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Lissencephaly with cerebellar hypoplasia

MedGen UID:
905529
•Concept ID:
C4274995
•
Disease or Syndrome
Synonyms: LCH; Lissencephaly co-occurrent with congenital cerebellar hypoplasia; lissencephaly with cerebellar hypoplasia
SNOMED CT: Lissencephaly co-occurrent with congenital cerebellar hypoplasia (715817007); Lissencephaly with cerebellar hypoplasia (715817007)
 
Monarch Initiative: MONDO:0019450
Orphanet: ORPHA86823

Definition

Lissencephaly with cerebellar hypoplasia (LCH) is a variant form of lissencephaly and involves a heterogeneous group of cortical malformations without severe congenital microcephaly (>-3 SD). LCH is characterized by cerebellar underdevelopment ranging from vermian hypoplasia to total aplasia with classical or cobblestone lissencephaly. The phenotypic features of LCH include small head circumference (between -2 and -3 standard deviations (SD) forage) at birth and postnatally, moderate to severe intellectual disability, hypotonia and spasticity. Seizures are often observed and infantile spasms have been reported in some rare cases. LCH has been classified into six subgroups according to neuroradiographic properties and are classified LCH type A to F. [from ORDO]

Professional guidelines

PubMed

Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing.
Guerrini R, Carrozzo R
Seizure 2002 Apr;11 Suppl A:532-43; quiz 544-7. PMID: 12185771
Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing.
Guerrini R, Carrozzo R
Seizure 2001 Oct;10(7):532-43; quiz 544-7. doi: 10.1053/seiz.2001.0650. PMID: 11749114

Recent clinical studies

Etiology

Tubulin mutations in human neurodevelopmental disorders.
Maillard C, Roux CJ, Charbit-Henrion F, Steffann J, Laquerriere A, Quazza F, Buisson NB
Semin Cell Dev Biol 2023 Mar 15;137:87-95. Epub 2022 Jul 30 doi: 10.1016/j.semcdb.2022.07.009. PMID: 35915025
Tubulinopathies.
Gonçalves FG, Freddi TAL, Taranath A, Lakshmanan R, Goetti R, Feltrin FS, Mankad K, Teixeira SR, Hanagandi PB, Arrigoni F
Top Magn Reson Imaging 2018 Dec;27(6):395-408. doi: 10.1097/RMR.0000000000000188. PMID: 30516692
Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with a loss-of-function mutation in CDK5.
Magen D, Ofir A, Berger L, Goldsher D, Eran A, Katib N, Nijem Y, Vlodavsky E, Tzur S, Behar DM, Fellig Y, Mandel H
Hum Genet 2015 Mar;134(3):305-14. Epub 2015 Jan 6 doi: 10.1007/s00439-014-1522-5. PMID: 25560765
Genetic malformations of cortical development.
Guerrini R, Marini C
Exp Brain Res 2006 Aug;173(2):322-33. Epub 2006 May 25 doi: 10.1007/s00221-006-0501-z. PMID: 16724181
Lissencephaly with cerebellar hypoplasia (LCH): a heterogeneous group of cortical malformations.
Ross ME, Swanson K, Dobyns WB
Neuropediatrics 2001 Oct;32(5):256-63. doi: 10.1055/s-2001-19120. PMID: 11748497

Diagnosis

Tubulin mutations in human neurodevelopmental disorders.
Maillard C, Roux CJ, Charbit-Henrion F, Steffann J, Laquerriere A, Quazza F, Buisson NB
Semin Cell Dev Biol 2023 Mar 15;137:87-95. Epub 2022 Jul 30 doi: 10.1016/j.semcdb.2022.07.009. PMID: 35915025
Seizures and EEG characteristics in a cohort of pediatric patients with dystroglycanopathies.
Yang H, Song D, Liu Y, Chen X, Zhu Y, Wei C, Fu X, Liu X, Yang Z, Xiong H
Seizure 2022 Oct;101:39-47. Epub 2022 Jul 13 doi: 10.1016/j.seizure.2022.07.008. PMID: 35863218
Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.
Abdel Razek AA, Castillo M
J Comput Assist Tomogr 2016 Jan-Feb;40(1):14-25. doi: 10.1097/RCT.0000000000000340. PMID: 26599961
Lissencephaly with brainstem and cerebellar hypoplasia and congenital cataracts.
Abumansour IS, Wrogemann J, Chudley AE, Chodirker BN, Salman MS
J Child Neurol 2014 Jun;29(6):860-4. Epub 2013 Apr 26 doi: 10.1177/0883073813485637. PMID: 23625088
Diffuse malformations of cortical development.
Bahi-Buisson N, Guerrini R
Handb Clin Neurol 2013;111:653-65. doi: 10.1016/B978-0-444-52891-9.00068-3. PMID: 23622213

Therapy

Pathogenesis of migration disorders.
Gressens P
Curr Opin Neurol 2006 Apr;19(2):135-40. doi: 10.1097/01.wco.0000218228.73678.e1. PMID: 16538086

