CDKL5 deficiency disorder
CDKL5 deficiency disorder (CDD) is a rare genetic disorder caused by pathogenic variants in the gene CDKL5. Signs and symptoms 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. Patients usually present first with seizures within the first months of life, followed by infantile spasms which progress to epileptic seizures that are largely refractory to treatment. Development of gross motor skills, such as sitting, standing, and walking, is severely delayed, along with restricted fine motor skills. About one-third of affected individuals can ambulate with assistance, but most CDD patients rely on wheelchairs. Additional features include repetitive hand movements (stereotypies), such as clapping, hand licking, and hand sucking; tooth grinding (bruxism); disrupted sleep; feeding difficulties; gastrointestinal problems including constipation and gastroesophageal reflux. Some patients show irregular breathing. Cause CDD is caused by pathogenic variants in the gene CDKL5. This gene provides instructions for making a protein (cyclin-dependent kinase-like 5) that is essential for normal brain development and function. The CDKL5 protein is widely expressed in the brain, predominantly in nerve cells (neurons), with roles in cell proliferation, neuronal migration, axonal outgrowth, dendritic morphogenesis, and synapse