Longitudinal, multidimensional, observational study of 15 patients with CDKL5 Deficiency Disorder

CDKL5 Deficiency Disorder (CDD) is a rare developmental and epileptic encephalopathy characterized by dominant X-linked inheritance and early infantile onset. To date, more than 300 pathogenic variants of the CDKL5 gene have been reported with different phenotypes. As a rare genetic disease, data on CDD are still limited, making the diagnostic and therapeutic process very challenging. The objective of our study was to provide a comprehensive overview of CDD, including those aspects of the disease for which there is unfortunately still limited knowledge.

The presence of a CDKL5 variant, cognitive impairment/delayed psychomotor development, and onset of epilepsy within the first year of life were screened for the diagnosis. Comprehensive clinical assessment, laboratory and radiological investigations were performed.

Fifteen (n=15) patients were enrolled in the study. In most cases, concordance was found between our data and those already present in the literature. In contrast, some other features, including the development of macrocephaly and the presence of congenital gastrointestinal malformations and spinal cord abnormalities, differ from previous findings.

Our study provides an overview on CDD, including those features for which we still have limited knowledge and, albeit on a limited sample, several insights on this rare condition.