Editing Microcephaly

{{Short description|Condition in which the head is small due to an underdeveloped brain}}
{{Redirect|Microcephalus|the genus of beetle|Microcephalus (beetle)|the genus of spider|Argyrodes}}
{{Infobox medical condition (new)
| name          = Microcephaly
| synonyms      =
| image         = Microcephaly-comparison-500px.jpg
| caption       = A  baby with microcephaly (left) compared to a baby with a typical head size
| pronounce     = {{IPAc-en|,|m|ai|k|r|ou|'|s|E|f|@|l|i:}}
| field         = [[Medical genetics]], [[Psychiatry]], [[Neurology]]
| symptoms      = Abnormally small head and brain, neurological impairments
| complications = Neurological impairments
| onset         = Congenital
| duration      = Lifelong
| types         =
| causes        = Usually genetic or toxin exposure during pregnancy
| risks         =
| diagnosis     =
| differential  =
| prevention    = Avoiding [[alcohol consumption while pregnant]]
| treatment     =
| medication    =
| prognosis     =
| frequency     = 2–12 per 10,000 births<ref>{{cite web |title=Microcephaly |date=April 2023 |work=Health Library: Diseases & Conditions |publisher=Cleveland Clinic |url=https://my.clevelandclinic.org/health/diseases/9843-microcephaly }}</ref>
| deaths        =
}}
<!-- Definition and symptoms -->
[[File:Hold Me Mother, 2018 - Wellcome Photography Prize 2019.jpg|thumb|A mother holding her son who was born with microcephaly due to [[vertically transmitted infection]] with [[Zika virus]]]]
'''Microcephaly''' (from [[Neo-Latin]] ''microcephalia'', from [[Ancient Greek]] μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head"<ref>{{cite web|url=http://www.merriam-webster.com/dictionary/microcephaly|title=Microcephaly - Definition of Microcephaly by Merriam-Webster|url-status=live|archive-url=https://web.archive.org/web/20140914001123/http://www.merriam-webster.com/dictionary/microcephaly|archive-date=2014-09-14}}</ref>) is a medical condition involving a smaller-than-normal [[head]].<ref name=NIH2015>{{cite web|title=NINDS Microcephaly Information Page|url=http://www.ninds.nih.gov/disorders/Microcephaly/microcephaly.htm|website=NINDS|access-date=11 March 2016|date=June 30, 2015|url-status=dead|archive-url=https://web.archive.org/web/20160311132503/http://www.ninds.nih.gov/disorders/Microcephaly/microcephaly.htm|archive-date=2016-03-11}}</ref> Microcephaly may be [[congenital|present at birth]] or it may develop in the first few years of life.<ref name=NIH2015/>  [[Brain]] development is often affected; people with this disorder often have an [[intellectual disability]], poor motor function, poor speech, abnormal facial features, [[seizures]] and [[dwarfism]].<ref name=NIH2015/>

<!-- Cause and diagnosis -->
The disorder is caused by a disruption to the genetic processes that [[Development of the nervous system in humans|form the brain]] early in pregnancy,<ref name="NIH2015" /> though the cause is not identified in most cases.<ref name="CDC" /> Many [[genetic syndromes]] can result in microcephaly, including [[Chromosome abnormality|chromosomal]] and [[Single-gene disorder|single-gene]] conditions, though almost always in combination with other symptoms. Mutations that result solely in microcephaly (primary microcephaly) exist but are less common.<ref name="BMC">{{Cite journal|last1=Faheem|first1=Muhammad|last2=Naseer|first2=Muhammad Imran|last3=Rasool|first3=Mahmood|last4=Chaudhary|first4=Adeel G|last5=Kumosani|first5=Taha A|last6=Ilyas|first6=Asad Muhammad|last7=Pushparaj|first7=Peter Natesan|last8=Ahmed|first8=Farid|last9=Algahtani|first9=Hussain A|last10=Al-Qahtani|first10=Mohammad H|last11=Saleh Jamal|first11=Hasan|date=2015 |title=Molecular genetics of human primary microcephaly: an overview|journal=[[BioMed Central#Journals|BMC Medical Genomics]]|volume=8|issue=Suppl 1|pages=S4|doi=10.1186/1755-8794-8-S1-S4 |pmc=4315316|pmid=25951892 |doi-access=free }}</ref> External toxins to the embryo, such as [[alcohol during pregnancy]] or [[vertically transmitted infections]], can also result in microcephaly.<ref name="NIH2015" /> Microcephaly serves as an important [[neurological]] indication or warning sign, but no uniformity exists in its definition. It is usually defined as a [[Human head#Anthropometry|head circumference]] (HC) more than two [[standard deviation]]s below the mean for age and sex.<ref>{{cite journal |last1=Leviton |first1=A. |last2=Holmes |first2=L.B. |last3=Allred |first3=E.N. |last4=Vargas  |first4=J. |title=Methodologic issues in epidemiologic studies of congenital microcephaly |journal=[[Early Human Development|Early Hum Dev]] |year=2002 |volume=69 |issue=1 |pages=91–105 |doi=10.1016/S0378-3782(02)00065-8 |pmid=12324187 }}</ref><ref>{{cite journal |last1=Opitz |first1=J. M. |last2=Holt |first2=M. C. |title=Microcephaly: general considerations and aids to nosology |journal=Journal of Craniofacial Genetics and Developmental Biology |year=1990 |volume=10 |issue=2 |pages=75–204 |pmid=2211965 }}</ref> Some academics advocate defining it as head circumference more than three standard deviations below the mean for the age and sex.<ref>{{cite book |last1=Behrman |first1=R.E. |last2=Kligman |first2=R. M. |last3=Jensen |first3=H.B. |year=2000 |title=Nelson's Textbook of Pediatrics |edition=16th |location=Philadelphia |publisher=WB Saunders |isbn=978-0-7216-7767-5 |oclc=44552900 |url-access=registration |url=https://archive.org/details/nelsontextbookof00behr }}</ref>

<!-- Treatment and prognosis -->
There is no specific treatment that returns the head size to normal.<ref name=NIH2015/> In general, life expectancy for individuals with microcephaly is reduced, and the [[prognosis]] for normal brain function is poor. Occasional cases develop normal intelligence and grow normally (apart from persistently small head circumference).<ref name=NIH2015/><ref name="Stoler-Poria Lev Schweiger Lerman-Sagie pp. 154–158">{{cite journal |last1=Stoler-Poria |first1=S. |last2=Lev |first2=D. |last3=Schweiger |first3=A. |last4=Lerman-Sagie |first4=T. |last5=Malinger |first5=G. |title=Developmental outcome of isolated fetal microcephaly |journal=[[International Society of Ultrasound in Obstetrics and Gynecology#Journal|Ultrasound in Obstetrics and Gynecology]] |publisher=Wiley |volume=36 |issue=2 |date=2010-01-12 |issn=0960-7692 |doi=10.1002/uog.7556 |pages=154–8 |pmid=20069548 |s2cid=30379486|doi-access=free }}</ref> It is reported that in the United States, microcephaly occurs in 1 in 800-5,000 births.<ref name="CDC">{{Cite web|url=https://www.cdc.gov/ncbddd/birthdefects/microcephaly.html|title=Facts about Microcephaly {{!}} Birth Defects {{!}} National Center on Birth Defects and Developmental Disabilities|date=2016-12-07|website=[[Centers for Disease Control and Prevention]]|access-date=2019-07-30}}</ref>

