Early onset dystonia

Gene: CYP27A1

Red List (low evidence)

CYP27A1 (cytochrome P450 family 27 subfamily A member 1)
EnsemblGeneIds (GRCh38): ENSG00000135929
EnsemblGeneIds (GRCh37): ENSG00000135929
OMIM: 606530, Gene2Phenotype
CYP27A1 is in 29 panels

1 review

Philip Dawson (Leadiant Biosciences)

Green List (high evidence)

1. In 2018, Stelten et al published a literature review ‘Movement Disorders in cerebrotendinous xanthomatosis’ in which they presented 55 CTX patients with a movement disorder from 39 articles and 7 patients with Parkinsonism from a cohort of 79 Dutch CTX patients. 1
A movement disorder was the presenting symptom in 18% of cases.
However, they also state that ‘Unusual movement disorders represent a rare clinical feature in CTX, but CTX should be considered in the differential diagnosis of these movement disorders, particularly in case of early onset, and when associated with other neurological features (especially cognitive impairment, pyramidal and cerebellar signs) and/or with systemic features (such as diarrhoea, cataract and tendon xanthomas).’
2. Also in 2018, Wong et al published the results of another literature review which identified 91 publications and 194 cases which was presented along with their own case series of 5 patient. This quote from the results section shows that CTX can cause corticospinal tract abnormalities, ataxia, gait difficulties and parkinsonism. 2
‘Of these 194 CTX patients, 116 (59.8%) had CST abnormalities, 114 (58.8%) had ataxia, 90 (46.4%) had cognitive decline, 74 (38.1%) had gait difficulty, 41 (21.1%) had sensory loss, 37 (19.1%) had seizure, 36 (18.6%) had speech changes, 34 (17.5%) had psychiatric changes, and 19 (9.8%) had parkinsonism;68 (35.0%) had baseline cognitive problems.’
They also calculated Cumulative Incidence Function (CIF) for each CTX symptom which gives an indication of the likelihood of a particular symptom having developed at any given age (best- & worst-case scenario) based on a subset of cases where age of symptom onset was available. The CIF graphs show that whilst Parkinsonism is unlikely to develop before the age of 20, symptoms of ataxia, corticospinal tract abnormalities and gait difficulties can develop in both childhood or adulthood with increasing incidence with age.
1. Stelten et al, Movement disorders in cerebrotendinous Xanthomatosis. Park Rel Dis. 2018; 07.006
2. Wong et al, Natural history of neurological abnormalities in cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2018 Jul;41(4):647-656
Created: 18 Apr 2019, 3:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Cerebrotendinous xanthomatosis, 213700; Dystonia, including childhood & adult onset.


History Filter Activity

17 Oct 2016, Gel status: 1

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

17th Oct 2016: Promoted to version 1. The panel was revised after expert input and internal discussion with the clinical team. Other panels such as hereditary ataxia or dementia may be applied in conjunction with this panel where appropriate for genome analysis.

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

CYP27A1 was added to Early onset dystoniapanel. Sources: Emory Genetics Laboratory