Lissencephaly

Abnormal neuronal migration leads to a variety of brain malformation disorders, including lissencephalies and subcortical band or periventricular nodular heterotopias. Lissencephaly is characterized by a thickened cortex and the absence of folds or gyri (agyria) or the presence of abnormally wide gyri (pachygyria). Lissencephalies can present in different forms and with varying severity, ranging from complete agyria to mixed agyria and pachygyria, or simplified gyri with subcortical band heterotopia (double cortex). Mutations in distinct genes lead to overlapping forms of lissencephaly, including classic smooth lissencephaly, cobblestone lissencephaly, lissencephaly with agenesis of the corpus callosum, and lissencephaly with cerebellar hypoplasia. Subcortical band heterotopia is a mild form of lissencephaly characterized by normal gyri but the presence of an abnormal and often symmetric band of gray matter under the cortex. Lissencephalies uniformly cause developmental delay, epilepsy, and intellectual disability. A group of muscular dystrophy disorders (alpha-dystroglycanopathies) can present as Walker-Warburg syndrome at the severe end of their phenotypic spectrum; this syndrome is characterized by cobblestone lissencephaly, cerebellar abnormalities, eye defects, muscle weakness. Periventricular nodular heterotopia (PVNH) is characterized by the presence of uncalcified nodules of gray matter along the lateral ventricles. X-linked PVNH is a male-lethal disorder and affected females mainly present with focal seizures. A more severe phenotype, including microcephaly, intellectual disability, epilepsy, and quadriparesis, is seen in a rare autosomal recessive form of PVNH.
Polymicrogyria results from abnormal folding of the cerebral cortex, leading to an excessive number of small gyri that can be distinguished from the absence of gyri and thickened cortex in lissencephaly. Polymicrogyria restricted to a specific region of the cortex (focal polymicrogyria) can cause minimal neurologic impairment, but when it is widespread (generalized polymicrogyria) the phenotype is very severe and can consist of intractable epilepsy, intellectual disability, and cerebral palsy.

Tests Available

Forms and Documents

Test Details

ACTB, ACTG1, ADGRG1, AHI1, AKT3, ARFGEF2, ARL13B, ARX, ASPM, ATP6V0A2, B3GALNT2, B3GNT1, B9D1, C5orf42, CASK, CC2D2A, CCND2, CEP290, CEP41, CHMP1A, CLP1, CSPP1, CUL4B, DCX, DYNC1H1, ERMARD, EXOSC3, FAT4, FKRP, FKTN, FLNA, GMPPB, GPSM2, IFT172, INPP5E, ISPD, KIAA1279 (KIF1BP), KIF2A, KIF5C, KIF7, LAMB1, LAMC3, LARGE, MKS1, NDE1, NPHP1, NPHP3, OCLN, OFD1 (CXORF5), OPHN1, PAFAH1B1, POMGNT1, POMGNT2, POMK, POMT1, POMT2, PQBP1, RAB18, RAB3GAP1, RAB3GAP2, RARS2, RELN, RPGRIP1L, RTTN, SEPSECS, SRD5A3, SRPX2, TBC1D20, TCTN1, TCTN2, TCTN3, TMEM138, TMEM216, TMEM231, TMEM237, TMEM5, TMEM67, TSEN2, TSEN34, TSEN54, TTC21B, TUBA1A, TUBA8, TUBB, TUBB2A, TUBB2B, TUBB3, TUBB4A, TUBG1, VLDLR, VPS53, VRK1, WDR62
  • Molecular confirmation of a clinical diagnosis
  • Distinguish between causes and forms of brain malformations
  • Genetic counseling
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

691
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x2, 81406x3, 81407x2, 81408x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Verloes et al. (2015) European Journal Of Human Genetics : Ejhg 23 (3):292-301 (PMID: 25052316).
  2. Piao et al. (2005) Annals Of Neurology 58 (5):680-7 (PMID: 16240336).
  3. Bahi-Buisson et al. (2010) Brain : A Journal Of Neurology 133 (11):3194-209 (PMID: 20929962).
  4. Rivière et al. (2012) Nature Genetics 44 (8):934-40 (PMID: 22729224)
  5. Mirzaa et al. (2014) Nature Genetics 46 (5):510-5 (PMID: 24705253).
  6. Tanyalçin et al. (2013) European Journal Of Paediatric Neurology : Ejpn : Official Journal Of The European Paediatric Neurology Society 17 (6):666-70 (PMID: 23755938).
  7. Bahi-Buisson et al. (2013) Handbook Of Clinical Neurology 111 :653-65 (PMID: 23622213).
  8. Kato et al. (2004) Human Mutation 23 (2):147-59 (PMID: 14722918).
  9. Dobyns, et al. (2010) Epilepsia 51 Suppl 1 :5-9 (PMID: 20331703).
  10. Poirier et al. (2006) Neurogenetics 7 (1):39-46 (PMID: 16235064).
  11. Nawara et al. (2006) American Journal Of Medical Genetics. Part A 140 (7):727-32 (PMID: 16523516).
  12. Verloes A, Drunat S, Gressens P, et al. Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders. 2009 Sep 1 [Updated 2013 Oct 31].
  13. Gardeitchik et al. (2014) European Journal Of Human Genetics : Ejhg 22 (7):888-95 (PMID: 23963297).
  14. Fischer et al. (2012) Human Genetics 131 (11):1761-73 (PMID: 22773132).
  15. Stevens et al. (2013) American Journal Of Human Genetics 92 (3):354-65 (PMID: 23453667).

