West Syndrome

X-linked early infantile epileptic encephalopathy (EIEE2) is characterized by intractable early-onset tonic seizures or spasms. This disorder is genetically heterogeneous, with up to a fifth of cases resulting from mutations in the CDKL5 gene. The majority of patients with CDKL5 mutations are female. Females with CDKL5 mutations typically present with drug-resistant seizures that begin before 6 months of age, and more than 90% show a phenotype before the end of the first year. Up to 70% of affected females develop infantile spasms (IS), often in conjunction with hypsarrythmia, and in some cases, they are diagnosed with West syndrome.4,7,11 Some females also present with autism, hypotonia, and developmental delay.1-5 Some of these patients have features reminiscent of Rett syndrome, including breathing dysfunction, deceleration of head growth and stereotypic hand movements. However, unlike those with Rett syndrome, patients with CDKL5 mutations do not demonstrate developmental regression with loss of language and motor skills after normal development in the first year of life. An Angelman syndrome-like phenotype has also been observed in some female patients.1,2,11,12 Male individuals with a CDKL5 mutation typically also develop epileptic encephalopathy characterized by severe intractable seizures and intellectual disability in the absence of other signs.

Tests Available

Forms and Documents

Test Details

CDKL5
  • Confirmation of clinical diagnosis
  • Differentiation of CDKL5-related atypical Rett syndrome from classic Rett syndrome (in patients who tested negative for a MECP2 mutation)
  • Differentiation between de novo and familial cases
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

3051
6-7 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81406x1
No
Yes
  • 315.3 Developmental speech or language disorder
  • 45.6 Infantile spasms
  • 318 Other specified mental retardation
  • 299 Pervasive developmental disorders
  • 299 Pervasive developmental disorders
  • 315.9 Unspecified delay in development, Developmental disorder NOS, Learning disorder NOS
* For price inquiries please email zebras@genedx.com

References

  1. Van Esch H et al., Am J Med Genet A. 2007;143(4):364-9
  2. Kalscheuer VM et al., Am J Hum Genet. 2003;72(6):1401-11
  3. Mari F et al., Hum Mol Genet. 2005;14(14):1935-46
  4. Evans JC et al., Eur J Hum Genet. 2005;13(10):1113-20
  5. Tao J et al., Am. J. Hum. Genet. 75: 1149-1154, 2004
  6. Weaving LS et al., Am J Hum Genet 2004; 75:1079-1093
  7. Rosas-Vargas H et al., J Med Genet 2008; 45: 172-178
  8. Archer HL et al., J Med Genet 2006; 43:729-734

Forms and Documents

Test Details

ADSL, ALDH7A1, ALG13, ARHGEF9, ARX, ATP1A2, ATP6AP2, CACNA1A, CDKL5, CHD2, CHRNA2, CHRNA4, CHRNA7, CHRNB2, CLN3, CLN5, CLN6, CLN8, CNTNAP2, CSTB, CTSD, DNAJC5, DNM1, DYRK1A, EEF1A2, EPM2A, FOLR1, FOXG1, GABRA1, GABRB2, GABRB3, GABRG2, GAMT, GATM, GOSR2, GRIN1, GRIN2A, GRIN2B, IQSEC2, KANSL1, KCNB1, KCNJ10, KCNQ2, KCNQ3, KCNT1, KCTD7, LGI1, MAGI2, MBD5, MECP2, MEF2C, MFSD8, NHLRC1, NR2F1, NRXN1, PCDH19, PIGA, PIGO, PIGV, PNKP, PNPO, POLG, PPT1, PRICKLE1, PRRT2, QARS, SCARB2, SCN1A, SCN1B, SCN2A, SCN8A, SLC13A5, SLC25A22, SLC2A1, SLC6A8, SLC9A6, SPTAN1, STXBP1, TBC1D24, TCF4, TPP1 (CLN2), TSC1, TSC2, UBE3A, WDR45, WWOX, ZEB2
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with epilepsy
  • Testing of at-risk relatives for specific known mutation(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

