ORPHA:324561
Hypopigmentation-punctate palmoplantar keratoderma syndrome
Also known as: Cole disease · Guttate hypopigmentation and punctate palmoplantar keratoderma · Hypopigmentation and punctate keratosis of the palms and soles
Publications
47
47.5th percentile
Trials
6
Interventional, condition-specific
Researchers
395
Distinct authors in sample
Gene link
ENPP1
Strong
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare, genetic, epidermal disease characterized by punctate keratoderma on palms and soles associated with irregularly shaped hypopigmented macules (typically localized on the extremities). Ectopic calcification (e.g. early-onset calcific tendinopathy, calcinosis cutis) and pachyonychia may be occasionally associated.
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:0014227
- OMIM:615522
- UMLS:C3809781
Additional Mondo synonyms (2)
guttate hypopigmentation and punctate palmoplantar keratoderma · hypopigmentation and punctate keratosis of the palms and soles
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
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedPresent
Strong — ENPP1
- LiteraturePresent
47 matched papers (36 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 trialPresent
6 matched on ClinicalTrials.gov (3 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 (ENPP1).
GenCC classification: Strong.
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?
47
47 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.
47 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).
36 in the last 10 years · high confidence · 47.5th percentile (publications denominator)
Phrase hits: 47 · MeSH hits: 0
Who's working on it?
395
Distinct author names in 47 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.
- 01Ferreira CR4 papers · 2024
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. ferreiracr@mail.nih.gov.
Papers in Europe PMC - 02Rutsch F4 papers · 2024
Department of General Pediatrics, Muenster University Children's Hospital, Muenster, Germany.
Papers in Europe PMC - 03Uitto J3 papers · 2022
Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: Jouni.Uitto@jefferson.edu.
Papers in Europe PMC - 04Ansh AJ2 papers · 2024
Department of Pathology, Yale University, New Haven, CT, USA.
Papers in Europe PMC - 05Braddock DT2 papers · 2024
Department of Pathology, Yale University, New Haven, CT, USA.
Papers in Europe PMC - 06Hausser I2 papers · 2016
Institute of Pathology, University Clinic Heidelberg, Heidelberg, Germany.
Papers in Europe PMC - 07Levine MA2 papers · 2022
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia and the Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Papers in Europe PMC - 08Li Q2 papers · 2022
Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Papers in Europe PMC - 09Nitschke Y2 papers · 2024
Department of General Pediatrics, Münster University Children's Hospital, 48149 Münster, Germany.
Papers in Europe PMC - 10Orlow SJ2 papers · 2013Papers in Europe PMC
Clinical research
Is a treatment being tested?
6
interventional trials for this specific condition
6 interventional trials matched this specific condition name; 3 currently recruiting in our sample.
Data as of 27 July 2026
6 interventional trials — more than 73% of diseases in the trials denominator have none at all (5114 of 7003; this disease is at the 89th percentile).
high confidence · 89th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
6 interventional trials matched after quoted-phrase search and title/condition post-filter.
- NCT05734196·RECRUITING·The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency
Conditions: Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency · Autosomal Recessive Hypophosphatemic Rickets · Generalized Arterial Calcification of Infancy · ATP-Binding Cassette Subfamily C Member 6 Deficiency·Matched via recall expansion
- NCT07473973·RECRUITING·ENERGY 2: Evaluation of the Efficacy and Safety of INZ-701 in Infants With ENPP1 Deficiency
Conditions: Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency · Autosomal Recessive Hypophosphatemic Rickets · Generalized Arterial Calcification of Infancy 1·Matched via recall expansion
- NCT06462547·RECRUITING·ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency
Conditions: Gene Mutations · Pseudoxanthoma Elasticum · Arterial Calcification · Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency·Matched via recall expansion
Observational and natural-history studies
4 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
- NCT06302439·RECRUITING·PROPEL - A Prospective Observational Patient Registry to Evaluate ENPP1 and ABCC6 Deficiency
Conditions: Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Deficiency · ATP-Binding Cassette Subfamily C Member 6 Deficiency·Matched via recall expansion
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.
"Hypopigmentation-punctate palmoplantar keratoderma syndrome" OR "Cole disease" OR "Guttate hypopigmentation and punctate palmoplantar keratoderma" OR "Hypopigmentation and punctate keratosis of the palms and soles" OR "Hypopigmentation and punctate keratosis of palms and soles"
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Hypopigmentation-punctate palmoplantar keratoderma syndrome" OR "Cole disease" OR "Guttate hypopigmentation and punctate palmoplantar keratoderma" OR "Hypopigmentation and punctate keratosis of the palms and soles" OR "Hypopigmentation and punctate keratosis of palms and soles" OR "ENPP1"
Recall-expansion terms: ENPP1
Interventional trials matched via: recall-expansion (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).
Study-type breakdown: 6 interventional · 4 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase, recall-expansion; with hits: phrase, recall-expansion
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
Ingested 2026-07-27T13:37:35.560Z