{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:37:20Z","timestamp":1791668240832,"version":"4.3.4"},"reference-count":252,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Macrocephaly affects up to 5% of the pediatric population and is defined as an abnormally large head with an occipitofrontal circumference (OFC) &amp;gt;2 standard deviations (SD) above the mean for a given age and sex. Taking into account that about 2\u20133% of the healthy population has an OFC between 2 and 3 SD, macrocephaly is considered as \u201cclinically relevant\u201d when OFC is above 3 SD. This implies the urgent need for a diagnostic workflow to use in the clinical setting to dissect the several causes of increased OFC, from the benign form of familial macrocephaly and the Benign enlargement of subarachnoid spaces (BESS) to many pathological conditions, including genetic disorders. Moreover, macrocephaly should be differentiated by megalencephaly (MEG), which refers exclusively to brain overgrowth, exceeding twice the SD (3SD\u2014\u201cclinically relevant\u201d megalencephaly). While macrocephaly can be isolated and benign or may be the first indication of an underlying congenital, genetic, or acquired disorder, megalencephaly is most likely due to a genetic cause. Apart from the head size evaluation, a detailed family and personal history, neuroimaging, and a careful clinical evaluation are crucial to reach the correct diagnosis. In this review, we seek to underline the clinical aspects of macrocephaly and megalencephaly, emphasizing the main differential diagnosis with a major focus on common genetic disorders. We thus provide a clinico-radiological algorithm to guide pediatricians in the assessment of children with macrocephaly.<\/jats:p>","DOI":"10.3389\/fped.2021.794069","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T01:00:00Z","timestamp":1642122000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":57,"title":["Diagnostic Approach to Macrocephaly in Children"],"prefix":"10.3389","volume":"9","author":[{"given":"Andrea","family":"Accogli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Filipa","family":"Geraldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Piccolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganna","family":"Balagura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Salpietro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Madia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Maghnie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Tortora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasavina","family":"Severino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Capra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"B1","first-page":"564","article-title":"Children with macrocrania: clinical and imaging predictors of disorders requiring surgery","volume":"22","author":"Medina","year":"2001","journal-title":"Am J Neuroradiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1097\/RMR.0000000000000170","article-title":"Macrocephaly: solving the diagnostic dilemma","volume":"27","author":"Tan","year":"2018","journal-title":"Top Magn Reson Imaging."},{"key":"B3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1542\/peds.41.1.106","article-title":"Head circumference from birth to eighteen years","volume":"41","author":"Nellhaus","year":"1968","journal-title":"Pediatrics."},{"key":"B4","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/0887-8994(86)90072-X","article-title":"Megalencephaly: types, clinical syndromes, and management","volume":"2","author":"DeMyer","year":"1986","journal-title":"Pediatr Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.1093\/brain\/awaa174","article-title":"Definitions and classification of malformations of cortical development: practical guidelines","volume":"143","author":"Severino","year":"2020","journal-title":"Brain."},{"key":"B6","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1111\/ped.13543","article-title":"Macrocephaly diagnosed during well child visits","volume":"60","author":"Yilmazba\u015f","year":"2018","journal-title":"Pediatr Int."},{"key":"B7","doi-asserted-by":"publisher","first-page":"267","DOI":"10.31887\/dcns.2018.20.4\/gmirzaa","article-title":"From microcephaly to megalencephaly: determinants of brain size","volume":"20","author":"Pirozzi","year":"2018","journal-title":"Dialogues Clin Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1002\/ajmg.a.32434","article-title":"Genetic disorders associated with macrocephaly","volume":"146","author":"Williams","year":"2008","journal-title":"Am J Med Genet A."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0387-7604(88)80037-8","article-title":"W Hanlo P. 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