Editing Macrocephaly

{{Short description|Abnormally large head size}}
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'''Macrocephaly''' is a condition in which [[circumference]] of the [[human head]] is abnormally large.<ref>{{cite book |vauthors=Toi A, Malinger G |title=Obstetric Imaging: Fetal Diagnosis and Care |date=2018 |location=Philadelphia, PA |isbn=978-0-323-44548-1 |edition=2nd |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/macrocephaly |archive-url=https://web.archive.org/web/20210324204952/https://www.sciencedirect.com/topics/medicine-and-dentistry/macrocephaly |archive-date=24 March 2021 |chapter=36 - Cortical Development and Disorders}}</ref> It may be pathological or harmless, and can be a [[Heredity|familial genetic]] characteristic. People diagnosed with macrocephaly will receive further [[medical test]]s to determine whether the [[syndrome]] is accompanied by particular [[Disorder (medicine)|disorders]]. Those with [[benign]] or familial macrocephaly are considered to have [[megalencephaly]].

==Causes==
[[File:Macrocephalic idiot.jpg|thumb|Normocephaly (left) vs. macrocephaly (right))]]
Many people with abnormally large heads or large skulls are healthy, but macrocephaly may be pathological. Pathologic macrocephaly may be due to [[megalencephaly]] (enlarged brain), [[hydrocephalus]] (abnormally increased [[cerebrospinal fluid]]), cranial [[hyperostosis]] (bone overgrowth), and other conditions. Pathologic macrocephaly is called "syndromic", when it is associated with any other noteworthy condition, and "nonsyndromic" otherwise. Pathologic macrocephaly may be caused by [[congenital]] anatomic abnormalities, genetic conditions, or by environmental events.<ref name=Williams/>

Many genetic conditions are associated with macrocephaly, including familial macrocephaly related to the holgate gene, [[autism]], [[PTEN (gene)|''PTEN'']] mutations such as [[Cowden disease]], [[neurofibromatosis]] type 1, and [[tuberous sclerosis]]; overgrowth syndromes such as [[Sotos syndrome]] (cerebral gigantism), [[Weaver syndrome]], [[Simpson–Golabi–Behmel syndrome]] (bulldog syndrome), and [[macrocephaly-capillary malformation]] (M-CMTC) syndrome; neurocardiofacial-cutaneous syndromes such as [[Noonan syndrome]], [[Costello syndrome]], [[Gorlin syndrome]],<ref>{{Cite web |url=http://www.gorlinsyndrome.org/EduDocs/General/Nevoid%20Basal%20Cell%20Carcinoma%20Syndrome.pdf |title=Archived copy |access-date=2015-05-04 |archive-url=https://web.archive.org/web/20151009061914/http://www.gorlinsyndrome.org/EduDocs/General/Nevoid%20Basal%20Cell%20Carcinoma%20Syndrome.pdf |archive-date=2015-10-09 |url-status=dead }}</ref> (also known as basal cell nevus syndrome) and [[cardiofaciocutaneous syndrome]]; [[Fragile X syndrome]]; [[leukodystrophies]] (brain [[white matter]] degeneration) such as [[Alexander disease]], [[Canavan disease]], and [[megalencephalic leukoencephalopathy with subcortical cysts]]; and [[glutaric aciduria type 1]] and [[D-2-hydroxyglutaric aciduria]].<ref name=Williams/>

At one end of the genetic spectrum, duplications of chromosomes have been found to be related to autism and macrocephaly; at the other end, deletions of chromosomes have been found to be related to [[schizophrenia]] and [[microcephaly]].<ref>{{cite journal|author=Crespi|display-authors=etal|year=2010|title=Comparative genomics of autism and schizophrenia|journal=PNAS|volume=107|issue=Suppl 1 |pages=1736–1741|doi=10.1073/pnas.0906080106|pmc=2868282|pmid=19955444|doi-access=free}}</ref><ref>{{cite journal | title = Rare chromosomal deletions and duplications increase risk of schizophrenia; The International Schizophrenia Consortium; | journal = Nature | volume = 455| issue = 7210| pages = 237–241 | doi = 10.1038/nature07239 | pmid=18668038 | date=September 2008 | pmc=3912847| author1 = International Schizophrenia Consortium }}</ref><ref>{{cite journal | author = Dumas L. | author2 = Sikela J.M. | year = 2009 | title = DUF1220 Domains, Cognitive Disease, and Human Brain Evolution | journal = Cold Spring Harb. Symp. Quant. Biol.| volume =  74| pages =  375–82| doi = 10.1101/sqb.2009.74.025 | pmid=19850849 | pmc=2902282}}</ref>

