Inherited white matter disorders

Gene: CYP27A1

Green List (high evidence)

1. In 2018, an International group of experts published an updated version of a ‘Practical approach to the diagnosis of adult-onset leukodystrophies’ which includes the following quote;
‘After excluding common acquired leukoencephalopathies, the first priority should be to identify patients with an inherited metabolic disorder.’
This includes CTX and goes on to highlight some of the common clinical features to corroborate a suspected diagnosis.
2. In 2004 Verrips et al wrote a chapter in ‘Neurocutaneous Disorders’ on CTX which, noted that the majority of advanced CTX patients have white matter findings on CT and / or MRI often including the cerebellum and pyramidal tract but also including a range of other presentations throughout the brain, brainstem & spinal cord.
In summary, CTX is a metabolic condition with progressive involvement of the white matter correlated with a range of neurological symptoms including leukodystrophies.

References
1. Lynch et al, Practical Approach to the diagnosis of adult onset leukodystrophies: an updated guide for the genomics era. J Neurol Neurosurg Psychiatry (2018) Published Online First: 22 November 2018. doi: 10.1136/jnnp-2018-319481
2. Verrips, A., Cruysberg, J., & Wevers, R. (2004). Cerebrotendinous xanthomatosis. In E. Roach & V. Miller (Eds.), Neurocutaneous Disorders (pp. 248-257). Cambridge: Cambridge University Press. doi:10.1017/CBO9780511545054.032

Created: 18 Apr 2019, 3:03 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebrotendinous xanthomatosis, 213700 Inherited white matter disorders.

Publications

• 30467211
• ISBN 9780511545054

Comment on list classification: Gene rated green and diagnostic-grade by expert reviewer. Multiple cases with different variants reported in OMIM. On the Minimum recommended gene list for broad spectrum genetic testing for single-nucleotide variants associated with leukodystrophies and genetic leukoencephalopathies reported in PMID: 25655951.

Created: 12 Aug 2016, 7:48 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
General Leukodystrophy & Mitochondrial Leukoencephalopathy

Publications

• Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_616

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