==Signs and symptoms==
[[File:Peterson 291-292.jpg|thumb|Microcephaly (left) vs. normocephaly (right)]]
[[Image:Microcephaly.png|thumb|Neural scans of a normal-sized skull (left) and a case of microcephaly (right)]]
There are a variety of symptoms that can occur in children. [[Infant]]s with microcephaly are born with either a normal or reduced head size.<ref name="Stanford">{{Cite web|url=https://www.stanfordchildrens.org/en/topic/default?id=microcephaly-90-P02610|title=Microcephaly|website=[[Stanford University Medical Center|Stanford Children's Health]]|access-date=2 August 2019}}</ref> Subsequently, the head fails to grow, while the face continues to develop at a normal rate, producing a child with a small head and a receding forehead, and a loose, often wrinkled [[scalp]].<ref>{{Cite web|url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet|title=Cephalic Disorders Fact Sheet|website=National Institute of Neurological Disorders and Stroke |access-date=2019-08-02 |archiveurl=https://web.archive.org/web/20190727155215/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet |archivedate=2019-07-27|url-status=dead}}</ref> As the child grows older, the smallness of the [[human skull|skull]] becomes more obvious, although the entire body also is often underweight and [[Dwarfism|dwarfed]].<ref name="Stanford" />

Severely impaired [[:wikt:intellectual|intellectual]] development is common, but disturbances in [[motor function]]s may not appear until later in life.<ref name="Stanford" /> Affected newborns generally have striking [[neurological]] defects and [[seizure]]s.<ref name="Stanford" /> Development of motor functions and [[Speech communication|speech]] may be delayed. [[Hyperactive|Hyperactivity]] and intellectual disability are common occurrences, although the degree of each varies. [[Convulsion]]s may also occur. Motor ability varies, ranging from [[:wikt:clumsy|clumsiness]] in some to [[spastic quadriplegia]] in others.<ref>{{Cite web|url=https://www.malacards.org/card/microcephaly_with_spastic_quadriplegia|title=Microcephaly with Spastic Quadriplegia disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials|website=www.malacards.org|access-date=2019-08-02}}</ref>

==Causes==
Microcephaly is a type of [[cephalic disorder]]. It has been classified in two types based on the onset:<ref>{{cite journal |last1=Ashwal |first1=S. |last2=Michelson |first2=D. |last3=Plawner |first3=L. |last4=Dobyns |first4=W. B. |year=2009 |title=Practice Parameter: Evaluation of the child with microcephaly (an evidence-based review) |journal=[[Neurology (journal)|Neurology]] |volume=73 |issue=11 |pages=887–897 |doi=10.1212/WNL.0b013e3181b783f7 |pmid=19752457 |pmc=2744281 }}</ref>

