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 (703 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 congenital abnormality in which the cerebrum is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
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: Microcephalies; Microlissencephaly; Microlissencephalies; Severe Congenital Microcephaly; Congenital Microcephalies, Severe; Congenital Microcephaly, Severe; Microcephalies, Severe Congenital; Microcephaly, Severe Congenital.
Where it fits in the MeSH classification
- Broader topics
- Craniofacial Abnormalities; Malformations of Cortical Development, Group I
- Narrower topics
- Porencephaly
Related concepts
- Cerebrum
Research landscape
PubMed indexes 7,006 records tagged with the MeSH heading “Microcephaly” (counts retrieved 2026-10-29). 1,651 of them (23.6%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 2,382 records.
Reviews account for 845 records (12.1%) and meta-analyses for 11. Randomized controlled trials number 4 (0.1%) 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 | 2,144 |
| 2000-2009 | 829 |
| 2010-2019 | 2,382 |
| 2020 onward | 1,651 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 845 | 12.1% |
| Meta-analyses | 11 | 0.2% |
| Randomized controlled trials | 4 | 0.1% |
Method: PubMed query "Microcephaly"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
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 |
|---|---|---|---|---|
| Pathogenesis of Zika Virus Infection | 2023 | Review article Design not recorded in structured metadata | 72 | cc by PMID 36151059 · DOI · PMC10893765 |
| Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy | 2022 | Research article Design not recorded in structured metadata | 42 | cc by PMID 36333305 · DOI · PMC9636423 |
| Zika Virus Neuropathogenesis: The Different Brain Cells, Host Factors and Mechanisms Involved | 2022 | Review article Design not recorded in structured metadata | 41 | cc by PMID 35371036 · DOI · PMC8966389 |
| Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders | 2026 | Research article Design not recorded in structured metadata | 12 | cc by PMID 41951737 · DOI · PMC13253345 |
Pathogenesis of Zika Virus Infection [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Zika virus (ZIKV) is an emerging virus from the Flaviviridae family that is transmitted to humans by mosquito vectors and represents an important health problem.
- Closing excerpt
- We discuss recent reports on the mechanisms used by ZIKV to replicate efficiently, and we highlight potential new areas of research for the development of therapeutic approaches.
- 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)
Zika virus (ZIKV) is an emerging virus from the Flaviviridae family that is transmitted to humans by mosquito vectors and represents an important health problem. Infections in pregnant women are of major concern because of potential devastating consequences during pregnancy and have been associated with microcephaly in newborns. ZIKV has a unique ability to use the host machinery to promote viral replication in a tissue-specific manner, resulting in characteristic pathological disorders. Recent studies have proposed that the host ubiquitin system acts as a major determinant of ZIKV tropism by providing the virus with an enhanced ability to enter new cells. In addition, ZIKV has developed mechanisms to evade the host immune response, thereby allowing the establishment of viral persistence and enhancing viral pathogenesis. We discuss recent reports on the mechanisms used by ZIKV to replicate efficiently, and we highlight potential new areas of research for the development of therapeutic approaches.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36151059 · DOI · PMC10893765
Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation.
- Closing excerpt
- Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability.
- 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 (155 words)
Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36333305 · DOI · PMC9636423
Zika Virus Neuropathogenesis: The Different Brain Cells, Host Factors and Mechanisms Involved [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Zika virus (ZIKV), despite being discovered six decades earlier, became a major health concern only after an epidemic in French Polynesia and an increase in the number of microcephaly cases in Brazil.
- Closing excerpt
- Overall, it covers key components for understanding the crosstalk between ZIKV and the brain.
