Authors :
Presenting Author: Hsiu-Fen Lee, MD Ph.D – Taichung Veterans General Hospital
Ching-Shiang Chi, M.D. – Physician, Division of Pediatric Neurology, Children's Medical Center, Taichung Veterans General Hospital; Chi-Ren Tsai, Ph.D – Medical Staff, Division of Pediatric Neurology, Children's Medical Center, Taichung Veterans General Hospital; Pei-Yu Wu, M.D. – Physician, Division of Pediatric Neurology, Children's Medical Center, Taichung Veterans General Hospital; Yoa-Lun Yang, M.D. – Physician, Division of Pediatric Neurology, Children's Medical Center, Taichung Veterans General Hospital
Rationale:
TBC1D24-related disorders comprise a continuum of distinct and recognizable phenotypes, with epilepsy being a major clinical manifestation. Recessive mutations in TBC1D24 lead to pleiotropic epilepsies and epilepsy syndromes, in which TBC1D24 developmental and epileptic encephalopathy (DEE) displays a catastrophic clinical course together with neurodevelopmental disorders in pediatric patients. The aim of this study is to describe long-term neurological outcome of TBC1D24 DEE.
Methods:
Individuals who exhibited neonatal/infantile epilepsy and had been diagnosed with biallelic TBC1D24 pathogenic variant-related DEE were enrolled. Electroclinical features, neuroimaging findings, and neurodevelopmental outcomes were analyzed.
Results:
Eight individuals, five males and three females, from six unrelated families, were recruited. The age of seizure onset ranged from fifteen days to seven months. One individual had onychodystrophy and the other seven individuals showed no dysmorphic features and no hearing impairment. All eight individuals showed very prolonged multifocal myoclonus or focal clonic fits, and the interictal EEGs were prone to dissociation with clinical seizures. Five individuals received follow-up brain MRI and four had progressive cerebellar atrophy, in which two exhibited cerebellar ataxia. The most common pathogenic variant was TBC1D24 c.1499C >T (p.A500V) in the TLDc domain and it accounted for twelve of sixteen alleles (75%). All individuals were treatment-resistant epilepsy. Seven individuals had profound psychomotor impairment and one showed normal neurodevelopment. Conclusions:
Advances in diagnostic next generation sequencing have expanded to our understanding of this rare TBC1D24-related DEE. Intrafamilial and interfamilial phenotypic variabilities of cerebellar neurodegeneration on neuroimages and neurodevelopmental outcomes need further investigation.Funding: No