===Congenital===
{{More citations needed section|date=February 2016}}
* Isolated
*# Familial ([[autosomal recessive]]) microcephaly<ref name="Health Encyclopedia">{{Cite encyclopedia|url=https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=90&ContentID=P02610|title=Microcephaly in Children |encyclopedia=Health Encyclopedia |publisher=University of Rochester Medical Center|access-date=2019-07-30}}</ref>
*# [[Autosomal dominant]] microcephaly<ref>{{Cite web|url=https://rarediseases.info.nih.gov/diseases/3605/microcephaly-autosomal-dominant|title=Microcephaly autosomal dominant|publisher=Genetic and Rare Diseases Information Center|access-date=2019-07-30|archive-date=2020-09-21|archive-url=https://web.archive.org/web/20200921191508/https://rarediseases.info.nih.gov/diseases/3605/microcephaly-autosomal-dominant|url-status=dead}}</ref><ref>{{OMIM|617520|Microcephaly 18, Primary, Autosomal Dominant; MCPH18}}</ref>
*# [[X-linked]] microcephaly<ref name="Health Encyclopedia" />
*# Chromosomal (balanced rearrangements and ring chromosome)
* Syndromes
** Chromosomal
**# [[Poland syndrome]]<ref>{{Cite web|url=https://rarediseases.info.nih.gov/diseases/7412/poland-syndrome|title=Poland syndrome |publisher=Genetic and Rare Diseases Information Center |access-date=2019-07-30}}</ref>
**# [[Down syndrome]]<ref>{{Cite web|url=https://www.who.int/news-room/fact-sheets/detail/microcephaly|title=Microcephaly|publisher=World Health Organization|access-date=2019-07-30}}</ref>
**# [[Edward syndrome]]<ref>{{Cite web|title=Trisomy 18: MedlinePlus Medical Encyclopedia|url=https://medlineplus.gov/ency/article/001661.htm|access-date=2020-10-29|website=medlineplus.gov|language=en}}</ref>
**# [[Patau syndrome]]<ref>{{Cite web|title=Trisomy 13 {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|url=https://rarediseases.info.nih.gov/diseases/7341/trisomy-13|access-date=2020-10-29|website=rarediseases.info.nih.gov}}</ref>
**# Unbalanced rearrangements
** Contiguous gene deletion
**# 4p deletion ([[Wolf–Hirschhorn syndrome]])
**# 5p deletion ([[Cri-du-chat]])
**# 7q11.23 deletion ([[Williams syndrome]])
**# 22q11 deletion ([[DiGeorge syndrome]])
* Single gene defects
*# [[Smith–Lemli–Opitz syndrome]]
*# [[Seckel syndrome]]
*# [[Cornelia de Lange syndrome]]
*# [[Dihydropteridine reductase deficiency]] - in up to 25% of patients<ref name="pmid32456656">{{cite journal | vauthors = Opladen T, López-Laso E, Cortès-Saladelafont E, Pearson TS, Sivri HS, Yildiz Y, Assmann B, Kurian MA, Leuzzi V, Heales S, Pope S, Porta F, García-Cazorla A, Honzík T, Pons R, Regal L, Goez H, Artuch R, Hoffmann GF, Horvath G, Thöny B, Scholl-Bürgi S, Burlina A, Verbeek MM, Mastrangelo M, Friedman J, Wassenberg T, Jeltsch K, Kulhánek J, Kuseyri Hübschmann O | title = Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies | journal = Orphanet Journal of Rare Diseases | volume = 15 | issue = 1 | pages = 126 | date = May 2020 | pmid = 32456656 | pmc = 7251883 | doi = 10.1186/s13023-020-01379-8 | url =  | doi-access = free }}</ref>
*# [[5,10-methenyltetrahydrofolate synthetase deficiency]]
*# [[Holoprosencephaly]]
*# [[Primary microcephaly]]<ref>{{cite journal|last1=Szczepanski|first1=Sandra|last2=Hussain|first2=MuhammadSajid|last3=Sur|first3=Ilknur|last4=Altmüller|first4=Janine|last5=Thiele|first5=Holger|last6=Abdullah|first6=Uzma|last7=Waseem|first7=SyedaSeema|last8=Moawia|first8=Abubakar|last9=Nürnberg|first9=Gudrun|last10=Noegel|first10=Angelika Anna|last11=Baig|first11=Shahid Mahmood|last12=Nürnberg|first12=Peter|title=A novel homozygous splicing mutation of CASC5 causes primary microcephaly in a large Pakistani family|journal=Human Genetics|date=30 November 2015|volume=135|issue=2|pages=157–170|doi=10.1007/s00439-015-1619-5|pmid=26621532|s2cid=2295608}}</ref>
*# [[Wiedemann-Steiner syndrome]]
* Acquired
** Disruptive injuries
**# [[Ischemic stroke]]<ref name="UpToDate">{{Cite web|url=https://www.uptodate.com/contents/microcephaly-in-infants-and-children-etiology-and-evaluation|title=Microcephaly in infants and children: Etiology and evaluation|work=[[UpToDate]]|access-date=2019-08-02}}</ref>
**# [[Hemorrhagic stroke]]<ref name="UpToDate" />
**# Death of a monozygotic twin
** [[Vertically transmitted infection]]s
**# [[Congenital cytomegalovirus infection]]<ref name="Mayo Clinic">{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/microcephaly/symptoms-causes/syc-20375051|title=Microcephaly - Symptoms and causes|website=[[Mayo Clinic]]|access-date=2019-07-30}}</ref>
**# [[Toxoplasmosis]]<ref name="Mayo Clinic" />
**# [[Congenital rubella syndrome]]<ref name="Mayo Clinic" />
**# [[Congenital varicella syndrome]]<ref name="Mayo Clinic" />
**# [[Zika virus]] (see [[Zika fever#Microcephaly]])<ref>{{cite journal|title=Interim Guidelines for Pregnant Women During a Zika Virus Outbreak — United States, 2016|date=January 22, 2016|volume=65|issue=2|pages=30–33|journal=Morbidity and Mortality Weekly Report|author1=Emily E. Petersen|author2=Erin Staples|author3=Dana Meaney-Delman|author4=Marc Fischer|author5=Sascha R. Ellington|author6=William M. Callaghan|author7=Denise J. Jamieson|author7-link=Denise J. Jamieson|doi=10.15585/mmwr.mm6502e1|pmid=26796813|doi-access=free}}</ref>
** Drugs
**# [[Fetal hydantoin syndrome]]<ref name="Mayo Clinic" />
**# [[Fetal alcohol syndrome]]<ref name="Mayo Clinic" />
* Other
*# [[Radiation]] exposure to mother
*# Maternal [[malnutrition]]<ref name="Mayo Clinic" />
*# Maternal [[phenylketonuria]]<ref name="Mayo Clinic" />
*# Poorly controlled [[gestational diabetes]]
*# [[Hyperthermia]]
*# [[Maternal hypothyroidism]]
*# [[Placental insufficiency]]
*# [[Craniosynostosis]]<ref name="Mayo Clinic" />

