A Case Series of Stress-Induced Childhood-Onset Neurodegeneration With Variable Ataxia and Seizures (condsias) Caused By Adprhl2 Gene Mutation

Objectives: Biallelic Mutations in ADPRHL2 gene lead to stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS, MIM 618170). Disease onset is in the first decade. Main clinical symptoms are developmental delay, intellectual impairment, gait abnormalities, ataxia, neuropathy, seizures, hearing loss in association with periods of stress, such as febrile illnesses, infections. Here we report clinical and genetic features of nine patient from eight unrelated consanguineous families. Methods: Clinical and genetic data of nine patients were evaluated. Results: One homozygous novel variant were identified, while others were known. Six of the patients were female. Disease onset were between the ages of eight months and 4 years. First symptom was gait disturbance in three patients, speech disturbance in two patients, seizures in two patients, and neck dystonia in two patients. Facial myokymia was observed in seven patients during the follow-up, and tracheostomy was required in six of them in the following periods. EEG examination was performed in six patients and all were found to be normal. Axonal polyneuropathy was detected in the EMG examination of seven patients. Eight patients lost their ambulation in the follow-up Conclusion: CONDSIAS is a rare neurodegenerative disorder. Our findings expand clinical and genetic data. Disease should be considered in the presence of stress-induced gait disturbance, neuropathy, neurodegeneration. Facial myokymia may be a good clue.