AUTHOR=Mastrangelo Mario , Galosi Serena , Cesario Serena , Renzi Alessia , Campea Lucilla , Leuzzi Vincenzo 

TITLE=Presenting Patterns of Genetically Determined Developmental Encephalopathies With Epilepsy and Movement Disorders: A Single Tertiary Center Retrospective Cohort Study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.855134

DOI=10.3389/fneur.2022.855134

ISSN=1664-2295

ABSTRACT=Background This paper aimed to evaluate the frequency of observation of genetically determined developmental encephalopathies with epilepsy and movement disorders in a specialistic centre, the distribution of etiologies and presenting clinical hallmarks, and the mean times for the achievement of molecular genetic diagnosis. 
Patients and Methods Retrospective data about clinical phenotypes, etiology, and diagnostic pathways were collected in all the genetically confirmed patients with developmental encephalopathies with epilepsy and movement disorders referring to our Institution between 2010 and 2020. The cohort was divided in two groups according to the predominant movement disorder type: 1) Group A: patients with hyperkinetic movement disorders; 2) Group B: patients with hypokinetic movement disorders. Both groups were analyzed in terms of developmental, epilepsy and movement disorder phenotypes.
Results The cohort included 69 patients (Group A=53; Group B=16) . The etiological spectrum was heterogeneous with a predominance of Rett and Angelman syndrome in Group A and neurodegenerative disorders in Group B. 
A moderate/severe intellectual disability was assessed in 58/69 patients (mean age at the first signs of developmental impairment=1,87± 1,72 years). Group A included patients with an earlier onset of epileptic seizures (2,63±3,15 versus 4,45±5,55 years of group B) and a predominant generalized motor semiology of seizures at onset. Focal seizures were the main initial epileptic manifestations in Group B. Seizures were noticed earlier than movement disorders in Group A while the opposite occurred in Group B. 
The higher increase of molecular genetic diagnosis was obtained in the last five years. Mean diagnostic delay was longer in Group B than in Group A (12,26±13,32 versus 5.66 ± 6.41 years). Chorea as initial movement disorder was associated with a significantly longer diagnostic delay and a higher age at etiological diagnosis.
Conclusions This study suggested: a) a higher frequency of genetic defects involving neurotransmission, neuronal excitability, or neural development in patients with hyperkinetic movement disorders; b) a higher frequency of neurodegenerative courses and a longer diagnostic delay in patients with hypokinetic movement disorders.