===Postnatal onset===
{{More citations needed section|date=February 2016}}
* Genetic
** Inborn errors of metabolism
**# [[Congenital disorder of glycosylation]]<ref>{{Cite web|url=https://rarediseases.org/rare-diseases/congenital-disorders-of-glycosylation/|title=Congenital Disorders of Glycosylation|website=NORD (National Organization for Rare Disorders)|access-date=2019-08-01}}</ref>
**# [[Mitochondrial disorders]]<ref>{{Cite web|url=https://www.mito.org.au/mito-info/|title=Mito Info|website=Mito Foundation|access-date=2019-08-01}}</ref>
**# [[Peroxisomal disorder]]<ref>{{Cite web|url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=912|title=Zellweger syndrome|website=Orphanet|access-date=2019-08-01}}</ref>
**# [[Glucose transporter]] defect<ref>{{Cite web|url=https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome|title=GLUT1 deficiency syndrome|last=Reference|first=Genetics Home|website=Genetics Home Reference|access-date=2019-08-01}}</ref>
**# [[Menkes disease]]
**# [[Congenital disorders of amino acid metabolism]]<ref>{{Cite web|url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=2209&lng=EN|title=Maternal phenylketonuria|website=Orphanet|access-date=2019-08-01}}</ref>
**# [[Organic acidemia]]<ref>{{Cite journal|last1=Reddy|first1=Nihaal|last2=Calloni|first2=Sonia F.|last3=Vernon|first3=Hilary J.|last4=Boltshauser|first4=Eugen|last5=Huisman|first5=Thierry A. G. M.|last6=Soares|first6=Bruno P.|date=2018-05-01|title=Neuroimaging Findings of Organic Acidemias and Aminoacidopathies|journal=RadioGraphics|volume=38|issue=3|pages=912–931|doi=10.1148/rg.2018170042|pmid=29757724|issn=0271-5333|doi-access=free}}</ref>
* Syndromes
** Contiguous gene deletion
**# 17p13.3 deletion ([[Miller–Dieker syndrome]])<ref>{{OMIM|247200|Miller-Dieker Lissencephaly Syndrome; MDLS}}</ref>
** Single gene defects
**# [[Rett syndrome]] (primarily girls)
**# [[Nijmegen breakage syndrome]]
**# X-linked [[lissencephaly]] with abnormal genitalia
**# [[Aicardi–Goutières syndrome]]
**# [[Ataxia telangiectasia]]
**# [[Cohen syndrome]]
**# [[Cockayne syndrome]]
* Acquired
** Disruptive injuries
**# [[Traumatic brain injury]]<ref>{{Citation|last1=Joyce|first1=Tina|title=Pediatric Abusive Head Trauma (Shaken Baby Syndrome)|date=2019|url=http://www.ncbi.nlm.nih.gov/books/NBK499836/|work=National Center for Biotechnology Information|publisher=AU.S. National Library of Medicine|pmid=29763011|access-date=2019-07-30|last2=Huecker|first2=Martin R.}}</ref>
**# [[Hypoxic-ischemic encephalopathy]]<ref name="Mayo Clinic" />
**# [[Ischemic stroke]]<ref name="UpToDate" />
**# [[Hemorrhagic stroke]]<ref name="UpToDate" />
** Infections
**# Congenital [[HIV encephalopathy]]<ref>{{Cite journal|last1=Donald|first1=Kirsten A.|last2=Walker|first2=Kathleen G.|last3=Kilborn|first3=Tracy|last4=Carrara|first4=Henri|last5=Langerak|first5=Nelleke G|last6=Eley|first6=Brian|last7=Wilmshurst|first7=Jo M|date=2015|title=HIV Encephalopathy: pediatric case series description and insights from the clinic coalface|journal=AIDS Research and Therapy|volume=12|issue=1|page=2|doi=10.1186/s12981-014-0042-7|issn=1742-6405|pmc=4297380|pmid=25598835 |doi-access=free }}</ref>
**# [[Meningitis]]<ref>{{Cite journal|last1=Tibussek|first1=Daniel|last2=Sinclair|first2=Adriane|last3=Yau|first3=Ivanna|last4=Teatero|first4=Sarah|last5=Fittipaldi|first5=Nahuel|last6=Richardson|first6=Susan E.|last7=Mayatepek|first7=Ertan|last8=Jahn|first8=Peter|last9=Askalan|first9=Rand|date=2015|title=Late-Onset Group B Streptococcal Meningitis Has Cerebrovascular Complications|journal=The Journal of Pediatrics|volume=166|issue=5|pages=1187–92.e1|doi=10.1016/j.jpeds.2015.02.014|pmid=25919727}}</ref>
**# [[Encephalitis]]<ref>{{Cite journal|last1=Ramos|first1=Regina|last2=Viana|first2=Rafaela|last3=Brainer-Lima|first3=Alessandra|last4=Florêncio|first4=Telma|last5=Carvalho|first5=Maria Durce|last6=van Der Linden|first6=Vanessa|last7=Amorim|first7=Antonio|last8=Rocha|first8=Maria Ângela|last9=Medeiros|first9=Fabíola|date=2017|title=Perinatal Chikungunya Virus-Associated Encephalitis Leading to Postnatal-Onset Microcephaly and Optic Atrophy|journal=The Pediatric Infectious Disease Journal|volume=37|issue=1|pages=94–95|doi=10.1097/INF.0000000000001690|pmid=28737626|s2cid=31790738|issn=0891-3668}}</ref>
** Toxins
*** [[Chronic kidney failure]]<ref>{{Cite web|url=https://rarediseases.org/rare-diseases/galloway-mowat-syndrome/|title=Galloway-Mowat Syndrome|website=NORD (National Organization for Rare Disorders)|access-date=2019-08-02|archive-date=2021-03-11|archive-url=https://web.archive.org/web/20210311133130/https://rarediseases.org/rare-diseases/galloway-mowat-syndrome/|url-status=dead}}</ref>
** Deprivation
**# [[Hypothyroidism]]<ref>{{Cite journal|last1=Kurian|first1=Manju A|last2=Jungbluth|first2=Heinz|date=July 2014|title=Genetic disorders of thyroid metabolism and brain development|journal=Developmental Medicine and Child Neurology|volume=56|issue=7|pages=627–634|doi=10.1111/dmcn.12445|issn=0012-1622|pmc=4231219|pmid=24665922}}</ref>
**# [[Anemia]]<ref>{{Cite web|url=https://ghr.nlm.nih.gov/condition/fanconi-anemia|title=Fanconi anemia|last=Reference|first=Genetics Home|website=Genetics Home Reference|access-date=2019-08-02}}</ref>
**# [[Congenital heart disease]]<ref>{{Cite journal|last1=Damlich|first1=Jennifer|last2=Qato|first2=Roa|last3=Cruz|first3=Meredith|last4=Colon|first4=Maria|last5=Wilkins|first5=Isabelle|date=2009-07-01|title=Discussion: 'Microcephaly associated with congenital heart defect' by Barbu et al|url=https://www.ajog.org/article/S0002-9378(09)00556-0/abstract|journal=American Journal of Obstetrics & Gynecology|language=en|volume=201|issue=1|pages=e7–e12|doi=10.1016/j.ajog.2009.05.042|pmid=19576365|issn=0002-9378|doi-access=free}}</ref>
**# [[Malnutrition]]<ref>{{Cite web|url=https://www.cdc.gov/ncbddd/birthdefects/microcephaly.html|title=Facts about Microcephaly |date=2016-12-07|publisher=Centers for Disease Control and Prevention|access-date=2019-08-02}}</ref>

