Rett syndrome

Rett syndrome is a progressive, neuro-developmental disorder that affects approximately 1 in 10,000 females. Classic Rett syndrome is diagnosed based on a defined set of clinical criteria and characterized by apparently normal development in the first 6-18 months, followed by an arrest in development and subsequent regression in language and motor skills. Frequent symptoms include loss of speech and purposeful hand use, stereotypic hand movements, ataxia, microcephaly, and seizures. “Atypical” Rett syndrome can be milder or more severe than typical Rett syndrome and is diagnosed when some but not all clinical criteria for Rett syndrome are present. The milder form may include mental retardation, mild learning disablilities and/or autism. Mutations in the MECP2 gene have been found to cause Rett syndrome and “atypical” Rett syndrome in females. In males, MECP2 mutations are not as common and responsible for a broad spectrum of neurodevelopmental phenotypes, ranging from severe neonatal encephalopathy to a variety of neuropsychiatric features or mild mental retardation. Rarely, males with a progressive neurodevelopmental syndrome, including mental retardation, spasticity, speech and social problems, have been found to have a duplication or triplication of the MECP2 gene. CDKL5 mutations have been associated with X-linked mental retardation and a broad spectrum of neurological symptoms that show broad overlap with atypical Rett syndrome and Angelman syndrome. The majority of patients are females. Most patients have a severe phenotype with early-onset encephalopathy and infantile spasms, global developmental delay and mental retardation, although cases with much milder symptoms have been reported.

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 Brushes

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, CACNA1A, CDKL5, CHD2, CHRNA2, CHRNA4, CHRNA7, CHRNB2, CLN3, CLN5, CLN6, CLN8, CNTNAP2, CSTB, CTSD, DYRK1A, EEF1A2, EPM2A, FOLR1, FOXG1, GABRA1, GABRB2, GABRB3, GABRG2, GAMT, GATM, GOSR2, GRIN1, GRIN2A, IQSEC2, KANSL1, KCNT1, KCTD7, LGI1, MAGI2, MBD5, MECP2, MEF2C, MFSD8, NHLRC1, NRXN1, PCDH19, PNKP, POLG, PPT1, PRICKLE1, SCN1A, SCN1B, SCN2A, SLC2A1, SLC6A8, SLC9A6, TBC1D24, TCF4, TPP1 (CLN2), UBE3A, WDR45, 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

542
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)

Billing

81404x2, 81405x2, 81406x2, 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. Macdonald et al., (2010) J Physiol 588:1861-1869.
  9. Andrade DM (2009) Hum Genet 126:173-193
  10. Ramachandran et al., (2009) Epilepsia 50:29-36
  11. Steinlein et al., (2004) Nat Rev Neurosci 5:401-408.
  12. Bennett S. (2004) Pharmacogenomics 5:433-8.
  13. Falace et al., (2010) Am J Hum Genet 87:365-370.

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)

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)

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

MECP2
  • Confirmation of clinical diagnosis
  • Differentiation between de novo and familial cases
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing
  • Exon Array CGH

Ordering

549
4-6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)

Billing

81302x1, 81304x1
No
Yes
  • 315.3 Developmental speech or language disorder
  • 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. Zeev et al. J Child Neurol 17:20-24, 2002
  2. del Gaudio et al. Gene Med 8:784-792, 2006
  3. Van Esch H. et al. Am J Hum Genet 77,:442-453, 2005
  4. Neul et al. Neurology 70:1313-1321, 2008
  5. Bebbington et al. Neurology 70:868-875, 2008
  6. Debona et al. Eur J Hum Genet 8:325-330, 2000
  7. Hitchins et al. Am J Med Genet A 125:167-172, 2004
  8. Couvert et al. Hum Mol Genet 10:941-946, 2001
  9. Kleefstra et al. Eur J Hum Genet 12:24-28, 2004
  10. Abdul-Rahman et al. Genet Med 8:50-54, 2006
  11. Carney et al. Pediatr Neurol 28:205-211, 2003
  12. Villard. J Med Genet 44:417-423, 2007, Bunyan et al. Genet Test 12:373-376, 2008

Forms and Documents

Test Details

CDKL5, CNTNAP2, FOXG1, MBD5, MECP2, MEF2C, NRXN1, SLC9A6, TCF4, UBE3A, WDR45, 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
  • MLPA
  • Next-Gen Sequencing

Ordering

729
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)

Billing

81404x1, 81405x2, 81406x3
Yes
Yes
  • 315.3 Developmental speech or language disorder
  • 345.9 Epilepsy, unspecified [0-1] Epileptic convulsions, fits, or seizures NOS Recurrent seizures NOS Seizure disorder NOS Excludes: convulsion (convulsive) disorder (780.39) convulsive seizure or fit NOS (780.39) recurrent convulsions (780.39)
  • 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. de Siquiera et al., (2010) J Neurol 257:1612-1619
  2. Shawan et al., (2005) Lancet Neurol 4:239-248.
  3. Jansen and Andermann (Updated December 2007). Progressive Myoclonic Epilepsies, Lafora Type. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http:
  4. Lehesjoki and Kalviainan (Updated June 2009) Unverricht-Lundborg Disease. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.or
  5. Mole and Williams (Updated March 2010). Neuronal Ceroid Lipofuscinosis. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org.
  6. Bennett S. (2004) Pharmacogenomics 5:433-8.
  7. Das et al., (1998) J Clin Invest 102:361-370. 8. Sleat et al., (1999) Am J Hum Genet 64:1511-1523.
  8. Munroe et al., (1997) Am J Hum Genet 61:310-316.
  9. Noskova et al., (2011) Am J Hum Genet 89:241-252.
  10. Velinov et al., (2012) PloS One 7:e29729.
  11. Staropoli et al., (2012) Am J Hum Genet 91:202-208.
  12. Dibbens et al., (2009) Ann Neurol 66:532-536.
  13. Berkovic et al., (2008) Am J Hum Genet 82:673-684.
  14. Corbett et al., (2011) Am J Hum Genet 82:673-684.
  15. Lomax et al., (2013) Brain 136:1146-1154.
  16. Grapp et al., (2012) Brain 135:2022-2031.

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)

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

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)

Billing

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