ORPHA:562528
Congenital limbs-face contractures-hypotonia-developmental delay syndrome
Also known as: CLIFAHDD syndrome
Publications
1,206
Trials
1
Interventional, condition-specific
Researchers
716
Distinct authors in sample
Gene link
NALCN
Definitive
Readiness
4/6
Stages with a signal
Clinical definition (Orphanet)
A rare multiple anomalies/ syndrome with characterized by severe contractures of the limbs and face, , respiratory distress, and global . facial features include downslanting palpebral fissures, broad nasal bridge, large nares, long philtrum, and deep nasolabial folds, among others. Limb deformities (camptodactyly, clubfoot), short neck, scoliosis, as well as have also been reported. Brain MRI may show cerebral and cerebellar atrophy in some cases.
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:0014556
- OMIM:616266
- UMLS:C4225398
Additional Mondo synonyms (2)
congenital contractures of the limbs and face, hypotonia, and developmental delay · congenital limbs-face contractures-hypotonia-developmental delay 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.”
4/6 stages with a signal
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedPresent
Definitive — NALCN
- LiteraturePresent
1,206 matched papers (953 in last 10 years) Source
- Phenotype characterisedPresent
89 HPO annotations (e.g. Long philtrum; Ulnar deviation of the hand or of fingers of the hand; Flexion contracture) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialPresent
1 matched on ClinicalTrials.gov (1 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 (NALCN).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
89
Associated phenotypes · MONDO:0014556
- Long philtrum
- Ulnar deviation of the hand or of fingers of the hand
- Flexion contracture
- Talipes equinovarus
- High palate
Showing 5 of 89 — 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?
1,206
1,206 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.
1,206 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).
953 in the last 10 years · low confidence
Phrase hits: 64 · MeSH hits: 0
Who's working on it?
716
Distinct author names in 64 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.
- 01Monteil A5 papers · 2025
IGF, CNRS, INSERM, University of Montpellier, LabEx 'Ion Channel Science and Therapeutics', Montpellier, France. arnaud.monteil@igf.cnrs.fr.
Papers in Europe PMC - 02Chen Y4 papers · 2025
Department of Obstetrics and Chongqing Fetal Medical Centre, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing, 400016, People's Republic of China.
Papers in Europe PMC - 03Li Q4 papers · 2021Papers in Europe PMC
- 04Lory P4 papers · 2025
IGF, CNRS, INSERM, University of Montpellier, LabEx 'Ion Channel Science and Therapeutics', Montpellier, France.
Papers in Europe PMC - 05Yang Y4 papers · 2021
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
Papers in Europe PMC - 06Chen Q3 papers · 2025
Department of Obstetrics and Chongqing Fetal Medical Centre, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing, 400016, People's Republic of China.
Papers in Europe PMC - 07Dieterich K3 papers · 2026
INSERM U1209, Institute for Advanced Biosciences, Grenoble-Alps University Hospital, Medical Genetics, Univ. Grenoble Alpes, Grenoble, France.
Papers in Europe PMC - 08Li H3 papers · 2025
BGI-Anhui Clinical Laboratory, BGI-Shenzhen, 236000, Fuyang, China.
Papers in Europe PMC - 09Liu Y3 papers · 2025
Department of Genetics, Jiangxi Maternal and Child Health Hospital, 330006, Nanchang, China.
Papers in Europe PMC - 10Novelli A3 papers · 2025
Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome 00146, Italy.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
1
interventional trials for this specific condition
1 interventional trial matched this specific condition name; 1 currently recruiting in our sample.
Data as of 26 October 2026 · last trial check 30 September 2026
1 interventional trial — more than 77.2% of diseases in the trials denominator have none at all (5498 of 7126; this disease is at the 80.1th percentile).
low confidence · 80.1th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
1 interventional trials matched after quoted-phrase search and title/condition post-filter.
- NCT07845825·NOT YET RECRUITING·Aprepitant for the Treatment of CLIFAHDD
Conditions: CLIFAHDD · Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay · NALCN Channelopathy · Ataxia - Other·Matched via name phrase
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 2 · after dedupe 2 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 2 · 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 (2)
- ctis·2024-516263-92-00·Expired·A Phase 3, Randomized, Open-Label, Multicenter Study to Evaluate the Safety (Compared to Iron Sucrose), Efficacy and Pharmacokinetics of Ferumoxytol for the Treatment of Iron Deficiency Anemia (IDA) in Pediatrics Subjects with Chronic Kidney Disease (CKD)
skipped — LLM skipped (--skip-llm)
- ctis·2022-500197-34-01·Authorised, ongoing·A Phase II double-blind multi-center, placebo-controlled trial, to assess the efficacy and safety of alpelisib (BYL719) in pediatric and adult patients with Megalencephaly-CApillary malformation Polymicrogyria syndrome (MCAP)
skipped — LLM skipped (--skip-llm)
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 Congenital limbs-face contractures-hypotonia-developmental delay syndrome — check Associations / patient organisations on that page.
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.
("Congenital limbs-face contractures-hypotonia-developmental delay syndrome" OR "CLIFAHDD syndrome" OR "congenital contractures of the limbs and face, hypotonia, and developmental delay" OR "congenital contractures of limbs and face, hypotonia, and developmental delay") OR ("NALCN" OR "NALCN syndrome" OR "NALCN-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Congenital limbs-face contractures-hypotonia-developmental delay syndrome" OR "CLIFAHDD syndrome" OR "congenital contractures of the limbs and face, hypotonia, and developmental delay" OR "congenital contractures of limbs and face, hypotonia, and developmental delay"
Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).
Study-type breakdown: 1 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase; with hits: phrase
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 (1206) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-27T18:20:26.753Z