Features include always present findings: Dystonia, Shrinkage of the cerebellum (cerebellar atrophy), Ataxia, and Nystagmus and others; and common findings: Hypogonadotropic hypogonadism, Ketosis, Delayed ability to sit, and Absent speech and others.

POLR3K function has not been fully characterized.

Leukodystrophy, hypomyelinating, 21 has limited evidence linking it to mutations in the POLR3K gene on chromosome 16.

Genetic testing for POLR3K is available. Testing is considered research-grade for diagnosis.

Phenotype severity distribution: 12 always present features, 11 common features.

No clinical trials have been registered for leukodystrophy, hypomyelinating, 21.

3 publications have been identified in PubMed for leukodystrophy, hypomyelinating, 21. Research spans Case Report / Case Series (67%) and Review / Meta-Analysis (33%).

Recent Publications

• Sachithanandan S (2026). [PMID: 41643178](https://pubmed.ncbi.nlm.nih.gov/41643178/). *Ann Indian Acad Neurol*. [Case Report / Case Series]

• Florio CA (2025). [PMID: 40518520](https://pubmed.ncbi.nlm.nih.gov/40518520/). *Ital J Pediatr*. [Case Report / Case Series]

• Michell-Robinson MA (2025). [PMID: 40684265](https://pubmed.ncbi.nlm.nih.gov/40684265/). *HGG Adv*. [Review / Meta-Analysis]