CDKL5 (CDKL5-Related Infantile Spasms and Atypical Rett Syndrome)
CDKL5 genetic mutations can be associated with disorders and phenotypes of various severity. Common symptoms in individuals with a CDKL5 mutation can include: Autism, severe intellectual disability, seizures, hypotonia and stereotypic hand movements.
PrintCDKL5 genetic mutations can be associated with disorders and phenotypes of various severity. Common symptoms in individuals with a CDKL5 mutation can include: Autism, severe intellectual disability, seizures, hypotonia and stereotypic hand movements.
Mutations are X-linked dominant and the majority are de novo.
Testing for CDKL5-Related Infantile Spasms should be considered in those with Atypical Rett Syndrome, MECP2-negative Rett Syndrome, X-Linked Infantile Spasms (ISSX, West syndrome, or the Hanefield variant), complex seizures disorders with mental retardation, X-linked Mental Retardation, and Autism Spectrum Disorder.
This Ambry Test is a full Gene Sequence Analysis of the CDKL5 gene. For additional information about MECP2 and Rett syndrome testing, please refer to the Ambry Test: Rett syndrome.
Mutations in the CDKL5 gene, previously known as STK9,1 can result in a wide variety of symptoms and disorders. Common symptoms in individuals with a CDKL5 mutations can include: autism, infantile seizures and spasms, profound intellectual disability, developmental and motor delay, hypotonia, stereotypical hand gestures, and persistent epilepsy.2 Research shows that CDKL5 has an upstream role in the same molecular pathway as MECP2 (gene associated with Rett syndrome, by mediating its phosphorylation. CDKL5 mutations have been associated with atypical variants of Rett syndrome (RTT) and with X-linked Dominant Infantile Spasm syndrome (ISSX2).3
RTT is a severe and progressive neurologic disorder. Further characterized by staggered development in the first 6-18 months, followed by rapid regression in intelligence, language and motor skills. Additional common findings include progressive regression of voluntary hand movement and autistic features.
Atypical variants of Rett syndrome include Infantile Spasm syndrome, also known as West syndrome or the Hanefeld variant. Due to lack of function of the protein associated with CDKL5, symptoms often include severe infantile spasms, profound global developmental arrest, hypsarrhythmia and severe mental retardation.4
X-linked Infantile Spasm syndrome (ISSX) affects 2 to 5 individuals per 10,000 births. Mutations in the CDKL5 gene can cause mental retardation, seizures and infantile spasms, hypotonia, hand stereotypies in 85% of individuals, and autism in 75% of patients with ISSX. Approximately 17% of patients diagnosed with ISSX have a CDKL5 mutation.7
Males with CDKL5 mutations present with severe encephalopathy and early-onset intractable epilepsy.5
Testing for CDKL5 should be considered in those with atypical Rett syndrome, MECP2-negative Rett syndrome, X-Linked Infantile Spasm syndrome, complex seizures disorders with mental retardation, X-linked mental retardation, and Autism Spectrum Disorder.2, 6 Prenatal diagnosis and carrier testing are also available.
CDKL5 full gene sequence analysis performed by PCR-based double-stranded automated sequencing. Sequencing is performed in the sense and antisense directions for exons 2-21 of the CDKL5 gene. Site specific CDKL5 familial mutation analysis is available for known mutations.
Approximately 17% of patients diagnosed with ISSX have a CDKL5 mutation (clinical sensitivity). Ambry can identify approximately 99% of described mutations (analytic sensitivity).
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Technique | Days |
|---|---|
| CDKL5 Gene Sequence Analysis | 10-21 |
1. Weaving LS, Ellaway CJ, Gecz J, Christodoulou J. Rett syndrome: clinical review and genetic update. J Med Genet. 2005;42:1-7. [PMID: 15635068]
2. Bahi-Buisson N, Nectoux J, et al. Key clinical features to identify girls with CDKL5 mutations. Brain. 2008;131:2647-2661. [PMID: 18790821]
3. Scala, E, Ariani, F.,Mari, F, Caselli R, et al. CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. J. Med. Genet. 2005;42,103–107. [PMID: 15689447]
4. Kalscheuer V, Tao J, Donnelly AJ. Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. Am J Hum Genet. 2003;72:1404-1411. [PMID: 12736870]
5. Elia , Falco M, Ferri R, et al. CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy. Neurology. 2008;71:997-999. [PMID: 18809835]
6. Weaving LS, Christodoulou J, Williamson SL, et al. Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am J Hum Genet. 2004;75(6):1079-93. [PMID: 15492925]
7. Archer, H, Evans, J, Edwards, S, et al. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J. Med. Genet. 2006; 43:729-734. [PMID: 16611748]