Details of Disease

General Information of Disease (ID: DISU3ZRI)

• Disease Name: Periventricular nodular heterotopia
• Synonyms: periventricular heterotopia; periventricular nodular heterotopia
• Definition: Periventricular nodular heterotopia (PNH) is a brain malformation, due to abnormal neuronal migration, in which a subset of neurons fails to migrate into the developing cerebral cortex and remains as nodules that line the ventricular surface. Classical PNH is a rare X-linked dominant disorder far more frequent in females who present normal intelligence to borderline intellectual deficit, epilepsy of variable severity and extra-central nervous system signs, especially cardiovascular defects or coagulopathy. The disorder is generally associated with prenatal lethality in males.
• Disease Hierarchy:
  DIS2BIP8: Congenital nervous system disorder
  DISD715V: Hereditary neurological disease
  DIS3P2NS: Nodular neuronal heterotopia
  DISU3ZRI: Periventricular nodular heterotopia
• Disease Identifiers:
  MONDO ID: MONDO_0020341
  MESH ID: D054091
  UMLS CUI: C1868720
  MedGen ID: 358387
  HPO ID: HP:0032388
  Orphanet ID: 98892
  SNOMED CT ID: 816068000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ARF1	TT70KXY	Supportive	Autosomal dominant	[1]
ARF1	TT70KXY	moderate	GermlineCausalMutation	[1]
FLNA	TTSTRZY	Definitive	X-linked	[2]

This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DCHS1	OTW3GX62	Limited	Genetic Variation	[3]
FAT4	OT7QONNV	Limited	Genetic Variation	[3]
FMR1	OTWEV0T5	Limited	Genetic Variation	[4]
ARF1	OT5C4C3L	Supportive	Autosomal dominant	[1]
ARFGEF2	OTM3CQZT	Supportive	Autosomal dominant	[5]
ERMARD	OTRKAQ2L	Supportive	Autosomal dominant	[6]
MAP1B	OTVXW089	Supportive	Autosomal dominant	[7]
NEDD4L	OT1B19RU	Supportive	Autosomal dominant	[8]
TMTC3	OTMTTDYG	Supportive	Autosomal dominant	[9]
ARX	OTBGYH25	Strong	Genetic Variation	[10]
DCX	OTISR7K3	Strong	Genetic Variation	[11]
FAM20C	OTW5YZ7X	Strong	Biomarker	[12]
GNAI2	OTTLGRGH	Strong	Genetic Variation	[13]
HESX1	OT5E2Z4G	Strong	Genetic Variation	[14]
INTS8	OT3SRRLM	Strong	Biomarker	[15]
KIAA0319L	OTZ5X6IM	Strong	Altered Expression	[16]
LLGL1	OTAIQSXZ	Strong	Biomarker	[17]
MOB2	OTMBE0NS	Strong	Genetic Variation	[18]
PAFAH1B1	OT9T2TCJ	Strong	Genetic Variation	[11]
PHF10	OTWDR4EX	Strong	Biomarker	[6]
PLEKHG6	OTZWA27A	Strong	Biomarker	[19]
FLNA	OTYZ9JXM	Definitive	X-linked	[2]

References

• [1] Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation. NPJ Genom Med. 2016;1:16036-. doi: 10.1038/npjgenmed.2016.36. Epub 2016 Oct 5.
• [2] 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.
• [3] Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia.Nat Med. 2019 Apr;25(4):561-568. doi: 10.1038/s41591-019-0371-0. Epub 2019 Mar 11.
• [4] Periventricular heterotopia in fragile X syndrome.Neurology. 2006 Aug 22;67(4):713-5. doi: 10.1212/01.wnl.0000230223.51595.99.
• [5] Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Nat Genet. 2004 Jan;36(1):69-76. doi: 10.1038/ng1276. Epub 2003 Nov 30.
• [6] Periventricular heterotopia in 6q terminal deletion syndrome: role of the C6orf70 gene. Brain. 2013 Nov;136(Pt 11):3378-94. doi: 10.1093/brain/awt249. Epub 2013 Sep 20.
• [7] De novo and inherited private variants in MAP1B in periventricular nodular heterotopia. PLoS Genet. 2018 May 8;14(5):e1007281. doi: 10.1371/journal.pgen.1007281. eCollection 2018 May.
• [8] Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia. Nat Genet. 2016 Nov;48(11):1349-1358. doi: 10.1038/ng.3676. Epub 2016 Oct 3.
• [9] Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy. Hum Mol Genet. 2017 Nov 1;26(21):4278-4289. doi: 10.1093/hmg/ddx316.
• [10] Asymmetric polymicrogyria and periventricular nodular heterotopia due to mutation in ARX.Am J Med Genet A. 2012 Jun;158A(6):1472-6. doi: 10.1002/ajmg.a.35365. Epub 2012 May 14.
• [11] Somatic mutations in cerebral cortical malformations.N Engl J Med. 2014 Aug 21;371(8):733-43. doi: 10.1056/NEJMoa1314432.
• [12] Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS System: Efficacy and description of chronic electrophysiological recordings.Clin Neurophysiol. 2019 Aug;130(8):1196-1207. doi: 10.1016/j.clinph.2019.04.706. Epub 2019 May 9.
• [13] Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability.J Neurochem. 2017 Jan;140(1):82-95. doi: 10.1111/jnc.13878. Epub 2016 Nov 29.
• [14] Ectopic posterior pituitary lobe and periventricular heterotopia: cerebral malformations with the same underlying mechanism?.AJNR Am J Neuroradiol. 2002 Oct;23(9):1475-81.
• [15] Human mutations in integrator complex subunits link transcriptome integrity to brain development. PLoS Genet. 2017 May 25;13(5):e1006809. doi: 10.1371/journal.pgen.1006809. eCollection 2017 May.
• [16] Embryonic disruption of the candidate dyslexia susceptibility gene homolog Kiaa0319-like results in neuronal migration disorders.Neuroscience. 2013 Sep 17;248:585-93. doi: 10.1016/j.neuroscience.2013.06.056. Epub 2013 Jul 3.
• [17] Llgl1 Connects Cell Polarity with Cell-Cell Adhesion in Embryonic Neural Stem Cells.Dev Cell. 2017 Jun 5;41(5):481-495.e5. doi: 10.1016/j.devcel.2017.05.002. Epub 2017 May 25.
• [18] Mob2 Insufficiency Disrupts Neuronal Migration in the Developing Cortex.Front Cell Neurosci. 2018 Mar 12;12:57. doi: 10.3389/fncel.2018.00057. eCollection 2018.
• [19] A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration.Cell Rep. 2018 Dec 4;25(10):2729-2741.e6. doi: 10.1016/j.celrep.2018.11.029.