Early onset dystonia

Gene: XK

Red List (low evidence)

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants have been reported in cases of McLeod syndrome with or without chronic granulomatous disease (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).
After consultation with Helen Brittain (Clinical Fellow, Genomics England) it has been concluded that it is not appropriate for XK to be green on the Early onset dystonia panel, as the phenotype is not evident in childhood, but rather from the 4th decade of life (PMIDs: 11761473;8004674;11032622;11261514;33652783;30128557;8619554), therefore, variants in XK could be predictive of possible future conditions.

Created: 6 Sep 2022, 5:02 p.m. | Last Modified: 6 Sep 2022, 5:02 p.m.

Panel Version: 1.127

Green List (high evidence)

Several publications including those given above regarding this well characterised link between XK gene and McLeod syndrome in many patients. Phenotype is acanthosis, haemolysis and elevated CK. Neurological phenotype (from OMIM) "Onset of neurologic symptoms ranges between 25 and 60 years (mean onset 30-40 years), and penetrance appears to be high. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy"

Testing not currently offered by UK labs but several accredited European laboratories are offering testing.
Sources: Literature

Created: 23 Sep 2019, 11:09 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
McLeod syndrome with or without chronic granulomatous disease OMIM 300842

Publications

• 11761473
• 11761473

Variants in this GENE are reported as part of current diagnostic practice