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ORPHA:371364

Hypotonia-speech impairment-severe cognitive delay syndrome

low confidenceDisorder

Also known as: Infantile hypotonia-psychomotor retardation-characteristic facies syndrome · IHPRF syndrome

Publications

1,226

Trials

0

Interventional, condition-specific

Researchers

638

Distinct authors in sample

Gene link

NALCN

Strong

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

-speech impairment-severe cognitive delay syndrome is a rare, genetic neurodegenerative disorder characterized by severe, persistent (presenting at birth or in early infancy), severe global (with poor or absent speech, difficulty or inability to roll, sit or walk), profound , and . Additional manifestations include microcephaly, peripheral spasticity, bilateral strabismus and nystagmus, constipation, and variable facial features (including plagiocephaly, broad forehead, small nose, low-set ears, micrognathia and open mouth with tented upper lip).

How rare: How common this is has not been clearly measured.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (4)

IHPRF · hypotonia, infantile, with psychomotor retardation and characteristic facies · hypotonia-speech impairment-severe cognitive delay syndrome · infantile hypotonia-psychomotor retardation-characteristic facies 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

    Strong — NALCN

  2. LiteraturePresent

    1,226 matched papers (972 in last 10 years) Source

  3. Phenotype characterisedPresent

    329 HPO annotations (e.g. Fetal pyelectasis; Corneal opacity; Nystagmus) 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 (NALCN).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

329

Associated phenotypes · MONDO:0014176

  • Fetal pyelectasis
  • Corneal opacity
  • Nystagmus
  • Microcephaly
  • Low-set ears

Showing 5 of 329 — 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?

1,226

1,226 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.

1,226 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).

972 in the last 10 years · low confidence

Phrase hits: 55 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

638

Distinct author names in 55 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
    Monteil A4 papers · 2025

    Institut de Génomique Fonctionnelle, CNRS UMR 5203, Universités Montpellier 1&2 Montpellier, France ; INSERM, U 661 Montpellier, France ; LabEx 'Ion Channel Science and Therapeutics' Montpellier, France.

    Papers in Europe PMC
  2. 02
    Liu Y3 papers · 2025

    Department of Genetics, Jiangxi Maternal and Child Health Hospital, 330006, Nanchang, China.

    Papers in Europe PMC
  3. 03
    Lory P3 papers · 2019

    Institut de Génomique Fonctionnelle, CNRS UMR 5203, Universités Montpellier 1&2 Montpellier, France ; INSERM, U 661 Montpellier, France ; LabEx 'Ion Channel Science and Therapeutics' Montpellier, France.

    Papers in Europe PMC
  4. 04
    Bayrak-Toydemir P2 papers · 2025

    From the Department of Biology and Howard Hughes Medical Institute (E.G.B., E.M.J.), and Department of Pathology (Y.S., P.B.-T.), University of Utah, Salt Lake City; ARUP Institute for Clinical and Experimental Pathology (Y.S., P.B.-T.), Salt Lake City, UT; Division of Medical Genetics (D.A.S.), Department of Pediatrics, Stanford University, CA; Department of Neurology (T.M.N.), Pediatric Motor Disorders Research Program, University of Utah School of Medicine, Salt Lake City; and Department of Neurology (K.J.S.), Massachusetts General Hospital, Boston.

    Papers in Europe PMC
  5. 05
    Bhat V2 papers · 2024

    Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.

    Papers in Europe PMC
  6. 06
    Bruel AL2 papers · 2022

    INSERM U1231, LNC UMR1231 GAD, Burgundy University, 21079 Dijon, France.

    Papers in Europe PMC
  7. 07
    Carey JC2 papers · 2025

    Department of Pediatrics, University of Utah, Salt Lake City, UT 84108, USA.

    Papers in Europe PMC
  8. 08
    Chen L2 papers · 2022

    State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, 100871, Beijing, China. chenlei2016@pku.edu.cn.

    Papers in Europe PMC
  9. 09
    Cogné B2 papers · 2022

    Department of Medical Genetics, CHU Nantes, 44093 Nantes, France; l'Institut du Thorax, INSERM, CNRS, UNIV Nantes, 44007 Nantes, France.

    Papers in Europe PMC
  10. 10
    Faivre L2 papers · 2022

    INSERM U1231, LNC UMR1231 GAD, Burgundy University, 21079 Dijon, France; Reference Center for Developmental Anomalies, Department of Medical Genetics, Dijon University Hospital, 21000 Dijon, France.

    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).

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.

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 Hypotonia-speech impairment-severe cognitive delay 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.

("Hypotonia-speech impairment-severe cognitive delay syndrome" OR "Infantile hypotonia-psychomotor retardation-characteristic facies syndrome" OR "IHPRF syndrome" OR "IHPRF" OR "hypotonia, infantile, with psychomotor retardation and characteristic facies") OR ("NALCN" OR "NALCN syndrome" OR "NALCN-related")

Run this search on Europe PMC

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

"Hypotonia-speech impairment-severe cognitive delay syndrome" OR "Infantile hypotonia-psychomotor retardation-characteristic facies syndrome" OR "IHPRF syndrome" OR "IHPRF" OR "hypotonia, infantile, with psychomotor retardation and characteristic facies"

Study-type breakdown: 0 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 (1226) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-27T14:59:47.812Z