- 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 (186 words)
Zika virus (ZIKV), despite being discovered six decades earlier, became a major health concern only after an epidemic in French Polynesia and an increase in the number of microcephaly cases in Brazil. Substantial evidence has been found to support the link between ZIKV and neurological complications in infants. The virus targets various cells in the brain, including radial glial cells, neural progenitor cells (NPCs), astrocytes, microglial and glioblastoma stem cells. It affects the brain cells by exploiting different mechanisms, mainly through apoptosis and cell cycle dysregulation. The modulation of host immune response and the inflammatory process has also been demonstrated to play a critical role in ZIKV induced neurological complications. In addition to that, different ZIKV strains have exhibited specific neurotropism and unique molecular mechanisms. This review provides a comprehensive and up-to-date overview of ZIKV-induced neuroimmunopathogenesis by dissecting its main target cells in the brain, and the underlying cellular and molecular mechanisms. We highlighted the roles of the different ZIKV host factors and how they exploit specific host factors through various mechanisms. Overall, it covers key components for understanding the crosstalk between ZIKV and the brain.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35371036 · DOI · PMC8966389
Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Recently, de novo variants in an 18-nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder that is predicted to affect tens of thousands of individuals worldwide1,2.
- Closing excerpt
- Together, this work defines the landscape of variant function across RNU4-2, providing critical insights for both diagnosis and therapeutic development.
- 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 (212 words)
Recently, de novo variants in an 18-nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder that is predicted to affect tens of thousands of individuals worldwide1,2. RNU4-2 is a non-protein-coding gene that is transcribed into the U4 small nuclear RNA component of the major spliceosome3. ReNU syndrome variants disrupt spliceosome function and alter 5' splice site selection1,4. Here we performed saturation genome editing (SGE) of RNU4-2 to identify the functional and clinical impact of variants across the entire gene. The resulting SGE function scores, derived from variants' effects on cell fitness, discriminate ReNU syndrome variants from those observed in the population and markedly outperform in silico variant effect prediction. Using these data, we redefine the ReNU syndrome critical region at single-nucleotide resolution, resolve variant pathogenicity for variants of uncertain significance and show that SGE function scores delineate variants by phenotypic severity and the extent of observed splicing disruption. Furthermore, we identify variants affecting function in regions of RNU4-2 that are critical for interactions with other spliceosome components. We show that these variants cause a new recessive neurodevelopmental disorder that is distinct from ReNU syndrome. Together, this work defines the landscape of variant function across RNU4-2, providing critical insights for both diagnosis and therapeutic development.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41951737 · DOI · PMC13253345
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 Primary microcephaly: do all roads lead to Rome? [5]
- Research article Centrosomes and cilia in human disease [6]
- Research article Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings [7]
- Research article Assessing the global threat from Zika virus [8]
- Research article Human cerebral organoids - a new tool for clinical neurology research [9]
- Research article The Genetics of Primary Microcephaly [10]
References
- Giraldo MI, Gonzalez-Orozco M, Rajsbaum R. Pathogenesis of Zika Virus Infection. . 2023. PMID 36151059 · DOI · PMC10893765
- Grange LJ, Reynolds JJ, Ullah F, Isidor B, Shearer RF, Latypova X, et al.. Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy. . 2022. PMID 36333305 · DOI · PMC9636423
- Komarasamy TV, Adnan NAA, James W, Balasubramaniam VRMT. Zika Virus Neuropathogenesis: The Different Brain Cells, Host Factors and Mechanisms Involved. . 2022. PMID 35371036 · DOI · PMC8966389
- De Jonghe J, Kim HC, Adedeji A, Leitão E, Dawes R, Kajba CM, et al.. Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders. . 2026. PMID 41951737 · DOI · PMC13253345
- Thornton GK, Woods CG. Primary microcephaly: do all roads lead to Rome?. Trends Genet. 2009. PMID 19850369 · DOI · PMC2816178
- Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G, Godinho SA. Centrosomes and cilia in human disease. Trends Genet. 2011. PMID 21680046 · DOI · PMC3144269
- Woods CG, Bond J, Enard W. Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet. 2005. PMID 15806441 · DOI · PMC1199363
- Lessler J, Chaisson LH, Kucirka LM, Bi Q, Grantz K, Salje H, et al.. Assessing the global threat from Zika virus. Science. 2016. PMID 27417495 · DOI · PMC5467639
- Eichmüller OL, Knoblich JA. Human cerebral organoids - a new tool for clinical neurology research. Nat Rev Neurol. 2022. PMID 36253568 · DOI · PMC9576133
- Jayaraman D, Bae BI, Walsh CA. The Genetics of Primary Microcephaly. Annu Rev Genomics Hum Genet. 2018. PMID 29799801 · 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 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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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.