Dados do Trabalho

Título

Down Syndrome and KCNT1 related epilepsy

Apresentação do caso

A 3-year-old girl with Down Syndrome (DS), congenital hypothyroidism, global developmental delay and hipotonia started having seizures since one month year old. Since then, she has daily seizures and her first status epilepticus happened at two months years old. Her seizure semiology was characterized by focal clonic jerks or tonic posture associated with autonomic symptoms. The EEG shows diffuse encephalopathy, multifocal discharges, and electrographic focal seizures with typical pattern of epilepsy of infancy with migrating focal seizures (EIMFS). One month year old MRI was normal. One year later, the second one, showed marked delayed myelination, bilateral hippocampal volume loss and diffuse cortical atrophy. The molecular genetic testing identified KCNT1 mutation. Currently, she is on 5 antiseizure medications and ketogenic diet.

Discussão

The prevalence of epilepsy in DS varies between 1-13%. Epilepsy in these patients are usually not related to others genetic etiologies. KCNT1 pathogenic variants are rare and known to cause several epilepsies of infancy and in most cases without brain structural changes on MRI. KCNT1 related epilepsy is a challenging entity itself because of its pleiotropic mutation effects that leads to different phenotypes. EIMFS is a rare developmental and epileptic encephalopathy beginning with drug-resistant, focal seizures in the first year of life, with associated severe encephalopathy. KCNT1 mutation is the main genetic known cause of this syndrome. We described the first case of DS with the typical presentation of KCNT1 epilepsy. The severe neurological disability and the presence of the intractable seizures in this patient may be related to the overlapping of both genetic disorders phenotypes

Comentários finais

This case highlights the importance of differential diagnoses of epilepsy etiology in DS. The precise diagnosis of the epilepsy syndrome and their genetic etiology in these patients can promote more adequate treatment and can improve their life expectancy and quality of life, as well as a better perspective of their prognosis.

Área

GENÉTICA EM EPILEPSIA