Research Information System
Neurology International, vol.18, no.4, 2026 (ESCI, Scopus)
Background/Objectives: Severe neurodevelopmental disorders caused by homozygous ASTN1 variants have recently been reported. The aim of this study is to present the expanded phenotype and prognostic findings through a longitudinal follow-up of a patient with a homozygous ASTN1 variant. Methods: We conducted a 15-year clinical evaluation of a girl who initially presented at 10 years of age. The genetic etiology was investigated using exome sequencing. Results: The patient had a profound intellectual disability, severe expressive language delay, and infantile-onset epilepsy. She also had microcephaly, achieved independent walking at age 7 and had speech limited to only two words at admission. A novel homozygous frameshift variant, c.2096del (p.Cys699Serfs*22), in ASTN1 was identified. Over the follow-up period, her postnatal microcephaly became more pronounced, and she experienced a late relapse into generalized tonic–clonic seizures after a decade-long remission. She remains entirely dependent on caregivers for basic self-care at age 25. Conclusions: ASTN1-related phenotype is associated with a severe neurodevelopmental disease, and the late relapse of seizures after prolonged remission highlights the need for lifelong neurological monitoring and multidisciplinary care.