The symptoms of CDD include early infantile onset refractory epilepsy; hypotonia; developmental, intellectual, and motor disabilities, with little or no speech; and cortical visual impairment.
This gene provides instructions for making a protein (cyclin-dependent kinase-like 5) that is essential for normal brain development and function.
[6] For the clinical diagnosis of CDKL5 Deficiency Disorder, minimal diagnostic criteria have been established, including motor and cognitive delays, epilepsy with onset within the first year of life, and the presence of a pathogenic or likely-pathogenic mutation of the CDKL5 gene.
Initial clinical testing for differential diagnosis may include MRI and CSF testing for structural or infectious etiologies; however, CDKL5 is now widely included in DNA sequence-based molecular diagnostic gene panels or infantile epilepsy for more rapid and precise diagnosis.
This drug, a GABA(A) receptor positive modulator, was approved by the US FDA in March 2022 for the treatment of seizures associated with CDD.
Several efforts are underway to develop small molecule therapeutics to better control seizures, as well as provide management of other non-seizure symptoms, in CDD patients.
If successful, these clinical studies may result in better symptomatic treatments that can provide significant benefit to patients and families in the short term.
[27] In the long term, several independent efforts are advancing truly disease-modifying therapeutics, which are directed at the causative CDKL5 mutation itself.
These include publicly announced clinical and pre-clinical programs in AAV-based gene replacement; genome targeting approaches such as base editing; and inactive X chromosome reactivation.
[28][29] Studies of molecular pathway abnormalities in CDD rodent models may suggest additional possible therapies, such as protein substitution.