Genetic mutations cause most cases of microcephaly.<ref name="NIH2015" /> Relationships have been found between [[autism]], duplications of genes and [[macrocephaly]] on one side. On the other side, a relationship has been found between [[schizophrenia]], deletions of genes and microcephaly.<ref>{{cite journal |author1-link=Bernard Crespi|last1=Crespi |first1=B. |last2=Stead |first2=P. |last3=Elliot |first3=M. |title=Evolution in health and medicine Sackler colloquium: Comparative genomics of autism and schizophrenia |journal=  Proceedings of the National Academy of Sciences of the United States of America|volume=107 |issue=Suppl 1 |pages=1736–41 |date=January 2010 |pmid=19955444 |pmc=2868282 |doi=10.1073/pnas.0906080106 |bibcode=2010PNAS..107.1736C |doi-access=free }}</ref><ref>{{cite journal |title=Rare chromosomal deletions and duplications increase risk of schizophrenia |journal=Nature |volume=455 |issue=7210 |pages=237–241 |date=September 2008 |pmid=18668038 |doi=10.1038/nature07239 |bibcode = 2008Natur.455..237S |last1=Stone |first1=Jennifer L. |last2=O'Donovan |first2=Michael C. |last3=Gurling |first3=Hugh |last4=Kirov |first4=George K. |last5=Blackwood |first5=Douglas H. R. |last6=Corvin |first6=Aiden |last7=Craddock |first7=Nick J. |last8=Gill |first8=Michael |last9=Hultman |first9=Christina M. |last10=Lichtenstein |first10=Paul |last11=McQuillin |first11=Andrew |last12=Pato |first12=Carlos N. |last13=Ruderfer |first13=Douglas M. |last14=Owen |first14=Michael J. |last15=St Clair |first15=David |last16=Sullivan |first16=Patrick F. |last17=Sklar |first17=Pamela |last18=Purcell (Leader) |first18=Shaun M. |last19=Stone |first19=Jennifer L. |last20=Ruderfer |first20=Douglas M. |last21=Korn |first21=Joshua |last22=Kirov |first22=George K. |last23=MacGregor |first23=Stuart |last24=McQuillin |first24=Andrew |last25=Morris |first25=Derek W. |last26=O'Dushlaine |first26=Colm T. |last27=Daly |first27=Mark J. |last28=Visscher |first28=Peter M. |last29=Holmans |first29=Peter A. |last30=o'Donovan |first30=Michael C. |display-authors=6 |pmc=3912847}}</ref><ref>{{cite journal |vauthors=Dumas L, Sikela JM |title=DUF1220 domains, cognitive disease, and human brain evolution |journal=Cold Spring Harb. Symp. Quant. Biol. |volume=74 |pages=375–382 |year=2009 |pmid=19850849 |pmc=2902282 |doi=10.1101/sqb.2009.74.025 }}</ref> Several genes have been designated "MCPH" genes, after [[microcephalin]] (''MCPH1''), based on their role in brain size and primary microcephaly syndromes when mutated. In addition to microcephalin, these include ''[[WDR62]]'' (''MCPH2''), ''[[CDK5RAP2]]'' (''MCPH3''), ''[[KNL1]]'' (''MCPH4''), [[ASPM (gene)|''ASPM'']] (''MCPH5''), ''[[CENPJ]]'' (''MCPH6''), ''[[STIL]]'' (''MCPH7''), ''[[CEP135]]'' (''MCPH8''), ''[[CEP152]]'' (''MCPH9''), ''[[ZNF335]]'' (''MCPH10''), ''[[PHC1]]'' (''MCPH11'') and ''[[CDK6]]'' (''MCPH12'').<ref name="BMC" /> Moreover, an association has been established between common genetic variants within known microcephaly genes (such as ''MCPH1'' and ''CDK5RAP2'') and normal variation in brain structure as measured with [[magnetic resonance imaging]] (MRI){{nsmdns}}i.e., primarily brain [[Cerebral cortex|cortical]] surface area and total brain volume.<ref name="Rimol_2010">{{cite journal |bibcode=2010PNAS..107..384R |jstor=40536283 |title=Sex-dependent association of common variants of microcephaly genes with brain structure |last1=Rimol |first1=Lars M. |last2=Agartz |first2=Ingrid |last3=Djurovic |first3=Srdjan |last4=Brown |first4=Andrew A. |last5=Roddey |first5=J. Cooper |last6=Kahler |first6=Anna K. |last7=Mattingsdal |first7=Morten |last8=Athanasiu |first8=Lavinia |last9=Joyner |first9=Alexander H. |last10=Schork |first10=N. J. |last11=Halgren |first11=E. |last12=Sundet |first12=K. |last13=Melle |first13=I. |last14=Dale |first14=A. M. |last15=Andreassen |first15=O. A. |last16=Weiner |first16=M. |last17=Thal |first17=L. |last18=Petersen |first18=R. |last19=Jack |first19=C. R. |last20=Jagust |first20=W. |last21=Trojanowki |first21=J. |last22=Toga |first22=A. W. |last23=Beckett |first23=L. |last24=Green |first24=R. C. |last25=Gamst |first25=A. |last26=Potter |first26=W. Z. |last27=Montine |first27=T. |last28=Anders |first28=D. |last29=Bernstein |first29=M. |last30=Felmlee |first30=J. |volume=107 |year=2010 |pages=384–8 |journal=Proceedings of the National Academy of Sciences |doi=10.1073/pnas.0908454107 |pmid=20080800 |issue=1 |pmc=2806758|display-authors=6 |doi-access=free }}</ref>

===Arbovirus===
[[Arthropod bites and stings|Bites and stings from Arthropods]] can often be a cause of [[disease vector|vector-borne diseases]]. These include [[mosquitoes]], [[fleas]], [[sand flies]], [[lice]], [[ticks]], and [[mites]] that are [[hematophagous]] vectors. The [[Centers for Disease Control]] (CDC) stated that "mosquitoes kill more people than any other creature and considers that mosquitoes are "the most dangerous animals on earth".<ref>{{cite web |title=Mosquitos kill more people than any other creature, the CDC warns |website=NPR.org  |url=https://www.npr.org/2024/07/08/nx-s1-5026612/mosquitos-kill-more-people-than-any-other-creature-the-cdc-warns |publisher=NPR Morning Edition|date= 8 July 2024|access-date=6 October 2024|archive-url= |archive-date= }}</ref>

The spread of [[Aedes]] mosquito-borne [[Zika virus]] has been implicated in increasing levels of congenital microcephaly by the [[International Society for Infectious Diseases]] and the US [[Centers for Disease Control and Prevention]].<ref>{{cite web |title=Zika virus - Brazil: confirmed Archive Number: 20150519.3370768 |website=Pro-MED-mail |url=http://www.promedmail.org/direct.php?id=3370768 |publisher=International Society for Infectious Diseases |url-status=live |archive-url=https://web.archive.org/web/20160130023132/http://www.promedmail.org/direct.php?id=3370768 |archive-date=2016-01-30 }}</ref> Zika can spread from a pregnant woman to her fetus. This can result in other severe brain malformations and birth defects.<ref name="NEJM201604">{{cite journal|last1=Rasmussen|first1=Sonja A.|last2=Jamieson|first2=Denise J.|last3=Honein|first3=Margaret A.|last4=Petersen|first4=Lyle R.|title=Zika Virus and Birth Defects — Reviewing the Evidence for Causality|journal=New England Journal of Medicine|date=13 April 2016|doi=10.1056/NEJMsr1604338|volume=374|issue=20|pages=1981–7|pmid=27074377|s2cid=20675635|doi-access=free}}</ref><ref>{{cite web|title=CDC Concludes Zika Causes Microcephaly and Other Birth Defects|url=https://www.cdc.gov/media/releases/2016/s0413-zika-microcephaly.html|website=CDC|access-date=1 June 2016|date=13 April 2016|url-status=live|archive-url=https://web.archive.org/web/20160531221123/http://www.cdc.gov/media/releases/2016/s0413-zika-microcephaly.html|archive-date=31 May 2016}}</ref><ref>{{cite web| url=https://www.cdc.gov/media/releases/2016/s0315-zika-virus-travel.html| title=CDC issues interim travel guidance related to Zika virus for 14 Countries and Territories in Central and South America and the Caribbean| publisher=Centers for Disease Control and Prevention| date=2016-01-15| access-date=2016-01-17| url-status=live| archive-url=https://web.archive.org/web/20160118024439/http://www.cdc.gov/media/releases/2016/s0315-zika-virus-travel.html| archive-date=2016-01-18}}</ref><ref>{{cite web|url=http://arstechnica.co.uk/science/2016/01/cdc-issues-travel-advisory-for-14-countries-with-alarming-viral-outbreaks/|title=CDC issues travel advisory for 14 countries with alarming viral outbreaks|author=Beth Mole|publisher=[[Condé Nast]]|work=[[Ars Technica]]|date=2016-01-17|access-date=2016-01-17|url-status=live|archive-url=http://archive.wikiwix.com/cache/20160118092344/http://arstechnica.co.uk/science/2016/01/cdc-issues-travel-advisory-for-14-countries-with-alarming-viral-outbreaks/|archive-date=2016-01-18}}</ref> A study published in The New England Journal of Medicine has documented a case in which they found evidence of the Zika virus in the brain of a fetus that displayed the morphology of microcephaly.<ref>{{Cite journal|last1=Mlakar|first1=Jernej|last2=Korva|first2=Misa|last3=Tul|first3=Nataša|last4=Popović|first4=Mara|last5=Poljšak-Prijatelj|first5=Mateja|last6=Mraz|first6=Jerica|last7=Kolenc|first7=Marko|last8=Resman Rus|first8=Katarina|last9=Vesnaver Vipotnik|first9=Tina|date=2016-03-10|title=Zika Virus Associated with Microcephaly|journal=New England Journal of Medicine|volume=374|issue=10|pages=951–8|doi=10.1056/NEJMoa1600651|issn=0028-4793|pmid=26862926|s2cid=205099844|doi-access=free}}</ref>

