Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (710 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A condition with congenital and acquired forms causing recurrent ulcers in the fingers and toes. The congenital form exhibits autosomal dominant inheritance; the acquired form is found in workers who handle vinyl chloride. When acro-osteolysis is accompanied by generalized osteoporosis and skull deformations, it is called hajdu-cheney syndrome.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Acro Osteolysis; Acro-Osteolysis Syndromes; Acro-Osteolysis Syndrome; Acroosteolysis; Acroosteolysis Syndrome.
Where it fits in the MeSH classification
- Broader topics
- Bone Diseases, Developmental; Osteolysis
- Narrower topics
- Hajdu-Cheney Syndrome
- See also
- Osteolysis, Essential
Related concepts
- Vinyl Chloride
- Osteoporosis
- Hajdu-Cheney Syndrome
Research landscape
PubMed indexes 325 records tagged with the MeSH heading “Acro-Osteolysis” (counts retrieved 2026-11-04). 80 of them (24.6%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 145 records.
Reviews account for 38 records (11.7%) and meta-analyses for 1. Randomized controlled trials number 0 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 39 |
| 2000-2009 | 61 |
| 2010-2019 | 145 |
| 2020 onward | 80 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 38 | 11.7% |
| Meta-analyses | 1 | 0.3% |
| Randomized controlled trials | 0 | 0.0% |
Method: PubMed query "Acro-Osteolysis"[MeSH Terms] with publication-type and date filters, retrieved 2026-11-04.
Reading the evidence in bones, joints, muscles and skin
Joint, bone, muscle and skin conditions are often judged by pain scores, function questionnaires, imaging or photographs, and symptoms can fluctuate, so placebo response and natural improvement matter. Imaging changes are common in people without symptoms. Nothing on this page is advice about treatment. Check how outcomes were measured, whether the comparison group received a placebo or usual care, and how long the benefit lasted.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Hajdu-Cheney syndrome: a review | 2014 | Review article Design not recorded in structured metadata | 69 | cc by PMID 25491639 · DOI · PMC4269900 |
| Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology | 2020 | Research article Design not recorded in structured metadata | 61 | cc by PMID 32917887 · DOI · PMC7486921 |
| Hajdu-Cheney Syndrome: A Systematic Review of the Literature | 2020 | Systematic review Design not recorded in structured metadata | 26 | cc by PMID 32854429 · DOI · PMC7504254 |
| Life expectancy and causes of death in classical laminopathic progeroid syndromes: systematic review with individual-patient data synthesis | 2026 | Systematic review Design not recorded in structured metadata | 0 | cc by PMID 42329128 · DOI · PMC13632853 |
Hajdu-Cheney syndrome: a review [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Hajdu Cheney Syndrome (HCS), Orpha 955, is a rare disease characterized by acroosteolysis, severe osteoporosis, short stature, specific craniofacial features, wormian bones, neurological symptoms, cardiovascular defects and polycystic kidneys.
- Closing excerpt
- In conclusion, Notch regulates skeletal development and bone remodeling, and gain-of-function mutations of NOTCH2 are associated with HCS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (194 words)
Hajdu Cheney Syndrome (HCS), Orpha 955, is a rare disease characterized by acroosteolysis, severe osteoporosis, short stature, specific craniofacial features, wormian bones, neurological symptoms, cardiovascular defects and polycystic kidneys. HCS is rare and is inherited as autosomal dominant although many sporadic cases have been reported. HCS is associated with mutations in exon 34 of NOTCH2 upstream the PEST domain that lead to the creation of a truncated and stable NOTCH2 protein with enhanced NOTCH2 signaling activity. Although the number of cases with NOTCH2 mutations reported are limited, it would seem that the diagnosis of HCS can be established by sequence analysis of exon 34 of NOTCH2. Notch receptors are single-pass transmembrane proteins that determine cell fate, and play a critical role in skeletal development and homeostasis. Dysregulation of Notch signaling is associated with skeletal developmental disorders. There is limited information about the mechanisms of the bone loss and acroosteolysis in HCS making decisions regarding therapeutic intervention difficult. Bone antiresorptive and anabolic agents have been tried to treat the osteoporosis, but their benefit has not been established. In conclusion, Notch regulates skeletal development and bone remodeling, and gain-of-function mutations of NOTCH2 are associated with HCS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 25491639 · DOI · PMC4269900
Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Mandibuloacral dysplasia syndromes are mainly due to recessive LMNA or ZMPSTE24 mutations, with cardinal nuclear morphological abnormalities and dysfunction.
- Closing excerpt
- We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Mandibuloacral dysplasia syndromes are mainly due to recessive LMNA or ZMPSTE24 mutations, with cardinal nuclear morphological abnormalities and dysfunction. We report five homozygous null mutations in MTX2, encoding Metaxin-2 (MTX2), an outer mitochondrial membrane protein, in patients presenting with a severe laminopathy-like mandibuloacral dysplasia characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis and severe hypertension. Loss of MTX2 in patients' primary fibroblasts leads to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts are resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Interestingly, secondary nuclear morphological defects are observed in both MTX2-mutant fibroblasts and mtx-2-depleted C. elegans. We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32917887 · DOI · PMC7486921
Hajdu-Cheney Syndrome: A Systematic Review of the Literature [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Hajdu-Cheney syndrome (HCS) is a rare genetic disease that causes acroosteolysis and generalized osteoporosis, accompanied by a series of developmental skeletal disorders and multiple clinical and radiological manifestations.
