ORPHA:217335
RIN2 syndrome
Also known as: MACS syndrome · Macrocephaly-alopecia-cutis laxa-scoliosis syndrome · RIN2 deficiency · Tall forehead-sparse hair-skin hyperextensibility-scoliosis syndrome
Publications
45
38.6th percentile
Trials
0
Interventional, condition-specific
Researchers
337
Distinct authors in sample
Gene link
RIN2
Definitive
Readiness
2/6
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0013115
- MeSH:C567770
- OMIM:613075
- UMLS:C2751321
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.”
2/6 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 — RIN2
- LiteraturePresent
45 matched papers (22 in last 10 years) Source
- Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
- Animal modelNot checked
Not yet enriched from Monarch / Alliance
- Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
- 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)
Not enriched in this build — Monarch phenotype joins were not run for this record.
Animal models (Monarch / Alliance)
Not enriched in this build.
Literature
Is anyone studying this?
45
45 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=5449) is 41.
45 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).
22 in the last 10 years · medium confidence · 38.6th percentile (publications denominator)
Phrase hits: 45 · MeSH hits: 1
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.
- 01Morava 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 - 02Urban 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 - 03Callewaert B3 papers · 2025
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Papers in Europe PMC - 04Gardeitchik T3 papers · 2017
Department of Pediatrics, Institute for Metabolic and Genetic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands.
Papers in Europe PMC - 05Kornak 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 - 06
- 07Mohamed M3 papers · 2017
Department of Pediatrics, Institute for Metabolic and Genetic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands.
Papers in Europe PMC - 08Albrecht B2 papers · 2011
Department of Human Genetics, University of Essen, Essen, Germany.
Papers in Europe PMC - 09Chen Y2 papers · 2026
ENT Institute, Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital, Fudan University, Shanghai, China.
Papers in Europe PMC - 10De Paepe A2 papers · 2011Papers 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 27 July 2026
No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.
medium confidence · 36.5th 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.
Where to find support
We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:
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.
"RIN2 syndrome" OR "MACS syndrome" OR "Macrocephaly-alopecia-cutis laxa-scoliosis syndrome" OR "RIN2 deficiency" OR "Tall forehead-sparse hair-skin hyperextensibility-scoliosis syndrome"
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" OR "RIN2"
Recall-expansion terms: RIN2
Study-type breakdown: 0 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase, mesh, recall-expansion; 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
Ingested 2026-07-27T09:49:12.910Z