Forms and Documents

Test Details

ACTB, ACTG1, ADGRG1, AKT3, ARFGEF2, ARX, ASPM, ATP6V0A2, B3GALNT2, B3GNT1, CCND2, CUL4B, DCX, DYNC1H1, ERMARD, FAT4, FKRP, FKTN, FLNA, GMPPB, GPSM2, ISPD, KIAA1279 (KIF1BP), KIF2A, KIF5C, LAMB1, LAMC3, LARGE, NDE1, OCLN, PAFAH1B1, POMGNT1, POMGNT2, POMK, POMT1, POMT2, PQBP1, RAB18, RAB3GAP1, RAB3GAP2, RELN, RTTN, SRD5A3, SRPX2, TBC1D20, TMEM5, TUBA1A, TUBA8, TUBB, TUBB2A, TUBB2B, TUBB3, TUBB4A, TUBG1, VLDLR, WDR62
  • Molecular confirmation of a clinical diagnosis
  • Distinguish between causes and forms of neuronal migration and cortical organization disorders
  • Genetic counseling
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

698
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x2, 81405x2, 81406x4
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Barkovich et al. (2009) Brain : A Journal Of Neurology 132 (Pt 12):3199-230 (PMID: 19933510)
  2. Guerrini et al. (2010) Neurobiology Of Disease 38 (2):154-66 (PMID: 19245832).
  3. Liu et al. (2011) Current Neurology And Neuroscience Reports 11 (2):171-8 (PMID: 21222180)
  4. Aronica et al. (2012) Brain Pathology (Zurich, Switzerland) 22 (3):380-401 (PMID: 22497611).
  5. Cushion et al. (2013) Brain : A Journal Of Neurology 136 (Pt 2):536-48 (PMID: 23361065).
  6. Okumura et al. (2013) Neuropathology 33 (5):553-60 (PMID: 23240987)
  7. Oegema et al. (2012) Am. J. Med. Genet. A 158A (6):1472-6 (PMID: 22585566)
  8. Fry et al. (2014) American Journal Of Medical Genetics. Part C, Seminars In Medical Genetics 166C (2):198-210 (PMID: 24862549)
  9. GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1213/
  10. GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1329/.

Forms and Documents

Test Details

ACTB, ACTG1, ARX, ATP6V0A2, B3GALNT2, B3GNT1, DCX, FKRP, FKTN, GMPPB, ISPD, LAMB1, LARGE, NDE1, PAFAH1B1, POMGNT1, POMGNT2, POMT1, POMT2, RELN, TMEM5, TUBA1A, VLDLR, WDR62
  • Molecular confirmation of a clinical diagnosis
  • Distinguish between causes and forms of neuronal migration and cortical organization disorders
  • Genetic counseling
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

946
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x2, 81405x2, 81406x2, 81407x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Fry et al. (2014) American Journal Of Medical Genetics. Part C, Seminars In Medical Genetics 166C (2):198-210 (PMID: 24862549).
  2. Dyment et al. (2013) Current Neurology And Neuroscience Reports 13 (8):364 (PMID: 23793931)
  3. Devisme et al. (2012) Brain : A Journal Of Neurology 135 (Pt 2):469-82 (PMID: 22323514)
  4. Dobyns WB, Das S. LIS1-Associated Lissencephaly/Subcortical Band Heterotopia. 2009 Mar 3 [Updated 2014 Aug 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Avail
  5. Hehr U, Uyanik G, Aigner L, et al. DCXRelated Disorders. 2007 Oct 19 [Updated 2011 Mar 24]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://ww
  6. Verloes et al. (2015) European Journal Of Human Genetics : Ejhg 23 (3):292-301 (PMID: 25052316).
  7. Kato et al. (2004) Human Mutation 23 (2):147-59 (PMID: 14722918)
  8. Dobyns, et al. (2010) Epilepsia 51 Suppl 1 :5-9 (PMID: 20331703).
  9. Poirier et al. (2006) Neurogenetics 7 (1):39-46 (PMID: 16235064).
  10. Nawara et al. (2006) American Journal Of Medical Genetics. Part A 140 (7):727-32 (PMID: 16523516).

Forms and Documents

Test Details

ACTB, ACTG1, ARX, ATP6V0A2, B3GALNT2, B3GNT1, DCX, FKRP, FKTN, GMPPB, ISPD, LAMB1, LARGE, NDE1, PAFAH1B1, POMGNT1, POMGNT2, POMT1, POMT2, RELN, TMEM5, TUBA1A, VLDLR, WDR62
  • Prenatal imaging findings suggestive of lissencephaly
  • Next-Gen Sequencing
  • Exon Array CGH

Ordering

J793
3 weeks
20 mL Amniotic Fluid
20 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|3 Ug DNA Concentration

Billing

81404x2, 84105x2, 81406x2, 81407x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Fry et al. (2014) American Journal Of Medical Genetics. Part C, Seminars In Medical Genetics 166C (2):198-210 (PMID: 24862549).
  2. Dyment et al. (2013) Current Neurology And Neuroscience Reports 13 (8):364 (PMID: 23793931).
  3. Devisme et al. (2012) Brain : A Journal Of Neurology 135 (Pt 2):469-82 (PMID: 22323514).
  4. Senapati et al. (2012) J Pediatr Neuroradiol 1 (3):171-184 (PMID: 24078783).
  5. Conte et al. (2016) AJNR Am J Neuroradiol 37 (5):946-51 (PMID: 26721771).
  6. Williams et al. (2017) Br J Radiol :20160902 (PMID: 28134568).
  7. Dobyns WB, Das S. LIS1-Associated Lissencephaly/Subcortical Band Heterotopia. 2009 Mar 3 [Updated 2014 Aug 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Avail
  8. Hehr U, Uyanik G, Aigner L, et al. DCX-Related Disorders. 2007 Oct 19 [Updated 2011 Mar 24]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://w