Details of Disease

Disease Name

Microlissencephaly

Definition

Microlissencephaly describes a heterogenous group of a rare cortical malformations characterized by lissencephaly in combination with severe congenital microcephaly, presenting with spasticity, severe developmental delay, and seizures and with survival varying from days to years.

Disease Hierarchy

DISBCZL7: Lissencephaly spectrum disorders

DISUCKNT: Microlissencephaly

Disease Identifiers

MONDO ID

MONDO_0015204

MESH ID

D008831

UMLS CUI

C1956147

MedGen ID

365439

HPO ID

HP:0045028

Orphanet ID

1083

SNOMED CT ID

1003374009

General Information of Disease (ID: DISUCKNT)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PLK4	TTGPNZQ	Disputed	Biomarker	[1]
DNMT3A	TTJUALD	Strong	Biomarker	[2]
PNKP	TTHR3IE	Strong	Biomarker	[3]
SLC2A1	TT79TKF	Definitive	Biomarker	[4]
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This Disease Is Related to 25 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ORC1	OTHWU8IJ	Disputed	Biomarker	[5]
TCF4	OTB9ASTK	Disputed	Biomarker	[6]
KATNB1	OT7CLZKS	Supportive	Autosomal recessive	[7]
NDE1	OT2N8Q17	Supportive	Autosomal recessive	[8]
FOXG1	OTAW57J4	moderate	Biomarker	[9]
TBCD	OTS4JKNQ	moderate	Biomarker	[10]
ADGRL2	OTCXD2YR	Strong	Genetic Variation	[11]
BUB1B	OT8KME51	Strong	Biomarker	[12]
CASK	OT8EF7ZF	Strong	Biomarker	[13]
CEP63	OTX3TTZH	Strong	Biomarker	[14]
DNM1L	OTXK1Q1G	Strong	Biomarker	[15]
DONSON	OTN5HE0W	Strong	Biomarker	[16]
DYNC1H1	OTD1KRKO	Strong	Biomarker	[17]
ERCC6	OT2QZKSF	Strong	Biomarker	[18]
KIF2A	OT2WQ6QD	Strong	Biomarker	[17]
KIF5C	OT35570Y	Strong	Biomarker	[17]
KIFBP	OT1XADKG	Strong	Biomarker	[19]
MFSD2A	OTVG1VG0	Strong	Biomarker	[20]
PQBP1	OTXCBEAH	Strong	Biomarker	[21]
SIN3A	OTM8OZWV	Strong	Biomarker	[22]
STAMBP	OTOT2OXM	Definitive	Biomarker	[23]
TRAIP	OTMPT9Y2	Definitive	Biomarker	[24]
TSEN2	OT1UWYRI	Definitive	Biomarker	[25]
TSEN34	OTH5FQHP	Definitive	Biomarker	[25]
TSEN54	OT7MR9LY	Definitive	Biomarker	[25]
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⏷ Show the Full List of 25 DOT(s)

References

1	Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet. 2014 Dec;46(12):1283-1292. doi: 10.1038/ng.3122. Epub 2014 Oct 26.
2	Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Nat Genet. 2019 Jan;51(1):96-105. doi: 10.1038/s41588-018-0274-x. Epub 2018 Nov 26.
3	Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nat Genet. 2010 Mar;42(3):245-9. doi: 10.1038/ng.526. Epub 2010 Jan 31.
4	Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome. Hum Mutat. 2000 Sep;16(3):224-31. doi: 10.1002/1098-1004(200009)16:3<224::AID-HUMU5>3.0.CO;2-P.
5	Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. Nat Genet. 2011 Feb 27;43(4):350-5. doi: 10.1038/ng.776.
6	Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients. J Med Genet. 2008 Nov;45(11):738-44. doi: 10.1136/jmg.2008.060129. Epub 2008 Aug 26.
7	Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors. Neuron. 2014 Dec 17;84(6):1226-39. doi: 10.1016/j.neuron.2014.12.014.
8	Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]. Am J Hum Genet. 2011 May 13;88(5):536-47. doi: 10.1016/j.ajhg.2011.04.003. Epub 2011 Apr 28.
9	A 3 Mb deletion in 14q12 causes severe mental retardation, mild facial dysmorphisms and Rett-like features.Am J Med Genet A. 2008 Aug 1;146A(15):1994-8. doi: 10.1002/ajmg.a.32413.
10	Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.Am J Hum Genet. 2016 Oct 6;99(4):950-961. doi: 10.1016/j.ajhg.2016.08.005. Epub 2016 Sep 22.
11	Pontocerebellar hypoplasia with rhombencephalosynapsis and microlissencephaly expands the spectrum of PCH type 1B.Eur J Med Genet. 2020 Apr;63(4):103814. doi: 10.1016/j.ejmg.2019.103814. Epub 2019 Nov 23.
12	Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004 Nov;36(11):1159-61. doi: 10.1038/ng1449. Epub 2004 Oct 10.
13	Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet. 2008 Sep;40(9):1065-7. doi: 10.1038/ng.194.
14	A primary microcephaly protein complex forms a ring around parental centrioles. Nat Genet. 2011 Oct 9;43(11):1147-53. doi: 10.1038/ng.971.
15	A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med. 2007 Apr 26;356(17):1736-41. doi: 10.1056/NEJMoa064436.
16	Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism. Nat Genet. 2017 Apr;49(4):537-549. doi: 10.1038/ng.3790. Epub 2017 Feb 13.
17	Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat Genet. 2013 Jun;45(6):639-47. doi: 10.1038/ng.2613. Epub 2013 Apr 21.
18	Cerebro-oculo-facio-skeletal syndrome: three additional cases with CSB mutations, new diagnostic criteria and an approach to investigation.J Med Genet. 2008 Sep;45(9):564-71. doi: 10.1136/jmg.2007.057141. Epub 2008 Jul 15.
19	Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems. Am J Hum Genet. 2005 Jul;77(1):120-6. doi: 10.1086/431244. Epub 2005 May 9.
20	A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome. Nat Genet. 2015 Jul;47(7):814-7. doi: 10.1038/ng.3313. Epub 2015 May 25.
21	Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene. J Med Genet. 2006 Jun;43(6):e30. doi: 10.1136/jmg.2005.037556.
22	Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity. Nat Genet. 2016 Aug;48(8):877-87. doi: 10.1038/ng.3619. Epub 2016 Jul 11.
23	Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. Nat Genet. 2013 May;45(5):556-62. doi: 10.1038/ng.2602. Epub 2013 Mar 31.
24	TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nat Genet. 2016 Jan;48(1):36-43. doi: 10.1038/ng.3451. Epub 2015 Nov 23.
25	tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nat Genet. 2008 Sep;40(9):1113-8. doi: 10.1038/ng.204.