523
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x2, 81406x4, 81407x2
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Bennett S. Pharmacogenomics (2004) 5:433-8.
  2. Andrade DM. Genetic basis in epilepsies caused by malformations of cortical development and in those with structurally normal brains. Hum Genet (2009) 126:173-193.
  3. Macdonald et al. Mutations in GABA receptor subunits associated with genetic epilepsies. J Physiol (2010) 588:1861-1869.
  4. Ottman et al. Genetic testing in the epilepsies – Report of the ILAE Genetics Commission. Epilepsia (2010) 51:655-670.
  5. Weber et al., Genetic mechanisms in idiopathic epilepsy Dev Med Child Neurol (2008) 50:648-654.
  6. Nicita et al., The genetics of monogenic idiopathic epilepsies and epileptic encephalopathy Seizure: Eur J Epilepsy (2011) doi:10.1016/j.seizure.2011.08.007
  7. Deprez et al. Genetics of epilepsy syndromes starting in the first year of life. Neurology (2009) 72:273-281.
  8. Berg et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commision on Classification and Terminology, 2005- 2009. Epilepsia (2010) 51: 676-685.
  9. Ramachandran et al. The autosomal recessively inherited progressive myoclonus epilepsies and their genes Epilepsia (2009) 50:29-36.
  10. Steinlein et al. Genetic mechanisms that underlie epilepsy. Nat Rev Neurosci (2004) 5:401-408.
  11. Pal et al. Genetic evaluation and counseling for epilepsy. Nat Rev Neurol (2010) 6:445-453
  12. Pellock, JM. Understanding co-morbidities affecting children with epilepsy. Neurol (2004) 62:S17-S23.
  13. Pong et al. Developments in molecular genetic diagnostics: An update for the pediatric epilepsy specialist Pediatr Neurol (2011) 44:317-327

Forms and Documents

Test Details

ADSL, ALDH7A1, ALG13, ARHGEF9, ARX, ATP6AP2, CACNA1A, CDKL5, CHD2, CHRNA7, CLN3, CLN5, CLN6, CLN8, CNTNAP2, CTSD, DNM1, DYRK1A, EEF1A2, FOLR1, FOXG1, GABRA1, GABRB2, GABRB3, GABRG2, GAMT, GATM, GRIN1, GRIN2A, GRIN2B, IQSEC2, KANSL1, KCNB1, KCNJ10, KCNQ2, KCNQ3, KCNT1, KCTD7, MAGI2, MBD5, MECP2, MEF2C, MFSD8, NR2F1, NRXN1, PCDH19, PIGA, PIGO, PIGV, PNKP, PNPO, POLG, PPT1, PRRT2, QARS, SCN1A, SCN1B, SCN2A, SCN8A, SLC13A5, SLC25A22, SLC2A1, SLC6A8, SLC9A6, SPTAN1, STXBP1, TBC1D24, TCF4, TPP1 (CLN2), TSC1, TSC2, UBE3A, WDR45, WWOX, ZEB2
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with epilepsy
  • Testing of at-risk relatives for specific known mutation(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

541
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x2, 81405x1, 81406x3, 81407x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Berg et al. (2010) Epilepsia 51: 676-685.
  2. Pellock, JM (2004) Neurol (2004) 62:S17-S23.
  3. Pong et al., (2011) Pediatr Neurol 44:317-327.
  4. Weber et al., (2008) Dev Med Child Neurol 50:648-654.
  5. Nicita et al., (2011) Seizure: Eur J Epilepsy doi:10.1016/j.seizure.2011.08.007
  6. Ottman et al., (2010) Epilepsia 51:655-670.
  7. Pal et al., (2010) Nat Rev Neurol 6:445-453
  8. Deprez et al., (2009) Neurol 72:273-281.
  9. Macdonald et al., (2010) J Physiol 588:1861-1869.
  10. Andrade DM (2009) Hum Genet 126:173-193.

Forms and Documents

Test Details

ALDH7A1, ARX, CDKL5, FOLR1, KCNQ2, KCNQ3, KCNT1, MECP2, MEF2C, PCDH19, PNPO, POLG, SCN1A, SCN1B, SCN2A, SCN8A, SLC2A1, SLC6A8, SPTAN1, STXBP1, TSC1, TSC2
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with epilepsy
  • Testing of at-risk relatives for specific known mutation(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

