIN2 syndrome" OR "MACS syndrome" OR "Macrocephaly-alopecia-cutis laxa-scoliosis syndrome" OR "RIN2 deficiency" OR "Tall forehead-sparse hair-skin hyperextensibility-scoliosis syndrome" OR "Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis"

Study-type breakdown: 0 interventional · 1 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

Confidence reasoning

  • Preferred label is short or not clearly distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (792) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T09:49:12.910Z