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Brain malformation

MedGen UID:
82742
•Concept ID:
C0266449
•
Congenital Abnormality
Synonym: Brain malformations
SNOMED CT: Congenital brain anomaly (57148006); Congenital anomaly of brain (57148006); Deformity of brain (57148006)
 
Orphanet: ORPHA199633

Definition

Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it to develop abnormally. Sometimes it''s a genetic problem. In other cases, exposure to certain medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, abnormally small or large, or not fully developed.CHAR(13) Treatment depends upon the problem. In many cases, treatment only helps with symptoms. It may include antiseizure medicines, shunts to drain fluid from the brain, and physical therapy.CHAR(13) There are head malformations that do not involve the brain. Craniofacial disorders are the result of abnormal growth of soft tissue and bones in the face and head. It''s common for new babies to have slightly uneven heads, but parents should watch the shape of their baby''s head for possible problems.CHAR(13) NIH: National Institute of Neurological Disorders and StrokeCHAR(13) [from MedlinePlus]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBrain malformation

Professional guidelines

PubMed

ACR Appropriateness Criteria® Ataxia-Child.
Expert Panel on Pediatric Imaging, Radhakrishnan R, Shea LAG, Pruthi S, Silvera VM, Bosemani T, Desai NK, Gilbert DL, Glenn OA, Guimaraes CV, Ho ML, Lam HFS, Maheshwari M, Mirsky DM, Nadel HR, Partap S, Schooler GR, Udayasankar UK, Whitehead MT, Wright JN, Rigsby CK
J Am Coll Radiol 2022 Nov;19(11S):S240-S255. doi: 10.1016/j.jacr.2022.09.010. PMID: 36436955
Genetic counseling and "molecular" prenatal diagnosis of holoprosencephaly (HPE).
Mercier S, Dubourg C, Belleguic M, Pasquier L, Loget P, Lucas J, Bendavid C, Odent S
Am J Med Genet C Semin Med Genet 2010 Feb 15;154C(1):191-6. doi: 10.1002/ajmg.c.30246. PMID: 20104616
Evaluation and management of children with holoprosencephaly.
Hahn JS, Plawner LL
Pediatr Neurol 2004 Aug;31(2):79-88. doi: 10.1016/j.pediatrneurol.2004.03.006. PMID: 15301825