Environmental events associated with macrocephaly include infection, neonatal [[intraventricular hemorrhage]] (bleeding within the infant brain), [[subdural hematoma]] (bleeding beneath the outer lining of the brain), [[subdural effusion]] (collection of fluid beneath the outer lining of the brain), and [[arachnoid cyst]]s (cysts on the brain surface).<ref name=Williams/>

In research, cranial height or brain imaging may be used to determine intracranial volume more accurately.<ref name=Williams>{{cite journal |journal= Am J Med Genet A |date=2008 |volume=146A |issue=16 |pages=2023–37 |title= Genetic disorders associated with macrocephaly |vauthors= Williams CA, Dagli A, Battaglia A |doi=10.1002/ajmg.a.32434 |pmid=18629877|s2cid=205309800 |doi-access=free }}</ref>

Below is a list of conditions featuring macrocephaly from [[NCBI]]'s MedGen:<ref>{{Cite web |title=Macrocephaly (Concept Id: C2243051) - MedGen - NCBI |url=https://www.ncbi.nlm.nih.gov/medgen/745757 |access-date=2023-06-30 |website=www.ncbi.nlm.nih.gov |language=en}}</ref>

* [[Achondroplasia]]
* [[Acrocallosal syndrome]]
* [[Adams-Oliver syndrome]] 
* [[Adenosine kinase]] deficiency
* [[Antley-Bixler syndrome]]
* Autosomal dominant [[Kenny-Caffey syndrome]]
* [[Malignant infantile osteopetrosis|Autosomal recessive osteopetrosis]]
* [[Axenfeld-Rieger anomaly]]
* [[B4GALT1]]-[[congenital disorder of glycosylation]]
* [[Bardet-Biedl syndrome]] 
* [[Brittle cornea syndrome]] 
* [[Camptomelic dysplasia]]
* [[Cardio-facio-cutaneous syndrome]]
* [[Cobblestone lissencephaly]] without muscular or ocular involvement
* [[Coffin-Siris syndrome]]
* [[Cohen-Gibson syndrome]]
* [[Cole-Carpenter syndrome]] 
* [[Congenital disorder of glycosylation]], type Iw, autosomal dominant
* [[Agenesis of corpus callosum|Corpus callosum, agenesis of]]
* [[Costello syndrome]]
* [[Cowden syndrome]] 
* [[Craniodiaphyseal dysplasia]], autosomal dominant
* [[Cranioectodermal dysplasia]] 
* [[Craniometaphyseal dysplasia]]
* [[Craniosynostosis]]
* [[D-2-hydroxyglutaric aciduria]]
* Deficiency of [[alpha-mannosidase]]
* [[Desmosterolosis]]
* [[Donnai-Barrow syndrome]]
* [[Early-onset parkinsonism-intellectual disability syndrome]]
* [[Ehlers-Danlos syndrome]], spondylodysplastic type
* [[Epidermolysis bullosa simplex]]
* [[Fragile X syndrome]]
* [[Giant axonal neuropathy]]
* [[Glutaric aciduria]], type 1
* [[Gorlin syndrome]]
* [[Greenberg dysplasia]]
* [[Greig cephalopolysyndactyly syndrome]]
* [[Hamartoma]] of [[hypothalamus]]
* [[Holoprosencephaly]]
* [[Hurler syndrome]]
[[File:Peterson 283.jpg|thumb|Macrocephaly from hydrocephalus]]
* [[Hydrocephalus]], nonsyndromic, autosomal recessive
* [[Hypochondroplasia]]
* [[Hypophosphatemic rickets]] and [[hyperparathyroidism]]
* [[Hypothyroidism]], congenital, nongoitrous
* Ito [[hypomelanosis]]
* [[Joubert syndrome]]
* [[Keipert syndrome]]
* [[Legius syndrome]]
* [[LEOPARD syndrome]] 
* [[Lethal congenital contracture syndrome]] 
* [[MASA syndrome]]
[[File:Stoddart 79.jpg|thumb|Macrocephaly from megalencephaly]]
* [[Megalencephaly]], autosomal dominant
* [[Megalocornea-intellectual disability syndrome]]
* [[MGAT2]]-[[congenital disorder of glycosylation]]
* [[MOMO syndrome]]
* [[Mucopolysaccharidosis type 6]]
* [[Sly syndrome|Mucopolysaccharidosis type 7]]
* [[Mucopolysaccharidosis II|Mucopolysaccharidosis, MPS-II]]
* [[Mucopolysaccharidosis III|Mucopolysaccharidosis, MPS-III-D]]
* [[Muenke syndrome]]
* [[Multiple acyl-CoA dehydrogenase deficiency]]
* [[Multiple congenital anomalies-hypotonia-seizures syndrome]]
* [[Multiple epiphyseal dysplasia]], Al-Gazali type
* [[Myhre syndrome]]
* [[Neurofibromatosis type 1|Neurofibromatosis, type 1]]
* [[Neurofibromatosis-Noonan syndrome]]
* [[Niemann-Pick disease]], type A
* [[Noonan syndrome]]
* [[Opsismodysplasia]]
* [[Optic atrophy]]
* [[Osteopathia striata]] with cranial [[Sclerosis (medicine)|sclerosis]]
* [[Pallister-Killian syndrome]]
* [[Parietal foramina]] 
* Parietal foramina with [[cleidocranial dysplasia]]
* [[Pelger-Huët anomaly]]
* [[Zellweger syndrome|Peroxisome biogenesis disorder 1A (Zellweger)]]
* [[Peroxisome biogenesis disorder]] 4B
* [[Phelan-McDermid syndrome]]
* [[Plasminogen]] deficiency, type I
* [[Primrose syndrome]]
* [[Proteus syndrome]]
* [[Ritscher-Schinzel syndrome]] 
* [[Robinow syndrome]]
* [[Sandhoff disease]]
* [[Schneckenbecken dysplasia]]
* [[Sclerosteosis]] 
* Severe [[X-linked myotubular myopathy]]
* [[Sialuria]]
* [[Simpson-Golabi-Behmel syndrome]] 
* [[Snijders Blok-Campeau syndrome]]
* [[Sotos syndrome]] 
* [[Sturge-Weber syndrome]]
* [[Sulfite oxidase deficiency]] due to [[molybdenum cofactor deficiency]]
* [[Symphalangism]] with multiple anomalies of hands and feet
* Syndromic [[X-linked intellectual disability]]
* [[Thanatophoric dysplasia]] type 1
* [[Vanishing white matter disease]]
* [[Weaver syndrome]]
* X-linked dominant [[chondrodysplasia]], Chassaing-Lacombe type
* X-linked hydrocephalus syndrome
* [[X-linked intellectual disability]] with [[marfanoid habitus]]
* [[Zimmermann-Laband syndrome]] 
* [[ZTTK syndrome]]

