Dados do Trabalho

Título

CDKL5 DEFICIENCY DISORDER: CASE REPORT OF A POSSIBLE NEW PATHOGENIC VARIANT

Apresentação do caso

A previously healthy full term 4 month-old (mo) boy, presented by 1-mo with tonic jerks of the upper limbs and slight behavior arrest. He had no signs of infection and no history of recent vaccination. These jerks became daily, more intense, lateralized and associated with oral automatisms and blinking. They had a very brief duration, mostly 20-30 seconds each. EEG showed bilateral temporo-occipital sharp transients and right temporal slow. Phenobarbital was started with partial seizure control; pyridoxine had no effect. Hence, levetiracetam was initiated. A second EEG by the age of 3 months revealed multifocal epileptiform discharges, as well as seizures characterized by pedaling and swimming movements with parietal origin, mostly on the right hemisphere. By this age, he had predominantly axial hypotonia and lost the ability to fix and follow an object. A whole-exome sequencing test showed a chrX:18.598.499 C>G CDKL5 mutation, known as a variant of uncertain significance (VUS) up to now.

Discussão

CDKL5 Deficiency Disorder (CDD) is a rare genetic disorder caused by a mutation in the cyclin-dependent kinase-like5(CDKL5) gene. It is now considered to be a developmental and epileptic encephalopathy because of the early onset of seizures in association with severe global delay. It’s an important cause of early-onset epilepsia (younger than 3mo) associated with severe hypotonia. Seizures are mostly tonic, infantile spasms and, occasionally, hypermotor-tonic-spasms sequence seizures. Other types of focal as well as generalized seizures may occur. Cerebral visual impairment and dysmorphic features are also reported. It is known that CDD enrolled some clinical variants.

Comentários finais

Our case has the typical clinical presentation of this disease although the mutation found is still classified as VUS. Therefore, there is a possibility that this mutation, never described before, can be also responsible for the CDD. This case highlights the importance of the genetic tests and the description of these phenotypes in DEE in order to promote a better understanding of the CDD spectrum.

Referências (se houver)

Wang, H. T., et al. CDKL5 deficiency in forebrain glutamatergic neurons results in recurrent spontaneous seizures. Epilepsia. 2021;62:517-528
Demarest, T.S., et al. CDKL5 deficiency disorders:Relationship between gentotype,epilepsy,cortical visual impairment, and development. Epilepsia.2019;00:1-10.
Zuberi, S. M.;et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants:Position statement by the ILAE Task Force on Nosology and Definitions.Epilepsia.2022;00:1-49.

Declaração de conflito de interesses de TODOS os autores

Nao há