Recent clinical studies

Etiology

The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR, PIK3CA, and PIK3R2.
Lai A, Soucy A, El Achkar CM, Barkovich AJ, Cao Y, DiStefano M, Evenson M, Guerrini R, Knight D, Lee YS, Mefford HC, Miller DT, Mirzaa G, Mochida G, Rodan LH, Patel M, Smith L, Spencer S, Walsh CA, Yang E, Yuskaitis CJ, Yu T, Poduri A; ClinGen Brain Malformation Variant Curation Expert Panel
Genet Med 2022 Nov;24(11):2240-2248. Epub 2022 Aug 23 doi: 10.1016/j.gim.2022.07.020. PMID: 35997716Free PMC Article
Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome.
Stephenson SEM, Costain G, Blok LER, Silk MA, Nguyen TB, Dong X, Alhuzaimi DE, Dowling JJ, Walker S, Amburgey K, Hayeems RZ, Rodan LH, Schwartz MA, Picker J, Lynch SA, Gupta A, Rasmussen KJ, Schimmenti LA, Klee EW, Niu Z, Agre KE, Chilton I, Chung WK, Revah-Politi A, Au PYB, Griffith C, Racobaldo M, Raas-Rothschild A, Ben Zeev B, Barel O, Moutton S, Morice-Picard F, Carmignac V, Cornaton J, Marle N, Devinsky O, Stimach C, Wechsler SB, Hainline BE, Sapp K, Willems M, Bruel AL, Dias KR, Evans CA, Roscioli T, Sachdev R, Temple SEL, Zhu Y, Baker JJ, Scheffer IE, Gardiner FJ, Schneider AL, Muir AM, Mefford HC, Crunk A, Heise EM, Millan F, Monaghan KG, Person R, Rhodes L, Richards S, Wentzensen IM, Cogné B, Isidor B, Nizon M, Vincent M, Besnard T, Piton A, Marcelis C, Kato K, Koyama N, Ogi T, Goh ES, Richmond C, Amor DJ, Boyce JO, Morgan AT, Hildebrand MS, Kaspi A, Bahlo M, Friðriksdóttir R, Katrínardóttir H, Sulem P, Stefánsson K, Björnsson HT, Mandelstam S, Morleo M, Mariani M; TUDP Study Group, Scala M, Accogli A, Torella A, Capra V, Wallis M, Jansen S, Weisfisz Q, de Haan H, Sadedin S; Broad Center for Mendelian Genomics, Lim SC, White SM, Ascher DB, Schenck A, Lockhart PJ, Christodoulou J, Tan TY
Am J Hum Genet 2022 Apr 7;109(4):601-617. doi: 10.1016/j.ajhg.2022.03.002. PMID: 35395208Free PMC Article
Neurocutaneous melanocytosis (melanosis).
Ruggieri M, Polizzi A, Catanzaro S, Bianco ML, Praticò AD, Di Rocco C
Childs Nerv Syst 2020 Oct;36(10):2571-2596. Epub 2020 Oct 13 doi: 10.1007/s00381-020-04770-9. PMID: 33048248
Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders.
Fischer-Zirnsak B, Segebrecht L, Schubach M, Charles P, Alderman E, Brown K, Cadieux-Dion M, Cartwright T, Chen Y, Costin C, Fehr S, Fitzgerald KM, Fleming E, Foss K, Ha T, Hildebrand G, Horn D, Liu S, Marco EJ, McDonald M, McWalter K, Race S, Rush ET, Si Y, Saunders C, Slavotinek A, Stockler-Ipsiroglu S, Telegrafi A, Thiffault I, Torti E, Tsai AC, Wang X, Zafar M, Keren B, Kornak U, Boerkoel CF, Mirzaa G, Ehmke N
Am J Hum Genet 2019 Sep 5;105(3):631-639. Epub 2019 Jul 25 doi: 10.1016/j.ajhg.2019.07.002. PMID: 31353024Free PMC Article
Spina bifida.
Copp AJ, Adzick NS, Chitty LS, Fletcher JM, Holmbeck GN, Shaw GM
Nat Rev Dis Primers 2015 Apr 30;1:15007. doi: 10.1038/nrdp.2015.7. PMID: 27189655Free PMC Article

Diagnosis

Neurocutaneous melanocytosis (melanosis).
Ruggieri M, Polizzi A, Catanzaro S, Bianco ML, Praticò AD, Di Rocco C
Childs Nerv Syst 2020 Oct;36(10):2571-2596. Epub 2020 Oct 13 doi: 10.1007/s00381-020-04770-9. PMID: 33048248
Rhombencephalosynapsis: Fused cerebellum, confused geneticists.
Aldinger KA, Dempsey JC, Tully HM, Grout ME, Mehaffey MG, Dobyns WB, Doherty D
Am J Med Genet C Semin Med Genet 2018 Dec;178(4):432-439. doi: 10.1002/ajmg.c.31666. PMID: 30580482Free PMC Article
Genetics of cerebellar disorders.
Valente EM, Nuovo S, Doherty D
Handb Clin Neurol 2018;154:267-286. doi: 10.1016/B978-0-444-63956-1.00016-3. PMID: 29903444
Spina bifida.
Copp AJ, Adzick NS, Chitty LS, Fletcher JM, Holmbeck GN, Shaw GM
Nat Rev Dis Primers 2015 Apr 30;1:15007. doi: 10.1038/nrdp.2015.7. PMID: 27189655Free PMC Article
Holoprosencephaly.
Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V
Orphanet J Rare Dis 2007 Feb 2;2:8. doi: 10.1186/1750-1172-2-8. PMID: 17274816Free PMC Article

