MFSD8‐Related CLN7 Disease with Adult‐Onset Cerebellar Ataxia: A Five‐Patient Case Series

Background Adult‐onset recessive cerebellar ataxias comprise a heterogeneous group of disorders. Objectives To describe a founder MFSD8 variant in adult‐onset cerebellar ataxia. Methods We describe three unrelated Indian patients and one sibling pair ( n = 5; median age 31 years) who exhibited progressive gait ataxia, limb dysmetria, titubation, gaze‐evoked nystagmus, hypermetric saccades, and brisk reflexes without seizures, cognitive decline, visual impairment, or autonomic dysfunction. Brain MRI revealed moderate cerebellar atrophy. Results They were all homozygous for MFSD8 c.935T>C(p.Ile312Thr) presenting with pure cerebellar syndrome in the third decade. This ultra‐rare p.Ile312Thr variant was predicted as deleterious by in silico tools and absent in homozygous state in population databases. Runs of homozygosity indicated a shared ~1.3–12Mbp haplotype with a common ancestor ~620 years ago. Conclusions These findings expand MFSD8 ‐related CLN7 disease to include adult‐onset isolated ataxia and support inclusion of MFSD8 in adult ataxia gene panels, particularly in South Asian populations.