KCTD17 – Myoclonic Dystonia 11

KCTD17 has been implicated in myoclonic dystonia 11, a rare movement disorder that traditionally manifests with myoclonic jerks and dystonia. Recent studies have underscored that variants in KCTD17 can lead to an atypical presentation, including features such as dysphonia, vocal tremor, blepharospasm, and writer’s cramp. This gene‐disease relationship expands the classical paradigm associated with other causative genes like SGCE (PMID:32823241).

Genetic evidence arises from multiple independent investigations. In one case report, a 52‑year‑old man with a positive family history presented with late‑onset symptoms including dysphonia and vocal tremor. Genetic analysis identified a heterozygous missense variant, c.229 C>A (p.Leu77Ile), in KCTD17; this finding, coupled with electrophysiological assessments, supports the gene’s involvement (PMID:32823241).

Additional support comes from a multi‐patient study that identified the KCTD17 c.434 G>A (p.Arg145His) mutation in a dominant British pedigree, where seven subjects were affected. The segregation analysis within this family further reinforces the autosomal dominant inheritance pattern and distinct clinical phenotype compared to SGCE‐associated forms (PMID:25983243).

Experimental data bolster the genetic findings. Functional studies, including those based on patient fibroblasts and CRISPR/Cas9‐mediated knockout models, have revealed disruptions in endoplasmic reticulum‐dependent calcium signaling and highlighted KCTD17’s role within a putamen gene network enriched for dystonia associated molecules. These experimental findings are concordant with the clinical manifestations observed in patients (PMID:38732215).

Integrating genetic and functional data, the evidence supports a strong association between KCTD17 variants and myoclonic dystonia 11. Both the identification of recurrent missense variants and consistent segregation patterns in autosomal dominant families, alongside functional assays demonstrating the underlying pathomechanism, contribute broadly to diagnostic decision‑making, commercial development, and future research publication.

Key take‑home: KCTD17-associated myoclonic dystonia 11 represents a clinically actionable entity, particularly in cases exhibiting late‑onset and predominant laryngeal involvement.

References

• Parkinsonism & Related Disorders • 2020 • KCTD17‑related myoclonus‑dystonia syndrome: clinical and electrophysiological findings of a patient with atypical late onset PMID:32823241
• American Journal of Human Genetics • 2015 • A missense mutation in KCTD17 causes autosomal dominant myoclonus‑dystonia PMID:25983243
• International Journal of Molecular Sciences • 2024 • KCTD Proteins Have Redundant Functions in Controlling Cellular Growth PMID:38732215

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