Therapy

Hemispheric epilepsy surgery for hemimegalencephaly: The UCLA experience.
Goel K, Phillips HW, Chen JS, Ngo J, Edmonds B, Ha PX, Wang A, Weil A, Russell BE, Salamon N, Nariai H, Fallah A
Epilepsia 2024 Jan;65(1):57-72. Epub 2023 Nov 11 doi: 10.1111/epi.17807. PMID: 37873610
Levetiracetam versus Phenobarbital for Neonatal Seizures: A Retrospective Cohort Study.
Bättig L, Dünner C, Cserpan D, Rüegger A, Hagmann C, Schmitt B, Pisani F, Ramantani G
Pediatr Neurol 2023 Jan;138:62-70. Epub 2022 Oct 22 doi: 10.1016/j.pediatrneurol.2022.10.004. PMID: 36401982
Atypical psychotic symptoms and Dandy-Walker variant.
Williams AJ, Wang Z, Taylor SF
Neurocase 2016 Oct;22(5):472-475. Epub 2016 Sep 23 doi: 10.1080/13554794.2016.1237657. PMID: 27662527
Spina bifida.
Copp AJ, Adzick NS, Chitty LS, Fletcher JM, Holmbeck GN, Shaw GM
Nat Rev Dis Primers 2015 Apr 30;1:15007. doi: 10.1038/nrdp.2015.7. PMID: 27189655Free PMC Article
A review of the neuroanatomical findings in children with fetal alcohol syndrome or prenatal exposure to alcohol.
Roebuck TM, Mattson SN, Riley EP
Alcohol Clin Exp Res 1998 Apr;22(2):339-44. doi: 10.1111/j.1530-0277.1998.tb03658.x. PMID: 9581638

Prognosis

Variants in PTEN Are Associated With a Diverse Spectrum of Cortical Dysplasia.
Shelkowitz E, Stence NV, Neuberger I, Park KL, Saenz MS, Pao E, Oyama N, Friedman SD, Shaw DWW, Mirzaa GM
Pediatr Neurol 2023 Oct;147:154-162. Epub 2023 Jun 22 doi: 10.1016/j.pediatrneurol.2023.06.015. PMID: 37619436
Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome.
Stephenson SEM, Costain G, Blok LER, Silk MA, Nguyen TB, Dong X, Alhuzaimi DE, Dowling JJ, Walker S, Amburgey K, Hayeems RZ, Rodan LH, Schwartz MA, Picker J, Lynch SA, Gupta A, Rasmussen KJ, Schimmenti LA, Klee EW, Niu Z, Agre KE, Chilton I, Chung WK, Revah-Politi A, Au PYB, Griffith C, Racobaldo M, Raas-Rothschild A, Ben Zeev B, Barel O, Moutton S, Morice-Picard F, Carmignac V, Cornaton J, Marle N, Devinsky O, Stimach C, Wechsler SB, Hainline BE, Sapp K, Willems M, Bruel AL, Dias KR, Evans CA, Roscioli T, Sachdev R, Temple SEL, Zhu Y, Baker JJ, Scheffer IE, Gardiner FJ, Schneider AL, Muir AM, Mefford HC, Crunk A, Heise EM, Millan F, Monaghan KG, Person R, Rhodes L, Richards S, Wentzensen IM, Cogné B, Isidor B, Nizon M, Vincent M, Besnard T, Piton A, Marcelis C, Kato K, Koyama N, Ogi T, Goh ES, Richmond C, Amor DJ, Boyce JO, Morgan AT, Hildebrand MS, Kaspi A, Bahlo M, Friðriksdóttir R, Katrínardóttir H, Sulem P, Stefánsson K, Björnsson HT, Mandelstam S, Morleo M, Mariani M; TUDP Study Group, Scala M, Accogli A, Torella A, Capra V, Wallis M, Jansen S, Weisfisz Q, de Haan H, Sadedin S; Broad Center for Mendelian Genomics, Lim SC, White SM, Ascher DB, Schenck A, Lockhart PJ, Christodoulou J, Tan TY
Am J Hum Genet 2022 Apr 7;109(4):601-617. doi: 10.1016/j.ajhg.2022.03.002. PMID: 35395208Free PMC Article
The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy.
Hebebrand M, Hüffmeier U, Trollmann R, Hehr U, Uebe S, Ekici AB, Kraus C, Krumbiegel M, Reis A, Thiel CT, Popp B
Orphanet J Rare Dis 2019 Feb 11;14(1):38. doi: 10.1186/s13023-019-1020-x. PMID: 30744660Free PMC Article
The genetics of cerebellar malformations.
Aldinger KA, Doherty D
Semin Fetal Neonatal Med 2016 Oct;21(5):321-32. Epub 2016 May 7 doi: 10.1016/j.siny.2016.04.008. PMID: 27160001Free PMC Article
Holoprosencephaly.
Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V
Orphanet J Rare Dis 2007 Feb 2;2:8. doi: 10.1186/1750-1172-2-8. PMID: 17274816Free PMC Article

