Angelman syndrome (AS)

Angelman syndrome (AS) is a neurological disorder affecting both development and behavior. Individuals with Angelman syndrome exhibit cognitive delays, seizures, ataxia, absence of speech, and characteristic electroencephalogram (EEG) abnormalities. Developmental delay is commonly seen during the first year of life. Characteristic dysmorphic features in AS include a prominent chin, a small head circumference and a wide mouth with protruding tongue. These features are accompanied by behavioral abnormalities, such as sleep disorders and a happy demeanor with recurrent laughter, smiling and excitability. The presence and severity of these clinical features can vary among affected individuals. Similar to those with AS, individuals with Angelman-like syndrome also have mental retardation, ataxia, severe limitations in language and speech, a happy demeanor with frequent smiling or spontaneous laughter, epilepsy, and microcephaly.The X-linked Angelman-like syndrome is primarily found in males, but carrier females occasionally display a mild phenotype that may include learning disabilities

Tests Available

Forms and Documents

Test Details

  • Confirmation of clinical diagnosis
  • Targeted testing for a known familial deletion, UPD or imprinting error
  • Prenatal diagnosis by targeted array CGH for deletions or UPD only (methylation analysis not available for prenatal)
  • MLPA

Ordering

566
3-4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81331x1
No
Yes
  • 315.3 Developmental speech or language disorder
  • 315.9 Unspecified delay in development, Developmental disorder NOS, Learning disorder NOS
* For price inquiries please email zebras@genedx.com

References

  1. Piard et al., (2011) Am J Med Genet 155:3170-3173.
  2. Beleza-Meireles et al., (2011) Eur J Med Genet 54:348-350.
  3. Boyes L., et al. Eur J Med Genet. (2006) 49(6):472-80.
  4. Hu et al., (2009) HUGO J 3:41-49.
  5. Whibley et al., (2010) Am J Hum Genet 87:173-188.
  6. Schroer R., et al. Am J Med Genet. (2009) 152A:2775-2783.
  7. Russo, S., et al, (2000) Hum Mutan 15(4):387-393.
  8. Clayton-Smith, J., et al (2003) J Med Genet 40(2):87-95.
  9. Fang, P., et al, (1991) Hum Molec Genet 8(1):129-135.
  10. Malzac, P., et al, (1998) Am J Hum Genet 62(6):1353-1360.
  11. Gillfillan G et al., Am. J. Hum. Genet. 82(4): 1003-1010, 2008.
  12. Christianson A et al. Am J. Hum Genet. 36:759-766, 1999.
  13. Williams, C.A. and Dagli A.I. (Updated June 16, 2011). Angelman Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2009. Available at http://www.genetests.org
  14. Lossie, A.C., et al, (2001) J Med Genet 38(12):834-845.
  15. Hitchins, M.P., et al, (2004) Am J Med Genet 125A(2):167-172.
  16. Dagli AI.,et al, (2015) GeneReviews

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)|Buccal Swabs

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)|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

UBE3A
  • Confirmation of clinical diagnosis
  • Targeted testing for a known familial mutation
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing

Ordering

374
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
  • 315.9 Unspecified delay in development, Developmental disorder NOS, Learning disorder NOS
* For price inquiries please email zebras@genedx.com

References

  1. Malzac, P., et al, (1998) Am J Hum Genet 62(6):1353-1360
  2. Gillfillan G et al., Am. J. Hum. Genet. 82(4): 1003- 1010, 2008
  3. Schroer R., et al. Am J Med Genet. (2009) 152A:2775-2783
  4. Boyes L., et al. Eur J Med Genet. (2006) 49(6):472-80
  5. Fichou et al. European Journal of Human Genetics (2009) 17, 1378–1380
  6. Russo, S., et al, (2000) Hum Mutan 15(4):387-393
  7. Clayton-Smith, J., et al (2003) J Med Genet 40(2):87-95
  8. Christianson A et al. Am J. Hum Genet. 36:759-766, 1999
  9. Dagli AI, Mueller J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2015 May 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  10. Hitchins, M.P., et al, (2004) Am J Med Genet 125A(2):167-172
  11. Lossie, A.C., et al, (2001) J Med Genet 38(12):834-845
  12. Fang, P., et al, (1991) Hum Molec Genet 8(1):129-135

Forms and Documents

Test Details

UBE3A
  • Confirmation of clinical diagnosis
  • Targeted testing for a known familial mutation
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing
  • ExonArray CGH

Ordering

546
6-7 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81406x1, 81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Boyes L., et al. Eur J Med Genet. (2006) 49(6):472-80
  2. Fichou et al. European Journal of Human Genetics (2009) 17, 1378–1380
  3. Clayton-Smith, J., et al (2003) J Med Genet 40(2):87-95
  4. Russo, S., et al, (2000) Hum Mutan 15(4):387-393
  5. Fang, P., et al, (1991) Hum Molec Genet 8(1):129-135
  6. Hitchins, M.P., et al, (2004) Am J Med Genet 125A(2):167-172
  7. Lossie, A.C., et al, (2001) J Med Genet 38(12):834-845
  8. Dagli AI, Mueller J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2015 May 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  9. Malzac, P., et al, (1998) Am J Hum Genet 62(6):1353-1360
  10. Gillfillan G et al., Am. J. Hum. Genet. 82(4): 1003- 1010, 2008
  11. Christianson A et al. Am J. Hum Genet. 36:759-766, 1999
  12. Schroer R., et al. Am J Med Genet. (2009) 152A:2775-2783

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)|Buccal Swabs

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

  • 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