Mutations in the CDKL5 gene on Xp22 (cyclin dependent kinase-like 5, OMIM #300203; also known as serine threonine kinase 9 (STK9)) are associated with mental retardation and severe neurological symptoms. The CDKL5 associated phenotype may be severe, with early-onset encephalopathy, infantile spasms, severe global developmental delay, and profound intellectual impairment seen in female and male patients. At the mild end of the spectrum are patients with mild mental retardation with autistic features. Many of these clinical features meet the criteria for the early-onset variant of Rett syndrome. 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 CDKL5, MECP2 mutations manifest a wide range of clinical phenotypes in female and rare male patients, with features overlapping with other mental retardation disorders. Rett syndrome variants have been described and include the preserved speech variant (PSV), the congenital variant, the “early seizure variant” (seizure onset before regression), and the “forme fruste” (with a milder, incomplete clinical course and regression between 1 and 3 years). Mutation analysis of the CDKL5 gene should be considered in patients with the neurological phenotypes associated with mutations in this gene. In addition, patients who previously tested negative for comprehensive mutation analysis in the MECP2 gene are candidates for CDKL5 sequence analysis.

Reasons For Referral:

• Molecular diagnosis of patients with clinical features associated with CDKL5 mutation.
• Prenatal testing for known familial mutation.
• Assessment of carriers in high risk family members – known mutation analysis.

Testing Methodology:

Sequencing Analysis: PCR amplification of 21 exons contained in the CDKL5 gene coding region is performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult/Child: Minimum 6-14 cc
Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

4 weeks

CPT Codes and Prices:

Index: 83904X25, 83912, 83909X25, 83898X12, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Weaving LS, et al. (2004) Am. J. Hum. Genet. 75: 1079-1093.
2. Scala E, et al. (2005) J. Med. Genet. 42: 103-107.

Shipping Information

Forms:

 >> Gene Sequencing Requisition
 >> Prenatal Requisition

Test Codes:

Index: 6126
Known Familial Mutation: 6129
Prenatal (Known Familial Mutation Only): 6132

Medical Genetics Laboratories
Baylor College of Medicine · Houston, TX 77030
Phone: 1-800-411-GENE · Fax: 713-798-6584
E-mail: