CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Molecular Biology

Background:

• Rett syndrome is a severe neurodevelopmental disorder primarily affecting females, often caused by MECP2 gene mutations.
• The Hanefeld variant is characterized by early-onset seizures, typically infantile spasms.
• West syndrome involves infantile spasms, hypsarrhythmia, and intellectual disability, with ARX and CDKL5 genes implicated.

Observation:

• Two female patients presented with Rett syndrome features, including acquired microcephaly and hand stereotypies.
• Both patients exhibited early-onset generalized convulsions and myoclonic fits or spasms.
• MECP2 mutations were excluded, and clinical presentation suggested the Hanefeld variant.

Findings:

• Frameshift deletions in the CDKL5 gene were identified in both patients.
• Specific mutations found were c.163_166delGAAA in exon 5 and c.2635_2636delCT in exon 18.
• No CDKL5 mutations were found in MECP2-negative classic Rett syndrome or preserved speech variant patients.

Implications:

• CDKL5 mutations are identified as a cause of a rare variant of Rett syndrome.
• This finding expands the genetic understanding of Rett syndrome spectrum disorders.
• Early identification of CDKL5 mutations can aid in diagnosing this specific Rett syndrome variant.