{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T13:55:11Z","timestamp":1768917311658,"version":"3.49.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"13","license":[{"start":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:00:00Z","timestamp":1665187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:00:00Z","timestamp":1665187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Radiol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Overgrowth syndromes can manifest with enlargement of the brain and other body parts and are associated with malignancy. Much of the current literature focuses on the imaging findings of the somatic overgrowth, while there is relatively little describing the overgrowth of the central nervous system. In this pictorial essay, we discuss common syndromes with central nervous system overgrowth, highlight key imaging features, and review the underlying genetics, including the PI3K-AKT-mTOR pathway as well as other syndromes from various genes.<\/jats:p>","DOI":"10.1007\/s00247-022-05408-5","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:03:41Z","timestamp":1665187421000},"page":"2452-2466","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neuroimaging features of genetic syndromes associated with CNS overgrowth"],"prefix":"10.1007","volume":"52","author":[{"given":"Anthony R.","family":"Zamary","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6689-8912","authenticated-orcid":false,"given":"Mark D.","family":"Mamlouk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,8]]},"reference":[{"key":"5408_CR1","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/s41574-019-0180-z","volume":"15","author":"F Brioude","year":"2019","unstructured":"Brioude F, Toutain A, Giabicani E et al (2019) Overgrowth syndromes - clinical and molecular aspects and tumour risk. Nat Rev Endocrinol 15:299\u2013311","journal-title":"Nat Rev Endocrinol"},{"key":"5408_CR2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1159\/000484532","volume":"9","author":"B Kamien","year":"2018","unstructured":"Kamien B, Ronan A, Poke G et al (2018) A clinical review of generalized overgrowth syndromes in the era of massively parallel sequencing. Mol Syndromol 9:70\u201382","journal-title":"Mol Syndromol"},{"key":"5408_CR3","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.1093\/brain\/awaa174","volume":"143","author":"M Severino","year":"2020","unstructured":"Severino M, Geraldo AF, Utz N et al (2020) Definitions and classification of malformations of cortical development: practical guidelines. Brain 143:2874\u20132894","journal-title":"Brain"},{"key":"5408_CR4","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1148\/rg.2019180136","volume":"39","author":"F Bertino","year":"2019","unstructured":"Bertino F, Braithwaite KA, Hawkins CM et al (2019) Congenital limb overgrowth syndromes associated with vascular anomalies. Radiographics 39:491\u2013515","journal-title":"Radiographics"},{"key":"5408_CR5","volume-title":"GeneReviews","author":"G Mirzaa","year":"2013","unstructured":"Mirzaa G, Graham JM Jr, Keppler-Noreuil K (2013) PIK3CA-related overgrowth spectrum. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews. University of Washington, Seattle"},{"key":"5408_CR6","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41586-018-0217-9","volume":"558","author":"Q Venot","year":"2018","unstructured":"Venot Q, Blanc T, Rabia SH et al (2018) Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature 558:540\u2013546","journal-title":"Nature"},{"key":"5408_CR7","doi-asserted-by":"publisher","first-page":"e87623","DOI":"10.1172\/jci.insight.87623","volume":"1","author":"G Mirzaa","year":"2016","unstructured":"Mirzaa G, Timms AE, Conti V et al (2016) PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution. JCI Insight 1:e87623","journal-title":"JCI Insight"},{"key":"5408_CR8","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.3174\/ajnr.A2349","volume":"32","author":"AI Alomari","year":"2011","unstructured":"Alomari AI, Chaudry G, Rodesch G et al (2011) Complex spinal-paraspinal fast-flow lesions in CLOVES syndrome: analysis of clinical and imaging findings in 6 patients. AJNR Am J Neuroradiol 32:1812\u20131817","journal-title":"AJNR Am J Neuroradiol"},{"key":"5408_CR9","unstructured":"Mirzaa G, Conway R, Graham JM Jr, Dobyns WB (1993\u20132019) PIK3CA-related segmental overgrowth. In: Adam MP, Ardinger HH, Pagon RA et al (eds). GeneReviews. University of Washington, Seattle"},{"key":"5408_CR10","doi-asserted-by":"publisher","unstructured":"Peterman CM, Fevurly RD, Alomari AI et al (2017) Sonographic screening for