===Microlissencephaly===
{{Main|Microlissencephaly}}
[[Microlissencephaly]] is microcephaly combined with [[lissencephaly]] (smooth brain surface due to absent [[Sulcus (neuroanatomy)|sulci]] and [[gyri]]). Most cases of microlissencephaly are described in consanguineous families, suggesting an [[autosomal recessive inheritance]].<ref name="Cavallin">{{Cite journal|last1=Cavallin|first1=Mara|last2=Rujano|first2=Maria A.|last3=Bednarek|first3=Nathalie|last4=Medina-Cano|first4=Daniel|last5=Bernabe Gelot|first5=Antoinette|last6=Drunat|first6=Severine|last7=Maillard|first7=Camille|last8=Garfa-Traore|first8=Meriem|last9=Bole|first9=Christine|date=2017-10-01|title=WDR81 mutations cause extreme microcephaly and impair mitotic progression in human fibroblasts and Drosophila neural stem cells|journal=Brain|volume=140|issue=10|pages=2597–2609|doi=10.1093/brain/awx218|issn=1460-2156|pmid=28969387|doi-access=free}}</ref><ref>{{Cite book|url={{GBUrl|AmZgmGG4Dz0C|pg=PA309}}|title=Caffey's Pediatric Diagnostic Imaging E-Book|last=Coley|first=Brian D.|date=2013 |publisher=Elsevier Health Sciences|isbn=978-1-4557-5360-4 |edition=12th |oclc=847214216}}</ref><ref>{{Cite book|url={{GBUrl|AnVYBAAAQBAJ|pg=PA838}}|title=Fanaroff and Martin's Neonatal-Perinatal Medicine E-Book: Diseases of the Fetus and Infant|last1=Martin|first1=Richard J.|last2=Fanaroff|first2=Avroy A.|last3=Walsh|first3=Michele C.|date=2014 |publisher=Elsevier Health Sciences|isbn=978-0-323-29537-6 |oclc=909892605}}</ref>

===Historical causes of microcephaly===

After the dropping of [[atomic bombs]] "Little Boy" on [[Hiroshima]] and "Fat Man" on [[Nagasaki]], several women close to [[ground zero]] who had been pregnant at the time gave birth to children with microcephaly.<ref>{{cite web|url=http://www.pcf.city.hiroshima.jp/kids/KPSH_E/hiroshima_e/sadako_e/subcontents_e/13kousyougai_1_e.html#|title=Aftereffects|archive-url=https://web.archive.org/web/20090525013355/http://www.pcf.city.hiroshima.jp/kids/KPSH_E/hiroshima_e/sadako_e/subcontents_e/13kousyougai_1_e.html|archive-date=2009-05-25|url-status=live}}</ref> Microcephaly was present in 7 children from a group of 11 pregnant women at 11–17 weeks of [[gestation]] who survived the blast at less than {{convert|1.2|km|mi|abbr=on}} from ground zero.<ref name=Kalter10>{{cite book |chapter=Pioneering Studies §Atomic Radiation §Microcephaly and Mental Retardation |chapter-url={{GBUrl|DykKlVU0V-oC|pg=PA21}}|title=Teratology in the Twentieth Century Plus Ten|last1=Kalter|first1=Harold|date=2010 |publisher=Springer |isbn=978-90-481-8820-8 |page=21 |doi=10.1007/978-90-481-8820-8_2}}</ref> Due to their proximity to the bomb, the pregnant women's ''[[Uterus|in utero]]'' children received a [[Relative biological effectiveness|biologically significant radiation dose]] that was relatively high due to the massive [[neutron]] output of the lower explosive-yielding [[Little Boy]].<ref name=Kalter10/> Researchers studied 286 additional children who were in utero during the atomic bombings, and after a year they found these children had a higher incidence of microcephaly and mental retardation.<ref>{{Cite journal|last1=Burrow|first1=Gerard N.|last2=Hamilton|first2=Howard B.|last3=Hrubec|first3=Zdenek|date=June 1964|title=Study of Adolescents Exposed in Utero to the Atomic Bomb, Nagasaki, Japan|journal=[[Yale Journal of Biology and Medicine]]|volume=36|issue=6|pages=430–444 |pmc=2604646|pmid=14173443}}</ref><ref name=Kalter10/>

=== Other relations ===
Intracranial volume also affects this pathology, as it is related with the size of the brain.<ref>{{Cite journal|last1=Adams|first1=Hieab H. H.|last2=Hibar|first2=Derrek P.|last3=Chouraki|first3=Vincent|last4=Stein|first4=Jason L.|last5=Nyquist|first5=Paul A.|last6=Rentería|first6=Miguel E.|last7=Trompet|first7=Stella|last8=Arias-Vasquez|first8=Alejandro|last9=Seshadri|first9=Sudha|year=2016|title=Novel genetic loci underlying human intracranial volume identified through genome-wide association|journal=Nature Neuroscience|volume=19|issue=12|pages=1569–82|doi=10.1038/nn.4398|pmid=27694991|pmc=5227112}}</ref>

