Infantile Spasm Syndrome-2, X-linked

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, 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.