RESUMO
Background and Objectives: Neurodevelopmental disorder with spastic diplegia and visual defect (NEDSDV) is a recently described rare syndrome caused by loss-of-function variations in CTNNB1 gene which includes developmental delay, intellectual deficiency, visual defects, and other features. Startle disease is not present in the classic clinical description and has been reported in only 2 patients so far. Methods: We report 12 cases of patients with NEDSDV who present an exaggerated startle response including 1 patient observed in our department and 11 patients recruited by addressing a questionnaire to the members of the Facebook group of families of patients with a CTNNB1 pathogenic variant. We performed an EMG analysis of this abnormal startle response in 1 patient and a genotype-phenotype analysis of startle response in NEDSDV. Results: All 12 patients presented exaggerated startle responses to an unexpected stimulus. They provoked falls in 8 patients, causing injuries in 3, and 3 patients were afraid to walk. This startle disorder corresponds to atypic hyperekplexia. No genotype to phenotype correlation has been found to differentiate NEDSDV with or without startle disease. Discussion: Our data allow us to refine the phenotypic spectrum of patients affected by CTNNB1-related NEDSDV, suggesting that exaggerated startle reactions may be part of clinical features. A precise questioning on startle disorders should be performed systematically in these patients because they can lead to potentially traumatic falls, while effective treatments are available and can improve quality of life. CTNNB1 study should be considered in patients with startle disease associated with intellectual deficiency.