==Diagnosis==
Macrocephaly is customarily diagnosed if head circumference is greater than two [[standard deviation]]s (SDs) above the mean.<ref>{{cite book|last1=Fenichel|first1=Gerald M.|title=Clinical Pediatric Neurology: A Signs and Symptoms Approach|url=https://archive.org/details/clinicalpediatri00mdge|url-access=limited|date=2009|publisher=Saunders/Elsevier|location=Philadelphia, PA|isbn=978-1416061854|page=[https://archive.org/details/clinicalpediatri00mdge/page/n410 369]|edition=6th}}</ref> Relative macrocephaly occurs if the measure is less than two SDs above the mean, but is disproportionately above that when ethnicity and stature are considered. Diagnosis can be determined [[Uterus|in utero]] or can be determined within 18–24 months after birth in some cases where head circumference tends to stabilize in [[infant]]s.<ref name=":0">{{Cite web|title=Macrocephaly {{!}} Nicklaus Children's Hospital|url=https://www.nicklauschildrens.org/conditions/macrocephaly|website=www.nicklauschildrens.org|access-date=2020-04-11}}</ref> Diagnosis in infants includes measuring the circumference of the child's head and comparing how significant it falls above the 97.5 percentile of children similar to their demographic. If falling above the 97.5th percentile then the patient will be checked to determine whether there is any [[intracranial pressure]] present and whether or not immediate surgery is needed.<ref name=":02" />  If immediate surgery is not needed then further testing will be done to determine whether the patient has either macrocephaly or benign macrocephaly.

