Affiliations: Division of Epilepsy, Department of Neurology, Children’s Hospital Boston, Boston, MA, USA | Department of Neurology, Harvard Medical School, Boston, MA, USA
Note:  Corresponding author: Annapurna Poduri, Epilepsy Genetics Program, Division of Epilepsy and Neurophysiology, Department of Neurology, 300 Longwood Ave., Boston, MA 02115, USA. Tel.: +1 617 355 8656; Fax: +1 617 730 0463; E-mail: email@example.com.
Abstract: CDKL5 mutations have been recognized as a cause of early onset epileptic encephalopathy, particularly in females with atypical Rett syndrome. After presenting a case with a CDKL5 mutation, we review the literature on reported cases of CDKL5 mutations and summarize the clinical phenotype including epilepsy, electrophysiology, neuroimaging, physical examination, development, and other clinical features. The typical phenotype associated with a CDKL5 mutation is early onset epilepsy in a girl with severe developmental delay and hypotonia. Other features frequently include microcephaly, growth retardation, and Rett-like features (deceleration of head growth, hand stereotypies, autistic features, breathing dysfunction, and sleep disturbances). Neuroimaging may be normal or show atrophy or T2 signal change in the posterior, temporal, or periventricular white matter. Epilepsy commonly includes infantile spasms and seizures with multiple distinct phases within one seizure epoch. Male cases with a similar phenotype are also described. CDKL5 gene testing should be considered in patients of both genders with unexplained early onset epilepsy, developmental delay/intellectual disability, and hypotonia with or without microcephaly, growth retardation, poor visual fixation, or Rett-like features. Making the genetic diagnosis of a CDKL5 mutation in a child with early onset epileptic encephalopathy provides a precise diagnosis that allows for counseling about prognosis and genetic counseling.
Keywords: CDKL5, early onset epilepsy, epileptic encephalopathy, Rett syndrome