Adult onset dystonia, chorea or related movement disorder

Gene: XK

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Created: 26 Mar 2025, 2:26 p.m. | Last Modified: 26 Mar 2025, 2:26 p.m.

Panel Version: 4.10

Comment on publications: PMID:39315078 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 26 Mar 2025, 2:26 p.m. | Last Modified: 26 Mar 2025, 2:26 p.m.

Panel Version: 4.9

Numerous variants have been reported in cases of McLeod syndrome (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554).

McLeod syndrome causes a multi-system disorder. The presentation can resemble Huntington Disease. Typically primary manifestations are neurological (e.g. chorea, tics, parkinsonism, dystonia, seizures) and muscular (myopathy, peripheral neuropathy), some patients also exhibited cognitive issues, psychiatric symptoms (psychosis, delusions, depression, obsessive-compulsive features), and emotional lability.

Onset is typically in the 4th decade of life and therefore appropriate for this panel.
Sources: Literature

Created: 26 Mar 2025, 2:15 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
McLeod syndrome, OMIM:300842

Publications

• 8619554
• 21714011
• 11761473
• 17469188
• 23192927
• 37720304
• 34487382
• 35977449
• 24098554
• 39315078