{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:05:26Z","timestamp":1792296326620,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T00:00:00Z","timestamp":1496966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Microcephaly is defined as a head circumference more than two standard deviations below the mean for gender and age. Congenital microcephaly is present at birth, whereas postnatal microcephaly occurs later in life. Genetic abnormalities, syndromes, metabolic disorders, teratogens, infections, prenatal, perinatal, and postnatal injuries can cause both congenital and postnatal microcephaly. Evaluation of patients with microcephaly begins with a thorough history and physical examination. In cases of worsening microcephaly or neurological signs or symptoms, neuroimaging, metabolic, or genetic testing should be strongly considered. Any further studies and workup should be directed by the presence of signs or symptoms pointing to an underlying diagnosis and are usually used as confirmatory testing for certain conditions. Neuroimaging with magnetic resonance imaging (MRI) is often the first diagnostic test in evaluating children with microcephaly. Genetic testing is becoming more common and is often the next step following neuroimaging when there is no specific evidence in the history or physical examination suggesting a diagnosis. Microcephaly is a lifelong condition with no known cure. The prognosis is usually worse for children who experienced an intrauterine infection or have a chromosomal or metabolic abnormality. Zika virus has rapidly spread since 2015, and maternal infection with this virus is associated with microcephaly and other serious brain abnormalities. Microcephaly has become much more prevalent in the news and scientific community with the recent emergence of Zika virus as a cause of congenital microcephaly.<\/jats:p>","DOI":"10.3390\/children4060047","type":"journal-article","created":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T10:29:59Z","timestamp":1497004199000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Microcephaly"],"prefix":"10.3390","volume":"4","author":[{"given":"Emily","family":"Hanzlik","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University School of Medicine, 8161 Doctors\u2019 Office Tower, 2200 Children\u2019s Way, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Gigante","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University School of Medicine, 8161 Doctors\u2019 Office Tower, 2200 Children\u2019s Way, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.spen.2007.07.003","article-title":"Microcephaly Syndromes","volume":"14","author":"Abuelo","year":"2007","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_2","first-page":"e1","article-title":"Prenatal head growth and child neuropsychological development at age 14 months","volume":"212","author":"Sunyer","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ashwal, S., Michelson, D., Plauner, L., and Dobyns, W.B. (2009). Practice Parameter: Evaluation of the Child with Microcephaly (An Evidence-Based Review), American Academy of Neurology.","DOI":"10.1212\/WNL.0b013e3181b783f7"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/uog.7556","article-title":"Developmental outcome of isolated fetal microcephaly","volume":"36","author":"Lev","year":"2010","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/dmcn.12425","article-title":"Diagnostic approach to microcephaly in childhood: A two-center study and review of the literature","volume":"56","author":"Pivarcsi","year":"2014","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1542\/peds.2008-2784","article-title":"Acquired Microcephaly: Causes, Patterns, Motor and IQ Effects, and Associated Growth Changes","volume":"124","author":"Baxter","year":"2009","journal-title":"Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/ajmg.c.31397","article-title":"Congenital Microcephaly","volume":"166","author":"Alcantara","year":"2014","journal-title":"Am. J. Med. Genet. Part C"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1067\/mob.2003.452","article-title":"Microcephaly: An epidemiolgic analysis","volume":"188","author":"Krauss","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_9","first-page":"1","article-title":"Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly","volume":"9","author":"Rump","year":"2016","journal-title":"BMC Med. Genom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.conb.2004.01.003","article-title":"Human microcephaly","volume":"14","author":"Woods","year":"2004","journal-title":"Curr. Opin. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"National Birth Defects Prevention Network (2013). Major birth defects data from population-based birth defects surveillance programs in the United States, 2006\u20132010. Birth Defects Res. Part A, 97, S1\u2013S172.","DOI":"10.1002\/bdra.23198"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/wdev.89","article-title":"Genetic causes of microcephaly and lessons for neuronal development","volume":"2","author":"Gilmore","year":"2013","journal-title":"Wiley Interdisip. Rev. Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"391","DOI":"10.5144\/0256-4947.2016.391","article-title":"A novel splice-site mutation in the ASPM gene underlies autosomal recessive microcephaly","volume":"36","author":"Hashmi","year":"2016","journal-title":"Ann. Saudi Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.tig.2009.09.011","article-title":"Primary microcephaly: Do all roads lead to Rome?","volume":"25","author":"Thornton","year":"2009","journal-title":"Trends Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Doobin, D.J., Kemal, S., Dantas, T.J., and Vallee, R.B. (2016). Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages. Nat. Commun., 7.","DOI":"10.1038\/ncomms12551"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"a000455","DOI":"10.1101\/mcs.a000455","article-title":"De novo POGZ mutations are associated with neurodevelopmental disorders and microcephaly","volume":"1","author":"Ye","year":"2015","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kadir, R., Harel, T., Markus, B., Perez, Y., Bakhrat, A., Cohen, I., Volodarsky, M., Feintsein-Linial, M., Chervinski, E., and Zlotogora, J. (2016). ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size. PLoS ONE, 12.","DOI":"10.1371\/journal.pgen.1005919"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Faheem, M., Naseer, M.I., Rasool, M., Chaudhary, A.G., Kumosani, T.A., Ilyas, A.M., Pushparaj, M.R., Ahmed, F., Algahtani, H.A., and Al-Qahtani, M.H. (2015). Molecular genetics of human primary microcephaly: An overview. BMC Med. Genom., 1.","DOI":"10.1186\/1755-8794-8-S1-S4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1007\/s00439-016-1724-0","article-title":"CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly","volume":"135","author":"Basit","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.yapd.2005.04.003","article-title":"Nonsyndromic microcephaly: An overview","volume":"52","author":"Leroy","year":"2005","journal-title":"Adv. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/00004703-200002000-00003","article-title":"Neurodevelopmental and neuroimaging correlates in nonsyndromal microcephalic children","volume":"21","author":"Custer","year":"2000","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1055\/s-2008-1071504","article-title":"MRI of the head in the evaluation of microcephaly","volume":"24","author":"Sugimoto","year":"1993","journal-title":"Neuropediatrics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1212\/01.WNL.0000031431.81555.16","article-title":"Practice parameter: Evaluation of the child with global developmental delay: Report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society","volume":"60","author":"Michelson","year":"2003","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1046\/j.1469-0705.2000.00092.x","article-title":"Congenital microcephaly detected by prenatal ultrasound: Genetic aspects and clinical significance","volume":"15","author":"Wessels","year":"2000","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_25","first-page":"106","article-title":"Microcephalus as the reason for visiting a regional referral neuropaediatric service","volume":"38","author":"Rebage","year":"2004","journal-title":"Rev. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/ajo.12408","article-title":"Congenital cytomegalovirus infection in pregnancy: A review of prevalence, clinical features, diagnosis, and prevention","volume":"56","author":"Naing","year":"2016","journal-title":"Aust. N. Z. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1067\/mpd.2001.112061","article-title":"Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection","volume":"138","author":"Noyola","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"870","DOI":"10.15585\/mmwr.mm6533e2","article-title":"Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection - United States, August 2016","volume":"65","author":"Russell","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Souza, B.S.F., Sampaio, G.L.A., Pereira, C.S., Campos, G.S., Sardi, S.I., Freitas, L.A.R., Figueira, C.P., Paredes, B.D., Nonaka, C.K.V., and Azevedo, C.M. (2016). Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells. Sci. Rep.","DOI":"10.1038\/srep39775"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"160231","DOI":"10.1098\/rsob.160231","article-title":"Zika virus causes supernumerary foci with centriolar proteins and impaired spindle positioning","volume":"7","author":"Wolf","year":"2017","journal-title":"Open Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Shimada, M., Matsuzaki, F., Kato, A., Kobayashi, J., Matsumoto, T., and Komatsu, K. (2016). Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158236"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1242\/dev.143768","article-title":"Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage","volume":"143","author":"Shao","year":"2016","journal-title":"Development"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Soares de Ara\u00fajo, J.S., Regis, C.T., Gomes, R.G.S., Tavares, T.R., Rocha dos Santos, C., Assuncao, P.M., N\u00f3brega, R.V., Alves Pinto, D.d.F., Bezerra, B.V.D., and da Silva Mattos, S. (2016). Microcephaly in north-east Brazil: A retrospective study on neonates born between 2012 and 2015. Bull. World Health Organ.","DOI":"10.2471\/BLT.16.170639"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rasmussen, S.A., Jamieson, D.J., Honein, M.A., and Peterson, L.R. (2016). Zika virus and birth defects\u2014Reviewing the evidence for causality. 374, 1981\u20131987.","DOI":"10.1056\/NEJMsr1604338"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature21428","article-title":"Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination","volume":"543","author":"Pardi","year":"2017","journal-title":"Nature"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/4\/6\/47\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:38:28Z","timestamp":1760207908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/4\/6\/47"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,9]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6]]}},"alternative-id":["children4060047"],"URL":"https:\/\/doi.org\/10.3390\/children4060047","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,9]]}}}