Wilms tumor in children with CLOVES syndrome. Pediatr Blood Cancer\u00a064:e26684. https:\/\/doi.org\/10.1002\/pbc.26684","DOI":"10.1002\/pbc.26684"},{"key":"5408_CR11","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/ajmg.a.34402","volume":"158a","author":"GM Mirzaa","year":"2012","unstructured":"Mirzaa GM, Conway RL, Gripp KW et al (2012) Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. Am J Med Genet A 158a:269\u2013291","journal-title":"Am J Med Genet A"},{"key":"5408_CR12","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1007\/s00381-021-05222-8","volume":"37","author":"M Alamar","year":"2021","unstructured":"Alamar M, Candela S, Flor-Goikoetxea A et al (2021) Megalencephaly-capillary malformation syndrome and associated hydrocephalus: treatment options and revision of the literature. Childs Nerv Syst 37:2441\u20132449","journal-title":"Childs Nerv Syst"},{"key":"5408_CR13","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1002\/ajmg.a.32040","volume":"143a","author":"RL Conway","year":"2007","unstructured":"Conway RL, Pressman BD, Dobyns WB et al (2007) Neuroimaging findings in macrocephaly-capillary malformation: a longitudinal study of 17 patients. Am J Med Genet A 143a:2981\u20133008","journal-title":"Am J Med Genet A"},{"key":"5408_CR14","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s13023-020-01480-y","volume":"15","author":"HJ Park","year":"2020","unstructured":"Park HJ, Shin CH, Yoo WJ et al (2020) Detailed analysis of phenotypes and genotypes in megalencephaly-capillary malformation-polymicrogyria syndrome caused by somatic mosaicism of PIK3CA mutations. Orphanet J Rare Dis 15:205","journal-title":"Orphanet J Rare Dis"},{"key":"5408_CR15","doi-asserted-by":"publisher","first-page":"844","DOI":"10.3390\/cancers11060844","volume":"11","author":"R Pilarski","year":"2019","unstructured":"Pilarski R (2019) PTEN hamartoma tumor syndrome: a clinical overview. Cancers (Basel) 11:844","journal-title":"Cancers (Basel)"},{"key":"5408_CR16","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1002\/ajmg.a.61532","volume":"182","author":"T Shiohama","year":"2020","unstructured":"Shiohama T, Levman J, Vasung L, Takahashi E (2020) Brain morphological analysis in PTEN hamartoma tumor syndrome. Am J Med Genet A 182:1117\u20131129","journal-title":"Am J Med Genet A"},{"key":"5408_CR17","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1038\/mp.2014.125","volume":"20","author":"TW Frazier","year":"2015","unstructured":"Frazier TW, Embacher R, Tilot AK et al (2015) Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism. Mol Psychiatry 20:1132\u20131138","journal-title":"Mol Psychiatry"},{"key":"5408_CR18","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1097\/RCT.0000000000000814","volume":"43","author":"R Dhamija","year":"2019","unstructured":"Dhamija R, Wood CP, Porter AB et al (2019) Updated imaging features of dysplastic cerebellar gangliocytoma. J Comput Assist Tomogr 43:277\u2013281","journal-title":"J Comput Assist Tomogr"},{"key":"5408_CR19","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1212\/CPJ.0000000000000463","volume":"8","author":"R Dhamija","year":"2018","unstructured":"Dhamija R, Weindling SM, Porter AB et al (2018) Neuroimaging abnormalities in patients with Cowden syndrome: retrospective single-center study. Neurol Clin Pract 8:207\u2013213","journal-title":"Neurol Clin Pract"},{"key":"5408_CR20","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1097\/01.md.0000158792.24888.d2","volume":"84","author":"C Lok","year":"2005","unstructured":"Lok C, Viseux V, Avril MF et al (2005) Brain magnetic resonance imaging in patients with Cowden syndrome. Medicine (Baltimore) 84:129\u2013136","journal-title":"Medicine (Baltimore)"},{"key":"5408_CR21","first-page":"e011","volume":"2","author":"LRS Hill","year":"2021","unstructured":"Hill LRS, Duis J, Kulungowski AM et al (2021) A challenging diagnosis: PTEN hamartoma tumor syndrome presenting as isolated soft-tissue vascular anomalies. JOVA 2:e011","journal-title":"JOVA"},{"key":"5408_CR22","volume-title":"GeneReviews","author":"L Yehia","year":"1993","unstructured":"Yehia L, Eng C (1993) PTEN hamartoma tumor syndrome. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews. University of Washington, Seattle"},{"key":"5408_CR23","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3174\/ajnr.A3680","volume":"35","author":"R Bhargava","year":"2014","unstructured":"Bhargava R, Au Yong KJ, Leonard N (2014) Bannayan-Riley-Ruvalcaba syndrome: MRI neuroimaging features in a series of 7 patients. AJNR Am J Neuroradiol 35:402\u2013406","journal-title":"AJNR Am J Neuroradiol"},{"key":"5408_CR24","volume-title":"GeneReviews","author":"LG Biesecker","year":"1993","unstructured":"Biesecker LG, Sapp JC (1993) Proteus syndrome. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews. University of Washington, Seattle"},{"key":"5408_CR25","first-page":"41","volume":"56","author":"LG Biesecker","year":"2018","unstructured":"Biesecker LG (2018) Myths and misdiagnoses of Proteus Ssyndrome. Asian J Anesthesiol 56:41\u201341","journal-title":"Asian J Anesthesiol"},{"key":"5408_CR26","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1056\/NEJMoa1104017","volume":"365","author":"MJ Lindhurst","year":"2011","unstructured":"Lindhurst MJ, Sapp JC, Teer JK et al (2011) A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med 365:611\u2013619","journal-title":"N Engl J Med"},{"key":"5408_CR27","doi-asserted-by":"publisher","first-page":"794069","DOI":"10.3389\/fped.2021.794069","volume":"9","author":"A Accogli","year":"2022","unstructured":"Accogli A, Geraldo AF, Piccolo G et al (2022) Diagnostic approach to macrocephaly in children. Front Pediatr 9:794069","journal-title":"Front Pediatr"},{"key":"5408_CR28","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.neuron.2012.03.010","volume":"74","author":"A Poduri","year":"2012","unstructured":"Poduri A, Evrony GD, Cai X et al (2012) Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron 74:41\u201348","journal-title":"Neuron"},{"key":"5408_CR29","doi-asserted-by":"publisher","first-page":"574857","DOI":"10.3389\/fped.2020.574857","volume":"8","author":"J Manor","year":"2020","unstructured":"Manor J, Lalani SR (2020) Overgrowth syndromes\u2014evaluation, diagnosis, and management. Front Pediatr 8:574857","journal-title":"Front Pediatr"},{"key":"5408_CR30","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1086\/432082","volume":"77","author":"K Tatton-Brown","year":"2005","unstructured":"Tatton-Brown K, Douglas J, Coleman K et al (2005) Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet 77:193\u2013204","journal-title":"Am J Hum Genet"},{"key":"5408_CR31","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1111\/j.1528-1167.2012.03418.x","volume":"53","author":"F Nicita","year":"2012","unstructured":"Nicita F, Ruggieri M, Polizzi A et al (2012) Seizures and epilepsy in Sotos syndrome: analysis of 19 Caucasian patients with long-term follow-up. Epilepsia 53:e102\u2013e105","journal-title":"Epilepsia"},{"key":"5408_CR32","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/(SICI)1096-8628(19970211)68:4<462::AID-AJMG18>3.0.CO;2-Q","volume":"68","author":"GB Schaefer","year":"1997","unstructured":"Schaefer GB, Bodensteiner JB, Buehler BA et al (1997) The neuroimaging findings in Sotos syndrome. Am J Med Genet 68:462\u2013465","journal-title":"Am J Med Genet"},{"key":"5408_CR33","first-page":"1","volume":"52","author":"S Tei","year":"2006","unstructured":"Tei S, Tsuneishi S, Matsuo M (2006) The first Japanese familial Sotos syndrome with a novel mutation of the NSD1 gene. Kobe J Med Sci 52:1\u20138","journal-title":"Kobe J Med Sci"},{"key":"5408_CR34","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.1002\/ajmg.a.36229","volume":"161a","author":"K Tatton-Brown","year":"2013","unstructured":"Tatton-Brown K, Murray A, Hanks S et al (2013) Weaver syndrome and EZH2 mutations: clarifying the clinical phenotype. Am J Med Genet A 161a:2972\u20132980","journal-title":"Am J Med Genet A"},{"key":"5408_CR35","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1002\/ajmg.a.35358","volume":"158a","author":"K Gardiner","year":"2012","unstructured":"Gardiner K, Chitayat D, Choufani S et al (2012) Brain abnormalities in patients with Beckwith-Wiedemann syndrome. Am J Med Genet A 158a:1388\u20131394","journal-title":"Am J Med Genet A"}],"container-title":["Pediatric Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00247-022-05408-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00247-022-05408-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00247-022-05408-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T13:13:46Z","timestamp":1669641226000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00247-022-05408-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,8]]},"references-count":35,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["5408"],"URL":"https:\/\/doi.org\/10.1007\/s00247-022-05408-5","relation":{},"ISSN":["0301-0449","1432-1998"],"issn-type":[{"value":"0301-0449","type":"print"},{"value":"1432-1998","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,8]]},"assertion":[{"value":"24 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}