Diagnosis for macrocephaly involves the comparison of the infant's head circumference to that of other infants of the same age and [[ethnicity]]. If a patient is suspected of having macrocephaly molecular testing will be used to confirm diagnosis. Symptoms vary on the cause of macrocephaly on the child and if the child has any other accompanying syndromes which will be determined through molecular testing.

=== Benign or familial macrocephaly ===
Benign macrocephaly can occur without reason or be inherited by one or both parents (in which it is considered benign familial macrocephaly and is considered a [[megalencephaly]] form of macrocephaly). Diagnosis for familial macrocephaly is determined by measuring the head circumference of both parents and comparing it to the child's. Benign and familial macrocephaly is not associated with [[neurological disorder]]s.<ref name=":02">{{Cite book|title=Signs and Symptoms of Genetic Conditions: A Handbook|others=Hudgins, Louanne,, Toriello, Helga V.,, Enns, Gregory M.,, Hoyme, H. Eugene|date = 30 May 2014|isbn=978-0-19-938869-1|location=Oxford|oclc=879421703}}</ref> While benign and familial macrocephaly do not result in neurological disorders, neurodevelopment will still need to be assessed.{{citation needed|date=September 2023}}

Although neurological disorders do not occur, temporary symptoms of benign and familial macrocephaly include: [[Global developmental delay|developmental delay]], [[epilepsy]], and mild hypotonia.<ref name=":02" />

[[Neurodevelopment]] is assessed for all cases and suspected cases of macrocephaly to determine whether and what treatments may be needed, and whether any other syndrome/s may be present or likely to develop.{{citation needed|date=September 2023}}

=== Other forms ===
Other forms of macrocephaly include:

* Macrocephaly at birth: congenital macrocephaly already present at birth.<ref>{{Cite web |title=Macrocephaly at birth (Concept Id: C1836599) |url=https://www.ncbi.nlm.nih.gov/medgen/322956 |access-date=2024-01-16 |website=www.ncbi.nlm.nih.gov |language=en}}</ref>
* Postnatal macrocephaly: macrocephaly developed postnatally (after birth).<ref>{{Cite web |title=Postnatal macrocephaly (Concept Id: C1854417) |url=https://www.ncbi.nlm.nih.gov/medgen/340230 |access-date=2024-01-16 |website=www.ncbi.nlm.nih.gov |language=en}}</ref>
* Progressive macrocephaly: macrocephaly developed progressively over time.<ref>{{Cite web |title=Progressive macrocephaly (Concept Id: C1859896) |url=https://www.ncbi.nlm.nih.gov/medgen/395368 |access-date=2024-01-16 |website=www.ncbi.nlm.nih.gov |language=en}}</ref>
* Relative macrocephaly: mild macrocephaly measured under 2 [[Standard deviation|SD]] from mean, but larger in appearance due to other factors (ex. short stature).<ref>{{Cite web |title=Relative macrocephaly (Concept Id: C1849075) |url=https://www.ncbi.nlm.nih.gov/medgen/338607 |access-date=2024-01-16 |website=www.ncbi.nlm.nih.gov |language=en}}</ref>

== Treatment ==
Treatment varies depending on whether or not it occurs with other medical conditions in the child and where the [[cerebrospinal fluid]] is present.<ref name=":0" />
If benign and found between the brain and skull then no surgery is needed.<ref name=":0" /><ref name=":1">{{Cite web|title=Macrocephaly or "Big Head"|url=https://www.med.unc.edu/neurosurgery/services/pedsneuro/pediatric-neurosurgery-blog/macrocephaly-or-big-head/|website=Department of Neurosurgery|language=en-US|access-date=2020-04-27|archive-date=2020-08-05|archive-url=https://web.archive.org/web/20200805141844/https://www.med.unc.edu/neurosurgery/services/pedsneuro/pediatric-neurosurgery-blog/macrocephaly-or-big-head/|url-status=dead}}</ref>
If excess fluid is found between the [[Ventricular system|ventricle]] spaces in the brain then surgery will be needed.<ref name=":1" />

== Associated syndromes ==
{{Prose|section|date=March 2021}}
Below is a list of [[syndrome]]s associated with macrocephaly that are noted in ''Signs and Symptoms of Genetic Conditions: A Handbook''.<ref name=":02"/>
[[File:Lujan.jpg|thumb|[[Lujan–Fryns syndrome]]]]

