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. 2025 Oct 4.
doi: 10.1002/mdc3.70383. Online ahead of print.

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

Pooja Sharma #  1   2 , Ayush Agarwal #  3 , Tiyasha De  1 , Jupita Handique  1 , Kriti Kashyap  4 , Divyani Garg  3 , Ajay Garg  5 , Shahrumi Reza  1   2 , Akhilesh Kumar Sonakar  3 , Achal K Srivastava  3 , Mohammed Faruq  1   2
Affiliations

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

Pooja Sharma et al. Mov Disord Clin Pract. .

Abstract

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.

Keywords: MFSD8; ataxia; autosomal recessive.

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