- Closing excerpt
- Finally, 76 articles were included, and after their analysis, we have obtained a series of hypotheses as results that will support further studies on this matter.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (185 words)
Hajdu-Cheney syndrome (HCS) is a rare genetic disease that causes acroosteolysis and generalized osteoporosis, accompanied by a series of developmental skeletal disorders and multiple clinical and radiological manifestations. It has an autosomal dominant inheritance, although there are several sporadic non-hereditary cases. The gene that has been associated with Hajdu-Cheney syndrome is NOTCH2. The described phenotype and clinical signs and symptoms are many, varied, and evolve over time. As few as 50 cases of this disease, for which there is currently no curative treatment, have been reported to date. The main objective of this systematic review was to evaluate the results obtained in research regarding Hajdu-Cheney Syndrome. The findings are reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and were registered on the web PROSPERO under the registration number CRD42020164377. A bibliographic search was carried out using the online databases Orphanet, PubMed, and Scielo; articles from other open access sources were also considered. Finally, 76 articles were included, and after their analysis, we have obtained a series of hypotheses as results that will support further studies on this matter.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32854429 · DOI · PMC7504254
Life expectancy and causes of death in classical laminopathic progeroid syndromes: systematic review with individual-patient data synthesis [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Classical laminopathic progeroid syndromes link nuclear-envelope defects to accelerated aging, but the specific prognosis for each subtype remains unclear.
- Closing excerpt
- In sum, survival and mortality patterns differ markedly across classical laminopathic progeria; genetically confirmed IPD resolved by subtype provides more reliable estimates for clinical counseling and trial design in ultra-rare progeroid disorders.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (181 words)
Classical laminopathic progeroid syndromes link nuclear-envelope defects to accelerated aging, but the specific prognosis for each subtype remains unclear. We conducted a PRISMA-guided systematic review and individual-patient data (IPD) synthesis (PROSPERO CRD420251080312; PubMed/Scopus to 16 July 2025). Genetically confirmed IPD constituted the primary cohort; causes of death were harmonized a priori and survival assessed by Kaplan-Meier with log-rank tests. We included 169 studies and two institutional cases, previously illustrated in the literature but not comprehensively characterized, yielding 158 genetically confirmed IPD (61 deaths, 97 censored). Median survival (years, 95% CI) was: HGPS 16.0 (13.42-19.0; n=60), MAD-B 37.0 (24-44; n=21), RD-LMNA 0.92 (0.096-2.50; n=8), and RD-ZMPSTE24 0.03 (0.014-0.047; n=38); MAD-A had no deaths (n=31). Cause-of-death profiles were subtype-specific: respiratory failure predominated in RD (36/45 deaths), cardiovascular causes in HGPS (6/11), and renal complications in MAD-B (4/5). Findings were robust in sensitivity analyses (including clinical cases, risk-of-bias exclusions, and center-specific checks). In sum, survival and mortality patterns differ markedly across classical laminopathic progeria; genetically confirmed IPD resolved by subtype provides more reliable estimates for clinical counseling and trial design in ultra-rare progeroid disorders.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42329128 · DOI · PMC13632853
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Particle disease: biologic mechanisms of periprosthetic osteolysis in total hip arthroplasty [5]
- Research article Mandibuloacral dysplasia: A premature ageing disease with aspects of physiological ageing [6]
- Research article Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations [7]
- Research article Clinical and experimental aspects of notch receptor signaling: Hajdu-Cheney syndrome and related disorders [8]
- Research article Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review [9]
- Research article Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling [10]
References
- Canalis E, Zanotti S. Hajdu-Cheney syndrome: a review. . 2014. PMID 25491639 · DOI · PMC4269900
- Elouej S, Harhouri K, Le Mao M, Baujat G, Nampoothiri S, Kayserili H, et al.. Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology. . 2020. PMID 32917887 · DOI · PMC7486921
- Cortés-Martín J, Díaz-Rodríguez L, Piqueras-Sola B, Rodríguez-Blanque R, Bermejo-Fernández A, Sánchez-García JC. Hajdu-Cheney Syndrome: A Systematic Review of the Literature. . 2020. PMID 32854429 · DOI · PMC7504254
- López-Vila C, García-Cordeiro M, Estévez-Martínez L, Díaz-López EJ, Prado-Moraña T, Fernández-Pombo A, et al.. Life expectancy and causes of death in classical laminopathic progeroid syndromes: systematic review with individual-patient data synthesis. . 2026. PMID 42329128 · DOI · PMC13632853
- Gallo J, Goodman SB, Konttinen YT, Raska M. Particle disease: biologic mechanisms of periprosthetic osteolysis in total hip arthroplasty. Innate Immun. 2013. PMID 22751380 · DOI · PMC3712274
- Cenni V, D'Apice MR, Garagnani P, Columbaro M, Novelli G, Franceschi C, et al.. Mandibuloacral dysplasia: A premature ageing disease with aspects of physiological ageing. Ageing Res Rev. 2018. PMID 29208544 · DOI
- Canalis E, Zanotti S. Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations. Curr Osteoporos Rep. 2016. PMID 27241678 · DOI · PMC4927394
- Canalis E. Clinical and experimental aspects of notch receptor signaling: Hajdu-Cheney syndrome and related disorders. Metabolism. 2018. PMID 28941602 · DOI · PMC5818282
- Castberg FC, Kjaergaard S, Mosig RA, Lobl M, Martignetti C, Martignetti JA, et al.. Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review. Eur J Pediatr. 2013. PMID 23900523 · DOI
- de Vos IJHM, Wong ASW, Welting TJM, Coull BJ, van Steensel MAM. Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling. Am J Med Genet A. 2019. PMID 31218820 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.