Dados do Trabalho

Título

EPILEPTIC ENCEPHALOPATHY DUE CYCLIN-DEPENDENT KINASE TYPE 5 (CDKL5) GENE CHANGES – A CASE REPORT

Apresentação do caso

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.

Discussão

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 approximately 2 years of life, causing distress to children and burden to caregivers.
The incidence of CDKL5 deficiency is about 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.

Comentários finais

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.

Referências (se houver)

Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy.
Mei D, Marini C, Novara F, Bernardina BD, Granata T, Fontana E, Parrini E, Ferrari AR, Murgia A, Zuffardi O, Guerrini R.Epilepsia. 2010 Apr;51(4):647-54. doi: 10.1111/j.1528-1167.2009.02308.x. Epub 2009 Sep 22.PMID: 19780792

Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review.
Olson HE, Demarest ST, Pestana-Knight EM, Swanson LC, Iqbal S, Lal D, Leonard H, Cross JH, Devinsky O, Benke TA.Pediatr Neurol. 2019 Aug;97:18-25. doi: 10.1016/j.pediatrneurol.2019.02.015. Epub 2019 Feb 23.PMID: 30928302

CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature.
Lilles S, Talvik I, Noormets K, Vaher U, Õunap K, Reimand T, Sander V, Ilves P, Talvik T.Neuropediatrics. 2016 Dec;47(6):361-367. doi: 10.1055/s-0036-1586730. Epub 2016 Sep 6.PMID: 27599155

CDKL5 deficiency in forebrain glutamatergic neurons results in recurrent spontaneous seizures.
Wang HT, Zhu ZA, Li YY, Lou SS, Yang G, Feng X, Xu W, Huang ZL, Cheng X, Xiong ZQ.Epilepsia. 2021 Feb;62(2):517-528. doi: 10.1111/epi.16805. Epub 2021 Jan 5.PMID: 33400301

Declaração de conflito de interesses de TODOS os autores

Nenhum dos autores apresenta conflito de interesses.