Prognosis

Comparison of brain MRI findings with language and motor function in the dystroglycanopathies.
Brun BN, Mockler SR, Laubscher KM, Stephan CM, Wallace AM, Collison JA, Zimmerman MB, Dobyns WB, Mathews KD
Neurology 2017 Feb 14;88(7):623-629. Epub 2017 Jan 13 doi: 10.1212/WNL.0000000000003609. PMID: 28087826Free PMC Article
Congenital Zika Virus Infection: Beyond Neonatal Microcephaly.
Melo AS, Aguiar RS, Amorim MM, Arruda MB, Melo FO, Ribeiro ST, Batista AG, Ferreira T, Dos Santos MP, Sampaio VV, Moura SR, Rabello LP, Gonzaga CE, Malinger G, Ximenes R, de Oliveira-Szejnfeld PS, Tovar-Moll F, Chimelli L, Silveira PP, Delvechio R, Higa L, Campanati L, Nogueira RM, Filippis AM, Szejnfeld J, Voloch CM, Ferreira OC Jr, Brindeiro RM, Tanuri A
JAMA Neurol 2016 Dec 1;73(12):1407-1416. doi: 10.1001/jamaneurol.2016.3720. PMID: 27695855
The wide spectrum of tubulinopathies: what are the key features for the diagnosis?
Bahi-Buisson N, Poirier K, Fourniol F, Saillour Y, Valence S, Lebrun N, Hully M, Bianco CF, Boddaert N, Elie C, Lascelles K, Souville I; LIS-Tubulinopathies Consortium, Beldjord C, Chelly J
Brain 2014 Jun;137(Pt 6):1676-700. doi: 10.1093/brain/awu082. PMID: 24860126
Lissencephaly with marked ventricular dilation, agenesis of corpus callosum, and cerebellar hypoplasia caused by TUBA1A mutation.
Okumura A, Hayashi M, Tsurui H, Yamakawa Y, Abe S, Kudo T, Suzuki R, Shimizu T, Shimojima K, Yamamoto T
Brain Dev 2013 Mar;35(3):274-9. Epub 2012 May 26 doi: 10.1016/j.braindev.2012.05.006. PMID: 22633752
Location and type of mutation in the LIS1 gene do not predict phenotypic severity.
Uyanik G, Morris-Rosendahl DJ, Stiegler J, Klapecki J, Gross C, Berman Y, Martin P, Dey L, Spranger S, Korenke GC, Schreyer I, Hertzberg C, Neumann TE, Burkart P, Spaich C, Meng M, Holthausen H, Adès L, Seidel J, Mangold E, Buyse G, Meinecke P, Schara U, Zeschnigk C, Muller D, Helland G, Schulze B, Wright ML, Kortge-Jung S, Hehr A, Bogdahn U, Schuierer G, Kohlhase J, Aigner L, Wolff G, Hehr U, Winkler J
Neurology 2007 Jul 31;69(5):442-7. doi: 10.1212/01.wnl.0000266629.98503.d0. PMID: 17664403

Clinical prediction guides

Monoallelic and biallelic mutations in RELN underlie a graded series of neurodevelopmental disorders.
Di Donato N, Guerrini R, Billington CJ, Barkovich AJ, Dinkel P, Freri E, Heide M, Gershon ES, Gertler TS, Hopkin RJ, Jacob S, Keedy SK, Kooshavar D, Lockhart PJ, Lohmann DR, Mahmoud IG, Parrini E, Schrock E, Severi G, Timms AE, Webster RI, Willis MJH, Zaki MS, Gleeson JG, Leventer RJ, Dobyns WB
Brain 2022 Sep 14;145(9):3274-3287. doi: 10.1093/brain/awac164. PMID: 35769015Free PMC Article
Tubulin genes and malformations of cortical development.
Romaniello R, Arrigoni F, Fry AE, Bassi MT, Rees MI, Borgatti R, Pilz DT, Cushion TD
Eur J Med Genet 2018 Dec;61(12):744-754. Epub 2018 Jul 17 doi: 10.1016/j.ejmg.2018.07.012. PMID: 30016746
Congenital Zika Virus Infection: Beyond Neonatal Microcephaly.
Melo AS, Aguiar RS, Amorim MM, Arruda MB, Melo FO, Ribeiro ST, Batista AG, Ferreira T, Dos Santos MP, Sampaio VV, Moura SR, Rabello LP, Gonzaga CE, Malinger G, Ximenes R, de Oliveira-Szejnfeld PS, Tovar-Moll F, Chimelli L, Silveira PP, Delvechio R, Higa L, Campanati L, Nogueira RM, Filippis AM, Szejnfeld J, Voloch CM, Ferreira OC Jr, Brindeiro RM, Tanuri A
JAMA Neurol 2016 Dec 1;73(12):1407-1416. doi: 10.1001/jamaneurol.2016.3720. PMID: 27695855
The wide spectrum of tubulinopathies: what are the key features for the diagnosis?
Bahi-Buisson N, Poirier K, Fourniol F, Saillour Y, Valence S, Lebrun N, Hully M, Bianco CF, Boddaert N, Elie C, Lascelles K, Souville I; LIS-Tubulinopathies Consortium, Beldjord C, Chelly J
Brain 2014 Jun;137(Pt 6):1676-700. doi: 10.1093/brain/awu082. PMID: 24860126
Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing.
Guerrini R, Carrozzo R
Seizure 2002 Apr;11 Suppl A:532-43; quiz 544-7. PMID: 12185771

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