=== Include multiple major and or minor anomalies ===
* [[Acrocallosal syndrome]]
* [[Apert syndrome]]
* [[Bannayan–Riley–Ruvalcaba syndrome]]
* [[Cardiofaciocutaneous syndrome]]
* [[Chromosome 14 - maternal disomy]]
* [[Chromosome 22qter deletion]]
* [[Cleidocranial dysostosis]]
* [[Costello syndrome]]
* [[Encephalocraniocutaneous lipomatosis]]
* [[FG syndrome]]
* [[Hallermann–Streiff syndrome]]
* [[Hydrolethalus syndrome]]
* [[Hypomelanosis syndrome]]
* [[Hypomelanosis of Ito]]
* [[Kelvin Peter anomaly plus syndrome]]
* [[Lujan–Fryns syndrome]]
* [[Macrocephaly-CM (MCAP)]]
* [[Marshall–Smith syndrome]]
* [[Neuhauser megalocornea/MR syndrome]]
* [[Neurofibromatosis type I]]
* [[Nevoid basal-cell carcinoma syndrome]]
* [[Noonan syndrome]]
* [[Ocular-ectodermal syndrome]]
* [[Osteopathia striata - cranial sclerosis]]
* [[Perlman syndrome]]
* [[Robinow syndrome]]
* [[Simpson–Golabi–Behmel syndrome]]
* [[Sotos syndrome]]
* [[Sturge–Weber syndrome]]
* [[Weaver syndrome]]
* [[Wiedemann–Rautenstrauch syndrome]]
* [[3C syndrome]]

[[File:Boomerang splenial infarct.jpg|thumb|[[Sturge–Weber syndrome]]]]

=== Secondary to a metabolic disorder ===
* [[Glutaric aciduria type II]]
* [[GM1 gangliosidoses|GM1 gangliosidosis]]
* [[Hunter syndrome]]
* [[Hurler syndrome]]
* [[MPS VII]]
* [[Sanfilippo syndrome]]
* [[Zellweger syndrome]]

[[File:Alexander autopsy.jpg|thumb|[[Alexander disease]]]]

=== Associated with a skeletal dysplasia ===
* [[Achondroplasia]]
* [[Campomelic dysplasia]]
* [[Craniodiaphyseal dysplasia]]
* [[Craniometaphyseal dysplasia]]
* [[Hypochondrogenesis]]
* [[Hypochondroplasia]]
* [[Kenny-Caffey syndrome]]
* [[Kniest dysplasia]]
* [[Lenz–Majewski syndrome]]
* [[Osteogenesis imperfecta III]]
* [[Osteopetrosis, autosomal recessive form]]
* [[Schneckenbecken dysplasia]]
* [[Sclerosteosis]]
* [[Short rib syndrome]], [[beemer-langer type]]
* [[Short rib-polydactyly 2 (majewski type)]]
* [[Spondyloepiphyseal dysplasia congenita]]
* [[Thanatophoric dysplasia]]

[[File:Tay-sachsUMich.jpg|thumb|[[Tay–Sachs disease]]]]

=== With no obvious physical findings ===
* [[Alexander disease]]
* [[Canavan disease]]
* [[Cobalamin deficiency]] (combined [[Methylmalonic acidemia|methylmalonic aciduria]] and [[homocystinuria]])
* [[Dandy–Walker malformation]]
* [[Glutaric aciduria type 1]]
* [[L-2-hydroxyglutaric aciduria]]
* [[Megalencephalic leukoencephalopathy with subcortical cysts]]
* [[Osteogenesis imperfecta IV]]
* [[Osteopathia striata-cranial sclerosis]]
* [[Periventricular heterotopia]]
* [[Sandhoff disease]]
* [[Tay–Sachs disease]]

==See also==
* [[Microcephaly]]
* [[Megalencephaly]]
* [[Hydrocephalus]]

==References==
{{Reflist}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=phts  GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)]
* [https://www.ncbi.nlm.nih.gov/books/NBK61984/  GeneReviews/NCBI/NIH/UW entry on 9q22.3 Microdeletion]
{{Medical resources
| DiseasesDB      = 22519
| ICD11           = {{ICD11|LB70.3}}
| ICD10           = {{ICD10|Q|75|3|q|65}}
| ICD9            = {{ICD9|756.0}}
| ICDO            =
| OMIM            = 248000
| MedlinePlus     = 003305
| eMedicineSubj   =
| eMedicineTopic  =
| MeshID          = D058627
| SNOMED CT       = 9740002
}}

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

[[Category:Congenital disorders of musculoskeletal system]]