Ordering Recommendation

Preferred initial test to confirm the clinical diagnosis of a CDKL5-related disorder in individuals with infantile seizures, X-linked infantile spasm syndrome, MECP2-negative atypical Rett syndrome, autism, or intellectual disability with seizure disorder.

Mnemonic
CDKL5 FGA
Methodology

Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification

Performed

Varies

Reported

28-35 days

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 2 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 1 Week; Refrigerated: 1 Month; Frozen: 6 Months

Reference Interval
Interpretive Data

Background Information for CDKL5-Related Disorders (CDKL5) Sequencing and Deletion/Duplication:
Characteristics:
Vary widely but may include early onset intractable seizures, severe developmental delay, with females often exhibiting features of Rett syndrome. 
Incidence
: Rare; more frequent in females than males.
Inheritance:
X-linked dominant; reported cases are de novo.
Penetrance:
100 percent.
Cause:
Pathogenic variants in CDKL5 gene.
Clinical Sensitivity:
Approximately 17 percent in females with infantile spasms or seizures.
Methodology:
Bidirectional sequencing of the CDKL5 coding region and intron-exon boundaries. Multiplex ligation-dependent probe amplification (MLPA) to detect large CDKL5 coding region deletions/duplications.
Analytical Sensitivity and Specificity of Sequencing and MLPA
: 99 percent.
Limitations
: Diagnostic errors can occur due to rare sequence variations. Regulatory region and deep intronic variants will not be detected. The breakpoints of large deletions/duplications will not be determined. Single exon deletions/duplications may not be detected due to probe location.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
N/A
CPT Codes

81405; 81406

Components
Component Test Code* Component Chart Name LOINC
2004936 CDKL5-Related Disorder Seq,DelDup Spec 31208-2
2004937 CDKL5-Related Disorder Seq,DelDup Interp 48978-1
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Atypical Rett
  • Epileptic Encephalopathy, Early Infantile 2
  • Infantile Spasms/Atypical Rett
  • Rett-Like Syndrome
CDKL5-Related Disorders (CDKL5) Sequencing and Deletion/Duplication