==Pathophysiology==

Microcephaly generally is due to the diminished size of the largest part of the human brain, the [[cerebral cortex]], and the condition can arise during embryonic and fetal development due to insufficient [[neural stem cell]] proliferation, impaired or premature [[neurogenesis]], the death of neural [[stem cells]] or [[neurons]], or a combination of these factors.<ref>{{cite journal|last1=Jamuar|first1=SS|last2=Walsh|first2=CA|title=Genomic variants and variations in malformations of cortical development.|journal=Pediatric Clinics of North America|date=June 2015|volume=62|issue=3|pages=571–85|pmid=26022163|doi=10.1016/j.pcl.2015.03.002|pmc=4449454}}</ref> Research in animal models such as rodents has found many genes that are required for normal brain growth. For example, the [[Notch pathway]] genes regulate the balance between stem cell proliferation and [[neurogenesis]] in the stem cell layer known as the [[ventricular zone]], and experimental mutations of many genes can cause microcephaly in mice,<ref>{{cite journal|last1=Rash|first1=BG|last2=Lim|first2=HD|last3=Breunig|first3=JJ|last4=Vaccarino|first4=FM|title=FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis.|journal=The Journal of Neuroscience|date=26 October 2011|volume=31|issue=43|pages=15604–17|pmid=22031906|doi=10.1523/jneurosci.4439-11.2011|pmc=3235689}}</ref> similar to human microcephaly.<ref>{{cite journal|last1=Shen|first1=J|last2=Gilmore|first2=EC|last3=Marshall|first3=CA|last4=Haddadin|first4=M|last5=Reynolds|first5=JJ|last6=Eyaid|first6=W|last7=Bodell|first7=A|last8=Barry|first8=B|last9=Gleason|first9=D|last10=Allen|first10=K|last11=Ganesh|first11=VS|last12=Chang|first12=BS|last13=Grix|first13=A|last14=Hill|first14=RS|last15=Topcu|first15=M|last16=Caldecott|first16=KW|last17=Barkovich|first17=AJ|last18=Walsh|first18=CA|title=Mutations in PNKP cause microcephaly, seizures and defects in DNA repair.|journal=Nature Genetics|date=March 2010|volume=42|issue=3|pages=245–9|pmid=20118933|doi=10.1038/ng.526|pmc=2835984}}</ref><ref>{{cite journal|last1=Alkuraya|first1=FS|last2=Cai|first2=X|last3=Emery|first3=C|last4=Mochida|first4=GH|last5=Al-Dosari|first5=MS|last6=Felie|first6=JM|last7=Hill|first7=RS|last8=Barry|first8=BJ|last9=Partlow|first9=JN|last10=Gascon|first10=GG|last11=Kentab|first11=A|last12=Jan|first12=M|last13=Shaheen|first13=R|last14=Feng|first14=Y|last15=Walsh|first15=CA|title=Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected].|journal=American Journal of Human Genetics|date=13 May 2011|volume=88|issue=5|pages=536–47|pmid=21529751|doi=10.1016/j.ajhg.2011.04.003|pmc=3146728}}</ref> Mutations of the [[ASPM (gene)|abnormal spindle-like microcephaly-associated (ASPM) gene]] are associated with microcephaly in humans and a knockout model has been developed in [[ferret]]s that exhibits severe microcephaly.<ref name="JohnsonSun2018">{{cite journal|last1=Johnson|first1=Matthew B.|last2=Sun|first2=Xingshen|last3=Kodani|first3=Andrew|last4=Borges-Monroy|first4=Rebeca|last5=Girskis|first5=Kelly M.|last6=Ryu|first6=Steven C.|last7=Wang|first7=Peter P.|last8=Patel|first8=Komal|last9=Gonzalez|first9=Dilenny M.|last10=Woo|first10=Yu Mi|last11=Yan|first11=Ziying|last12=Liang|first12=Bo|last13=Smith|first13=Richard S.|last14=Chatterjee|first14=Manavi|last15=Coman|first15=Daniel|last16=Papademetris|first16=Xenophon|last17=Staib|first17=Lawrence H.|last18=Hyder|first18=Fahmeed|last19=Mandeville|first19=Joseph B.|last20=Grant|first20=P. Ellen|last21=Im|first21=Kiho|last22=Kwak|first22=Hojoong|last23=Engelhardt|first23=John F.|last24=Walsh|first24=Christopher A.|last25=Bae|first25=Byoung-Il|title=Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size|journal=Nature|volume=556|issue=7701|year=2018|pages=370–5|doi=10.1038/s41586-018-0035-0|pmid=29643508|pmc=6095461|bibcode=2018Natur.556..370J}}</ref> In addition, viruses such as [[cytomegalovirus]] (CMV) or [[Zika]] have been shown to infect and kill the primary stem cell of the brain—the [[radial glial cell]], resulting in the loss of future daughter neurons.<ref>{{cite journal|last1=Nowakowski|first1=TJ|last2=Pollen|first2=AA|last3=Di Lullo|first3=E|last4=Sandoval-Espinosa|first4=C|last5=Bershteyn|first5=M|last6=Kriegstein|first6=AR|title=Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.|journal=Cell Stem Cell|date=5 May 2016|volume=18|issue=5|pages=591–6|pmid=27038591|pmc=4860115|doi=10.1016/j.stem.2016.03.012}}</ref><ref>{{cite journal|last1=Li|first1=C|last2=Xu|first2=D|last3=Ye|first3=Q|last4=Hong|first4=S|last5=Jiang|first5=Y|last6=Liu|first6=X|last7=Zhang|first7=N|last8=Shi|first8=L|last9=Qin|first9=CF|last10=Xu|first10=Z|title=Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice.|journal=Cell Stem Cell|date=7 July 2016|volume=19|issue=1|pages=120–6|pmid=27179424|doi=10.1016/j.stem.2016.04.017|doi-access=free}}</ref> The severity of the condition may depend on the timing of infection during pregnancy.{{citation needed|date=January 2021}}

Microcephaly is a feature common to several different genetic disorders arising from a deficiency in the cellular [[DNA damage (naturally occurring)|DNA damage]] response.<ref>{{cite journal |vauthors=O'Driscoll M, Jeggo PA |title=The role of the DNA damage response pathways in brain development and microcephaly: insight from human disorders |journal=DNA Repair (Amst) |volume=7 |issue=7 |pages=1039–50 |date=July 2008 |pmid=18458003 |doi=10.1016/j.dnarep.2008.03.018 }}</ref> Individuals with the following DNA damage response disorders exhibit microcephaly: [[Nijmegen breakage syndrome]], ATR-[[Seckel syndrome]], [[MCPH1]]-dependent primary microcephaly disorder, [[XPA|xeroderma pigmentosum complementation group A]] deficiency, [[Fanconi anemia]], [[LIG4 syndrome|ligase 4 deficiency syndrome]] and [[Bloom syndrome]]. These findings suggest that a normal DNA damage response is critical during [[development of the nervous system|brain development]], perhaps to protect against induction of [[apoptosis]] by DNA damage occurring in [[neuron]]s.<ref>{{cite journal |vauthors=Ribeiro JH, Altinisik N, Rajan N, Verslegers M, Baatout S, Gopalakrishnan J, Quintens R |title=DNA damage and repair: underlying mechanisms leading to microcephaly |journal=Front Cell Dev Biol |volume=11 |issue= |pages=1268565 |date=2023 |pmid=37881689 |pmc=10597653 |doi=10.3389/fcell.2023.1268565 |doi-access=free }}</ref>