Clinical prediction guides

Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome.
Stephenson SEM, Costain G, Blok LER, Silk MA, Nguyen TB, Dong X, Alhuzaimi DE, Dowling JJ, Walker S, Amburgey K, Hayeems RZ, Rodan LH, Schwartz MA, Picker J, Lynch SA, Gupta A, Rasmussen KJ, Schimmenti LA, Klee EW, Niu Z, Agre KE, Chilton I, Chung WK, Revah-Politi A, Au PYB, Griffith C, Racobaldo M, Raas-Rothschild A, Ben Zeev B, Barel O, Moutton S, Morice-Picard F, Carmignac V, Cornaton J, Marle N, Devinsky O, Stimach C, Wechsler SB, Hainline BE, Sapp K, Willems M, Bruel AL, Dias KR, Evans CA, Roscioli T, Sachdev R, Temple SEL, Zhu Y, Baker JJ, Scheffer IE, Gardiner FJ, Schneider AL, Muir AM, Mefford HC, Crunk A, Heise EM, Millan F, Monaghan KG, Person R, Rhodes L, Richards S, Wentzensen IM, Cogné B, Isidor B, Nizon M, Vincent M, Besnard T, Piton A, Marcelis C, Kato K, Koyama N, Ogi T, Goh ES, Richmond C, Amor DJ, Boyce JO, Morgan AT, Hildebrand MS, Kaspi A, Bahlo M, Friðriksdóttir R, Katrínardóttir H, Sulem P, Stefánsson K, Björnsson HT, Mandelstam S, Morleo M, Mariani M; TUDP Study Group, Scala M, Accogli A, Torella A, Capra V, Wallis M, Jansen S, Weisfisz Q, de Haan H, Sadedin S; Broad Center for Mendelian Genomics, Lim SC, White SM, Ascher DB, Schenck A, Lockhart PJ, Christodoulou J, Tan TY
Am J Hum Genet 2022 Apr 7;109(4):601-617. doi: 10.1016/j.ajhg.2022.03.002. PMID: 35395208Free PMC Article
The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy.
Hebebrand M, Hüffmeier U, Trollmann R, Hehr U, Uebe S, Ekici AB, Kraus C, Krumbiegel M, Reis A, Thiel CT, Popp B
Orphanet J Rare Dis 2019 Feb 11;14(1):38. doi: 10.1186/s13023-019-1020-x. PMID: 30744660Free PMC Article
MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance.
Dobyns WB, Aldinger KA, Ishak GE, Mirzaa GM, Timms AE, Grout ME, Dremmen MHG, Schot R, Vandervore L, van Slegtenhorst MA, Wilke M, Kasteleijn E, Lee AS, Barry BJ, Chao KR, Szczałuba K, Kobori J, Hanson-Kahn A, Bernstein JA, Carr L, D'Arco F, Miyana K, Okazaki T, Saito Y, Sasaki M, Das S, Wheeler MM, Bamshad MJ, Nickerson DA; University of Washington Center for Mendelian Genomics; Center for Mendelian Genomics at the Broad Institute of MIT and Harvard, Engle EC, Verheijen FW, Doherty D, Mancini GMS
Am J Hum Genet 2018 Dec 6;103(6):1009-1021. Epub 2018 Nov 21 doi: 10.1016/j.ajhg.2018.10.019. PMID: 30471716Free PMC Article
Neuropathology of holoprosencephaly.
Marcorelles P, Laquerriere A
Am J Med Genet C Semin Med Genet 2010 Feb 15;154C(1):109-19. doi: 10.1002/ajmg.c.30249. PMID: 20104606
Holoprosencephaly.
Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V
Orphanet J Rare Dis 2007 Feb 2;2:8. doi: 10.1186/1750-1172-2-8. PMID: 17274816Free PMC Article

Recent systematic reviews

Automatic Detection of Focal Cortical Dysplasia Using MRI: A Systematic Review.
Jiménez-Murillo D, Castro-Ospina AE, Duque-Muñoz L, Martínez-Vargas JD, Suárez-Revelo JX, Vélez-Arango JM, de la Iglesia-Vayá M
Sensors (Basel) 2023 Aug 10;23(16) doi: 10.3390/s23167072. PMID: 37631608Free PMC Article
Neuropsychological profile of agenesis of the corpus callosum: a systematic review.
Siffredi V, Anderson V, Leventer RJ, Spencer-Smith MM
Dev Neuropsychol 2013;38(1):36-57. doi: 10.1080/87565641.2012.721421. PMID: 23311314

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