Objective: Disorders of intracellular trafficking may present with different neurological features such as pediatric movement disorders.

Background: A 15-year-old boy presented with a three-year history of jerky movements. These movements occurred in different body parts and relieved during sleep. He was otherwise healthy. His parents were consanguineous. There was no family history of a similar disorder.

Method: His video recordings of the jerky movements were interpreted as paroxysmal attacks of dystonia myoclonus. Neurological exam was normal between attacks.

Results: Whole exome sequencing revealed a frameshift variant (c.12_15del) in VPS11 gene, later confirmed with Sanger sequencing. Parents and siblings were heterozygous carriers and all were healthy.

Conclusion: Disorders of autophagy-lysosomal pathway result in multisystem phenotypes, often presenting with neurological symptoms. The HOPS (homotypic fusion and protein sorting) complex takes part in the fusion of late endosomes and autophagosomes with lysosomes and disruptions to this complex result in inherited dystonias. Mutations in the VPS11 gene encoding a protein for the HOPS complex, were previously reported in neurological disorders. VPS11 mutations were described in hypomyelinating leukodystrophy 12 (HLD12), featuring appendicular spasticity, truncal hypotonia, opisthotonic posturing, and seizures. An adult case with generalised dystonia due to VPS11 mutation was recently reported. Our patient with generalized dystonia and myoclonus is the first pediatric case to our knowledge with a VPS11 gene variant.

References: Monfrini E, Zech M, Steel D, Kurian MA, Winkelmann J, Di Fonzo A. HOPS-associated neurological disorders (HOPSANDs): linking endolysosomal dysfunction to the pathogenesis of dystonia. Brain. 2021 Oct 22;144(9):2610-2615. doi: 10.1093/brain/awab161. PMID: 33871597.

Monfrini E, Cogiamanian F, Salani S, Straniero L, Fagiolari G, Garbellini M, Carsana E, Borellini L, Biella F, Moggio M, Bresolin N, Corti S, Duga S, Comi GP, Aureli M, Di Fonzo A. A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia. Ann Neurol. 2021 Apr;89(4):834-839. doi: 10.1002/ana.26021. Epub 2021 Feb 2. PMID: 33452836; PMCID: PMC8048445.

Yıldız Y, Koşukcu C, Aygün D, Akçaboy M, Öztek Çelebi FZ, Taşcı Yıldız Y, Şahin G, Aytekin C, Yüksel D, Lay İ, Özgül RK, Dursun A. Homozygous missense VPS16 variant is associated with a novel disease, resembling mucopolysaccharidosis-plus syndrome in two siblings. Clin Genet. 2021 Sep;100(3):308-317. doi: 10.1111/cge.14002. Epub 2021 Jun 4. PMID: 34013567.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/vps11-associated-movement-disorder-in-a-pediatric-case/