==Treatment==
[[File:Bebê com microcefalia 01.jpg|thumb|Baby with microcephaly during a [[physical therapy]] session]]
There is no known cure for microcephaly.<ref name=NIH2015/> Treatment is [[symptom]]atic and supportive.<ref name=NIH2015/> Because some cases of microcephaly and its associated symptoms may be a result of amino acid deficiencies, treatment with amino acids in these cases has been shown to improve symptoms such as seizures and motor function delays.<ref>{{Cite journal|last=de Koning|first=T. J.|date=2006|title=Treatment with amino acids in serine deficiency disorders|journal=Journal of Inherited Metabolic Disease|volume=29|issue=2–3|pages=347–351|doi=10.1007/s10545-006-0269-0|pmid=16763900|s2cid=35908740|issn=0141-8955}}</ref>

==History==
People with small heads were displayed as a public spectacle in [[ancient Rome]].<ref>{{cite book|last=Stories|first=Wander|date=4 February 2015|title=Colosseum in Rome: a travel guide and tour as with the best local guide|publisher=WanderStories |url={{GBUrl|XR99BgAAQBAJ|pg=PT53}}|isbn=978-9-949-51606-3}}</ref>

People with microcephaly were sometimes sold to [[freak shows]] in North America and Europe in the 19th and early 20th centuries, where they were known by the name "pinheads". Many of them were presented as different species (e.g., "monkey man") and described as being the [[Transitional fossil|missing link]].<ref>{{cite journal|last1=Mateen|first1=F.J.|last2=Boes|first2=C.J.|year=2010|title='Pinheads': the exhibition of neurologic disorders at 'The Greatest Show on Earth'|journal=Neurology|volume=75|issue=22|pages=2028–32|pmid=21115959|doi=10.1212/WNL.0b013e3181ff9636|s2cid=207118420}}</ref> Famous examples include [[Zip the Pinhead]] (although he may not have had microcephaly), [[Maximo and Bartola]] and [[Schlitzie|Schlitzie the Pinhead]].<ref>{{cite web|url=http://www.thehumanmarvels.com/zip-the-pinhead-what-is-it/|date=16 October 2010|title=Zip the Pinhead: What is it?|work=The Human Marvels|url-status=live|archive-url=https://web.archive.org/web/20160414081840/http://www.thehumanmarvels.com/zip-the-pinhead-what-is-it/|archive-date=14 April 2016}}</ref> Stars of the 1932 film [[Freaks (1932 film)|Freaks]] were cited as influences on the development of the long-running [[comic strip]] character [[Zippy the Pinhead]], created by [[Bill Griffith]].<ref>{{cite web|year=1995|url=http://www.zippythepinhead.com/pages/aaishehavingfunyet.html|title=Interview with Bill Griffith|website=ZippythePinhead.com|publisher=Goblin Magazine|access-date=13 February 2013|url-status=live|archive-url=https://web.archive.org/web/20120131175615/http://www.zippythepinhead.com/pages/aaishehavingfunyet.html|archive-date=31 January 2012}}</ref>
<gallery>
File:Triboulet.png|[[Triboulet (playwright)|Triboulet]], a French court [[jester]], 1461
File:Die Gartenlaube (1868) b 204.jpg|18-year-old Emil R., 1868
File:Idiotie - Microcéphalie.jpg|Elderly female, 1888/89
File:Microcephalic high-grade idiot.jpg|52-year-old female, 1900
File:Microcephalus A.jpg|10-year-old male, 1904
File:Microcephalic idiot.jpg|20-year-old female, 1906/07
File:Microcephalic idiots.jpg|3 relatives, 1913
File:Microcephaly sister and brother.jpg|18-year-old sister and 9-year-old brother, 1917
File:Various types 1 (detail A, microcephaly).jpg|55-year-old female, 1920 (linear descendant of [[Pocahontas]])
File:Microcephalics (2nd image, EFGHIJ).jpg|6 siblings, 1920
</gallery>

==Notable cases==
* A 'dwarf' of Punt (ancient Somalia) was given by the Chief clans as partial tribute to the last ruler of Ancient Egypt's Old Kingdom, [[Pepi II Neferkare]] (6th Dynasty, circa 2125–2080 BC); it could be inferred that this person was also microcephalic. In a letter preserved at the British Museum, the young king gives instructions by letter, "[[Harkhuf]]! The men in your service [escorts; soldiers; sailors; guards, etc.] ought pay sincere care with the dwarf's head while sleeping during the voyage to the palace" (so that it does not fall off). At the same time, it could be for other reasons unrelated to microcephaly, etc.<ref>{{cite journal|last=Kozma|first=Chahira|date=10 October 2005|title=Historical Review - Dwarfs in Ancient Egypt|url=http://www.academia.dk/MedHist/Biografier/PDF/DwarfsInAncientEgypt.pdf|journal=[[American Journal of Medical Genetics]]|volume=140 |issue=4 |pages=303–311 |doi=10.1002/ajmg.a.31068|pmid=16380966 |s2cid=797288 |access-date=17 February 2018|url-status=live|archive-url=https://web.archive.org/web/20170517031228/http://www.academia.dk/MedHist/Biografier/PDF/DwarfsInAncientEgypt.pdf|archive-date=17 May 2017}}</ref>
* ''[[Triboulet (playwright)|Triboulet]]'', a [[jester]] of duke [[René of Anjou]] (not to be confused with the slightly later [[Triboulet]] at the French court).
* Jenny Lee Snow and Elvira Snow, whose stage names were Pip and Flip, respectively, were sisters with microcephaly who acted in the 1932 film ''[[Freaks (1932 film)|Freaks]]''.
* [[Schlitzie|Schlitze "Schlitzie" Surtees]], possibly born Simon Metz, was a widely known sideshow performer and actor, who also appeared in ''[[Freaks (1932 film)|Freaks]]''.
* [[Beetlejuice (entertainer)|Lester "Beetlejuice" Green]], a member of radio host Howard Stern's Wack Pack.

==See also==

{{Portal|Medicine}}
* [[Anencephaly]] (Usually rapidly fatal)
* [[Cerebral rubicon]]
* [[Hydrocephalus|Hydrocephaly]]
* [[Macrocephaly]]
* [[Seckel syndrome]]
* [[Achalasia microcephaly]]
* [[Oropouche orthobunyavirus]]

==References==
{{Reflist}}

== External links ==
{{Medical resources
| ICD11           = {{ICD11|LA05.0}}
|   ICD10          = {{ICD10|Q|02||q|00}}
|   ICD9           = {{ICD9|742.1}}
|   ICDO           =
|   OMIM           = 251200
|   OMIM_mult      =
|   MedlinePlus    = 003272
|   eMedicineSubj  =
|   eMedicineTopic =
|   DiseasesDB     = 22629
|   MeshID         = D008831
|   Scholia        = Q431643
}}

{{wikimedia|collapsible=true|c=Category:Microcephaly|d=Q431643}}
* {{NINDS|Microcephaly}}
* [https://web.archive.org/web/20190727155215/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet NINDS Overview]

{{Congenital malformations and deformations of nervous system}}
{{Authority control}}

[[Category:Congenital disorders of nervous system]]
[[Category:Disorders causing seizures]]