Details of Disease

General Information of Disease (ID: DISBCZL7)

• Disease Name: Lissencephaly spectrum disorders
• Synonyms: macrogyria; pachygyria; Broad gyri of cerebrum; large gyri of cerebrum; lissencephaly (disease); Lissencephaly; lissencephaly spectrum disorders; lissencephaly
• Definition: The term lissencephaly covers a group of rare malformations sharing the common feature of anomalies in the appearance of brain convolutions (characterized by simplification or absence of folding) associated with abnormal organization of the cortical layers as a result of neuronal migration defects during embryogenesis.|Lissencephaly is a spectrum of gyral abnormalities. Lissencephaly, pchygyria and subcortical band heterotopia are known to be caused by the same genes. The distinction between these radiographic terms is not clear cut. The clinical consequences for these radiographic abnormalities is also often overlapping.
• Disease Hierarchy:
  DISQCXZX: Disorder of development or morphogenesis
  DIS2BIP8: Congenital nervous system disorder
  DISD715V: Hereditary neurological disease
  DISBCZL7: Lissencephaly spectrum disorders
• Disease Identifiers:
  MONDO ID: MONDO_0018838
  MESH ID: D054082
  UMLS CUI: C0266463
  MedGen ID: 78604
  HPO ID: HP:0001339
  Orphanet ID: 48471
  SNOMED CT ID: 204036008

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 20 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TUBG1	OT7OU5J6	Definitive	Autosomal dominant	[1]
PAFAH1B1	OT9T2TCJ	Limited	Biomarker	[4]
DISC1	OT43AW4H	Disputed	Genetic Variation	[5]
NDE1	OT2N8Q17	moderate	Genetic Variation	[6]
ADGRG1	OTQBB8NT	Strong	Biomarker	[7]
APC2	OTRH91CX	Strong	Autosomal recessive	[1]
CHCHD2	OTL5PA3Y	Strong	Altered Expression	[8]
CRADD	OT02TZ4S	Strong	Genetic Variation	[9]
CTNNA2	OTJ8G92T	Strong	Biomarker	[2]
DBNL	OTT2OQOV	Strong	Biomarker	[10]
KATNB1	OT7CLZKS	Strong	Genetic Variation	[11]
KIAA0319	OTN42Y77	Strong	Genetic Variation	[12]
KIF2A	OT2WQ6QD	Strong	Genetic Variation	[13]
MACF1	OTVIHD77	Strong	Genetic Variation	[14]
NDEL1	OTAGFML5	Strong	Biomarker	[15]
RELN	OTLKMW1O	Strong	Biomarker	[16]
SMG6	OTRCEJQL	Strong	Genetic Variation	[17]
STIL	OT9799VN	Strong	Genetic Variation	[18]
STXBP1	OTRYA8C3	Strong	Genetic Variation	[19]
DCX	OTISR7K3	Definitive	X-linked	[1]

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
APC2	TTSMK36	Strong	Autosomal recessive	[1]
APC2	TTSMK36	Strong	Biomarker	[2]
DAG1	TT4X7PG	Strong	Biomarker	[3]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay. Am J Hum Genet. 2019 Oct 3;105(4):844-853. doi: 10.1016/j.ajhg.2019.08.013.
• [3] Recent advances in the genetic etiology of brain malformations.Curr Neurol Neurosci Rep. 2013 Aug;13(8):364. doi: 10.1007/s11910-013-0364-1.
• [4] Extraciliary roles of the ciliopathy protein JBTS17 in mitosis and neurogenesis.Ann Neurol. 2019 Jul;86(1):99-115. doi: 10.1002/ana.25491. Epub 2019 May 3.
• [5] Does subtle disturbance of neuronal migration contribute to schizophrenia and other neurodevelopmental disorders? Potential genetic mechanisms with possible treatment implications.Eur Neuropsychopharmacol. 2010 May;20(5):281-7. doi: 10.1016/j.euroneuro.2010.02.005. Epub 2010 Mar 5.
• [6] Novel NDE1 homozygous mutation resulting in microhydranencephaly and not microlyssencephaly. Neurogenetics. 2012 Aug;13(3):189-94. doi: 10.1007/s10048-012-0326-9. Epub 2012 Apr 15.
• [7] GPR56-related bilateral frontoparietal polymicrogyria: further evidence for an overlap with the cobblestone complex.Brain. 2010 Nov;133(11):3194-209. doi: 10.1093/brain/awq259. Epub 2010 Oct 7.
• [8] CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly.Genomics. 2015 Oct;106(4):196-203. doi: 10.1016/j.ygeno.2015.07.001. Epub 2015 Jul 15.
• [9] Phenotypic spectrum associated with a CRADD founder variant underlying frontotemporal predominant pachygyria in the Finnish population.Eur J Hum Genet. 2019 Aug;27(8):1235-1243. doi: 10.1038/s41431-019-0383-8. Epub 2019 Mar 26.
• [10] Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex.J Neurosci. 2019 Jan 23;39(4):678-691. doi: 10.1523/JNEUROSCI.1634-18.2018. Epub 2018 Nov 30.
• [11] Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics.Sci Rep. 2017 Jan 12;7:39902. doi: 10.1038/srep39902.
• [12] Cytoskeleton in action: lissencephaly, a neuronal migration disorder.Wiley Interdiscip Rev Dev Biol. 2013 Mar-Apr;2(2):229-45. doi: 10.1002/wdev.67.
• [13] Recurrent KIF2A mutations are responsible for classic lissencephaly.Neurogenetics. 2017 Apr;18(2):73-79. doi: 10.1007/s10048-016-0499-8. Epub 2016 Oct 17.
• [14] MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance. Am J Hum Genet. 2018 Dec 6;103(6):1009-1021. doi: 10.1016/j.ajhg.2018.10.019. Epub 2018 Nov 21.
• [15] Expression profiles of ndel1a and ndel1b, two orthologs of the NudE-Like gene, in the zebrafish.Gene Expr Patterns. 2007 Jun;7(6):672-9. doi: 10.1016/j.modgep.2007.03.003. Epub 2007 Mar 30.
• [16] The Reeler Mouse: A Translational Model of Human Neurological Conditions, or Simply a Good Tool for Better Understanding Neurodevelopment?.J Clin Med. 2019 Dec 1;8(12):2088. doi: 10.3390/jcm8122088.
• [17] Evidence for association between structural variants in lissencephaly-related genes and executive deficits in schizophrenia or bipolar patients from a Spanish isolate population.Psychiatr Genet. 2008 Dec;18(6):313-7. doi: 10.1097/YPG.0b013e3283118725.
• [18] Genetics and biology of microcephaly and lissencephaly.Semin Pediatr Neurol. 2009 Sep;16(3):120-6. doi: 10.1016/j.spen.2009.07.001.
• [19] Neonatal epilepsies: Clinical management.Semin Fetal Neonatal Med. 2018 Jun;23(3):204-212. doi: 10.1016/j.siny.2018.01.004. Epub 2018 Jan 31.