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ORPHA:300284

Connective tissue disorder due to lysyl hydroxylase-3 deficiency

low confidenceDisorder

Also known as: Bone fragility-contractures-arterial rupture-deafness syndrome · Bone fragility-contractures-arterial rupture-hearing loss syndrome · Connective tissue disorder due to LH3 deficiency

Publications

1,108

Trials

0

Interventional, condition-specific

Researchers

119

Distinct authors in sample

Gene link

PLOD3

Strong

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

Connective tissue disorder due to lysyl hydroxylase-3 deficiency is a rare, genetic disease, caused by lack of lysyl hydrohylase 3 (LH3) activity, characterized by multiple tissue and organ involvement, including skeletal abnormalities (club foot, scoliosis, osteopenia, pathologic fractures), ocular involvement (flat retinae, myopia, cataracts) and hair, nail and skin anomalies (coarse, abnormally distributed hair, skin blistering, reduced palmar creases, hypoplastic nails). Patients also present intrauterine growth retardation, facial dysmorphism (flat facial profile, low-set ears, shallow orbits, short and upturned nose, downturned corners of mouth) and joint flexion contractures. Growth and , bilateral sensorineural deafness, friable diaphragm and later-onset spontaneous vascular ruptures are additional reported features.

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 (4)

bone fragility with contractures, arterial rupture, and deafness · bone fragility-contractures-arterial rupture-deafness syndrome · connective tissue disorder due to LH3 deficiency · connective tissue disorder due to lysyl hydroxylase-3 deficiency

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.”

4/6 stages with a signal

No specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedPresent

    Strong — PLOD3

  2. LiteraturePresent

    1,108 matched papers (794 in last 10 years) Source

  3. Phenotype characterisedPresent

    39 HPO annotations (e.g. Abnormality of the dentition; Anteverted nares; Nail dysplasia) 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 trialPartial

    None under the specific name; 1 for broader category connective tissue disorder

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 (PLOD3).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

39

Associated phenotypes · MONDO:0012892

  • Abnormality of the dentition
  • Anteverted nares
  • Nail dysplasia
  • Short nose
  • J-shaped sella turcica

Showing 5 of 39 — 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?

1,108

1,108 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.

1,108 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).

794 in the last 10 years · low confidence

Phrase hits: 15 · MeSH hits: 2

Open Europe PMC search

Who's working on it?

119

Distinct author names in 15 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
    Dietz HC2 papers · 2014

    McKusick-Nathans Institute of Genetic Medicine, Departments of Pediatrics, Medicine, and Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Howard Hughes Medical Institute, Baltimore, Maryland 21205.

    Papers in Europe PMC
  2. 02
    Li F2 papers · 2022

    Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.

    Papers in Europe PMC
  3. 03
    Li L2 papers · 2023

    BGI-Wuhan Clinical Laboratory, BGI-Shenzhen, 430074, Wuhan, China.

    Papers in Europe PMC
  4. 04
    Li W2 papers · 2025

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

    Papers in Europe PMC
  5. 05
    Lindsay ME2 papers · 2014

    Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-1832, USA.

    Papers in Europe PMC
  6. 06
    Abtahi D1 paper · 2024

    Anesthesiology Department, University of Shahid Beheshti Medical Sciences, Imam Hossein Medical Center, Shahid Madani Street, Tehran, Iran. drdariushabtahi@yahoo.com.

    Papers in Europe PMC
  7. 07
    Adams JC1 paper · 2023

    School of Biochemistry, University of Bristol, Bristol, United Kingdom.

    Papers in Europe PMC
  8. 08
    Ahn YH1 paper · 2021

    Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States.

    Papers in Europe PMC
  9. 09
    Athari M1 paper · 2024

    Department of Orthopedic Surgery, University of Shahid Beheshti Medical Sciences, Shahid Madani Street, Tehran, Iran.

    Papers in Europe PMC
  10. 10
    Au L1 paper · 2013
    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). 1 trial are registered for connective tissue disorder, the broader category — shown separately because they may or may not enrol this specific subtype.

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.

1 interventional trial matched connective tissue disorder, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: connective tissue disorder

1

Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.

Worth raising with a clinician. How we count trials.

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 Connective tissue disorder due to lysyl hydroxylase-3 deficiency — 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.

("Connective tissue disorder due to lysyl hydroxylase-3 deficiency" OR "Bone fragility-contractures-arterial rupture-deafness syndrome" OR "Bone fragility-contractures-arterial rupture-hearing loss syndrome" OR "Connective tissue disorder due to LH3 deficiency" OR "bone fragility with contractures, arterial rupture, and deafness") OR (MESH:"Bone Fragility with Contractures, Arterial Rupture, and Deafness") OR ("PLOD3" OR "PLOD3 syndrome" OR "PLOD3-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Bone Fragility with Contractures, Arterial Rupture, and Deafness

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

"Connective tissue disorder due to lysyl hydroxylase-3 deficiency" OR "Bone fragility-contractures-arterial rupture-deafness syndrome" OR "Bone fragility-contractures-arterial rupture-hearing loss syndrome" OR "Connective tissue disorder due to LH3 deficiency" OR "bone fragility with contractures, arterial rupture, and deafness"

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

Parent-category trials query:

"connective tissue disorder"

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

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 (1108) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T12:38:32.866Z