Atypical Rett Syndrome/ X-linked Infantile Spasms (CDKL5 Sequence Analysis)
- Synonyms: RETT SYNDROME VARIANT WITH INFANTILE SPASMS, ISSX2, STK9
- LIS Mnemonic: MBCDKL5SEQ
Collect
Collect whole blood in a purple top (EDTA) tube.
Volume Required
5ML
Minimum Required
3ML
Transport
Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.
Stability
Whole blood can be refrigerated until shipment.
Unacceptable conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Specimen Handling
Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.
Days Performed
Mon - Fri 9:00am to 4:00pm
Reported
4-6 weeks
CPT
81406
Disease Information
Clinical Features:
X-linked cyclin-dependent kinase-like 5-associated encephalopathy (CDKL5) is an X-linked disorder with a phenotype overlapping that of Rett syndrome and X-linked infantile spasms (ISSX). Rett syndrome is caused by mutations in the MeCP2 gene, and clinical symptoms include loss of speech and purposeful hand use, microcephaly, seizures, ataxia, and stereotypic hand movements. Similar to MECP2, CDKL5 mutations are mostly found in females and rarely in males. The spectrum of phenotypes corresponding to CDKL5-related encephalopathy includes the following: patients with some of the diagnostic criteria of Rett early onset seizure variant, patients characterized by severe encephalopathy with refractory seizures, patients with X-linked infantile spasms and finally, patients with autistic features.
Molecular Genetics:
CDKL5 is located on Xp22 and contains 20 coding exons. CDKL5 is involved in mediating the phosphorylation of the methyl-CpG-binding protein 2 (MECP2). More than 30 pathogenic mutations including missense, nonsense, splice-site and small insertion and deletion mutations have been identified throughout the CDKL5 gene. Germline mosaicism and de novo mutations have been reported.
Test Methods:
We offer DNA sequence analysis of the entire coding region (exons 2-21) including splice junctions. PCR amplification and sequencing is performed on all coding exons. The patient’s gene sequence is then compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Large deletions, mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay.
Detection Rate:
Point mutations are present in about 10-17% of the girls affected with early onset seizures or a Rett like phenotype. CDKL5 mutations in males are less common in the literature although studies have shown that CDKL5 mutations are present in boys presenting with severe early-onset encephalopathy and intractable epilepsy. The analytical sensitivity of this assay is 99%.
Related Tests:
Atypical Rett syndrome/Infantile Spasms Panel: ARX/MECP2/CDKL5 Sequencing + MECP2 Deletion/Duplication Analysis
Rett syndrome: MECP2 Gene Sequencing
Rett syndrome: MECP2 Gene Deletion/Duplication Analysis
Infantile Spasms: ARX Sequencing
Congenital Variant of Rett syndrome: FOXG1 Sequencing
Known mutation analysis is available to family members for mutations previously identified by sequence analysis.
Prenatal testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory director to discuss appropriate testing prior to collecting a prenatal specimen.
Results:
Test results with interpretation will be mailed and/or faxed to the referring physician or laboratory following completion of the test. Additional reports will be provided as requested.
Utility:
The clinical utility of such testing is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at - risk family members.
Remarks
Whole blood in EDTA purple top tubes is the preferred sample. High molecular weight genomic DNA, cheek epithelial cells, or other samples containing DNA may be acceptable. Contact the laboratory for specific instructions regarding such samples before sending the sample.
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