814
2 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x2, 81406x3, 81407x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Ottman et al., (2010) Epilepsia 51:655-670.
  2. Pong et al., (2011) Pediatr Neurol 44:317-327.
  3. Nicita et al., (2011) Seizure: Eur J Epilepsy doi:10.1016/j.seizure.2011.08.007
  4. Zucca et al., (2008) Arch Neurol 65:489-494.
  5. Harkin et al., (2007) Brain 130:843-852.
  6. Higurashi et al., (2011) Epilepsy Res dio:10.1016/j.eplepsyres.2011.10.014.
  7. Depienne et al., (2009) Plos Genet 5(2):e1000381.
  8. Marini et al., (2010) Neurology 75:646-653.
  9. Hynes et al., (2010) J Med Genet 47:211-216.
  10. Depienne et al., (2010) Hum Mutat 32:E1959-E1975.
  11. Weckhuysen et al., (2012) Ann Neurol 71:15-25.
  12. Carvill et al., (2014) Neurol 82:1245-1253.
  13. Mills et al., (2010) Brain 133:2148-2159.
  14. Nguyen et al., (2006) J Hepatol 45:108-116.
  15. Isohanni et al., (2011) Neurol 76:811-815.
  16. Hunter et al., (2011) Pediatr Neurol 45:311-318.
  17. Kamiya et al., (2004) J Neurosci 24(11):2690-2698.
  18. Ogiwara et al., (2009) Clin Genet 73(13):1046-1053.
  19. Veeramah et al., (2012) Am J Hum Genet 90:502-510.
  20. Saitsu et al., (2010) Am J Hum Genet 886:881-891.
  21. Gospe et al., (2010) Chang Gung Med 33:1-12.
  22. Li et al., (2006) J Hum Genet 52:38-47.
  23. Tao et al., (2004) Am J Hum Genet 75:1149-1154.
  24. Rosas-Vargas et al., (2008) J Med Genet 45:172-178.
  25. Zweier et al., (2010) Hum Mutat 31:722-733.
  26. Grapp et al., (2012) Brain 135:2022-2031.
  27. EpiPM Consortium (2015) Lancet Neurol 14:1219–28.
  28. Wirrell et al., (2015) Epilepsia 56(4):617–625 3

Forms and Documents

Test Details

  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with epilepsy
  • Testing of at-risk relatives for specific known variant(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies
  • Next-Gen Sequencing

Ordering

921
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x4, 81405x3, 81406x2, 81407x1, 81408x2
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Pong et al. (2011) Pediatric Neurology 44 (5):317-27 (PMID: 21481738)
  2. Dyment et al. (2014) Clinical Genetics : (PMID: 25046240)
  3. Michaud et al. (2014) Human Molecular Genetics 23 (18):4846-58 (PMID: 24781210)
  4. Veeramah et al. (2013) Epilepsia 54 (7):1270-81 (PMID: 23647072)
  5. Allen et al. (2013) Nature 501 (7466):217-21 (PMID: 23934111)
  6. EuroEPINOMICS-RES et al. American Journal Of Human Genetics 95 (4):360-370 (PMID: 25262651)
  7. Lee et al. (2014) Jama 312 (18):1880-7 (PMID: 25326637)
  8. McKnight D, Retterer K, Juusola J, Brandt T, Richard G, and Suchy S, Genetic Testing Strategies for Patients with Epilepsy and Neurodevelopmental Disorders; (Abstract #562). Presented at the 2015 ACMG Annual Clinical Genetics Meeting, March 27, 2015, Salt

Forms and Documents

Test Details

ADSL, ALDH7A1, ALG13, ARHGEF9, ARID1B, ARX, ATP1A2, ATP6AP2, ATRX, CACNA1A, CASK, CDKL5, CHD2, CHRNA2, CHRNA4, CHRNA7, CHRNB2, CLN3, CLN5, CLN6, CLN8, CNTNAP2, CREBBP, CSTB, CTSD, DNAJC5, DYRK1A, EEF1A2, EHMT1, EPM2A, FOLR1, GABRA1, GABRB2, GABRB3, GABRG2, GAMT, GATM, GOSR2, GRIN1, GRIN2A, GRIN2B, HNRNPU, IQSEC2, KANSL1, KCNB1, KCNJ10, KCNQ2, KCNQ3, KCNT1, KCTD7, LGI1, MAGI2, MBD5, MECP2, MEF2C, MFSD8, NHLRC1, NR2F1, NRXN1, OPHN1, PCDH19, PHF6, PIGA, PIGO, PIGV, PLCB1, PNKP, PNPO, POLG, PPT1, PRICKLE1, PRRT2, QARS, SCARB2, SCN1A, SCN1B, SCN2A, SCN8A, SLC13A5, SLC25A22, SLC2A1, SLC9A6, SMC1A, SPTAN1, STXBP1, SYNGAP1, TBC1D24, TCF4, TPP1 (CLN2), TSC1, TSC2, UBE3A, WDR45, WWOX, ZEB2
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with epilepsy
  • Testing of at-risk relatives for specific known variant(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies
  • Exon Array CGH

Ordering

953
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81304x1, 81403x1, 81405x3, 81406x2
No
Yes
* For price inquiries please email zebras@genedx.com