Epileptic Encephalopathy due cyclin-dependent kinase type 5 (CDKL5) gene changes: a case report

Case presentation: S.S.A, 2 years old, female, born at term, with no complications during pregnancy, intrapartum, or neonatal period, and no history of neurological diseases in the family. At 2 months and 20 days of age, she presented her first convulsive crises, initially with 3 and 8 crises in successive days, with duration of seconds, in which the patient expressed muscular rigidity in the upper and lower limbs. Due to the progressive increase of seizure episodes, she was evaluated by a neurologist and a diagnostic investigation was initiated. The initial cranial imaging, electroencephalogram, and echocardiogram exams showed no alterations that could justify the crisis. At one year of age, a genetic panel was performed, which showed developmental epileptic encephalopathy 2 due to the CDKL5 gene. Due to the absence of specific treatment, she continues to use phenobarbital, valproic acid, cannabidiol, clonazepam, and oxcarbamazepine. Currently, the child presents, on average, 2 seizures a day even while taking these medications. The patient presents significant neuropsychomotor developmental delay with partial axial tone, absence of speech, and signs of extrapyramidal release in follow-up with a multidisciplinary team.

Discussion: Cyclin-dependent kinase type 5 (CDKL5) deficiency is an X-linked genetic disorder with mutations in the CDKL5 gene, whose patients suffer severe neurodevelopmental disorders, including early onset childhood epileptic encephalopathy, hypotonia, visual impairment, autism spectrum disorders, and intellectual disability. Intractable epilepsy, a widespread symptom associated with CDKL5 deficiency, can occur from a few hours after birth and extend to ~2 years of life, causing distress to children and burden to caregivers. The incidence of CDKL5 deficiency is ~1:40,000 to 60,000 live births, and is more prevalent in females (4:1), since males do not have the normal CDKL5 gene and thus may not survive intrauterine life. The response of patients with traditional antiepileptic medication treatment is unsatisfactory. Thus, to date, the pathogenic mechanisms of CDKL5 deficiency are not fully understood and there are still no effective therapies.

Final comments: Genetic epileptic encephalopathy due to alteration of the CDKL5 gene is a disease that deserves further study to find more effective therapies and improve the quality of life of patients.

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Artikel online veröffentlicht:
18. September 2023