Adult onset neurodegenerative disorder

Region: ISCA-37446-Loss

22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss

Green List (high evidence)

Comment on list classification: There is sufficient evidence to support this gene-disease association. Several cases with 22q11.2 deletions and Parkinson's disease with or without other features of DiGeorge syndrome have been reported. This is a very variable condition and most case would probably be picked up via other routes, as highlighted by Lauren Turton. However, sufficient numbers have presented where parkinsonism was the primary reason for referral, including the case in Sheffield and in the published literature (PMID: 24018986; 27017469).

Although there is sufficient evidence for inclusion, all regions were removed from this panel in 2020 'as testing is not achievable using currently available methodology' (see comment on other regions). It would be worth reviewing whether this is still the case and therefore this region has been tagged for GMS expert review.

If it is agreed that regions can now be included, other regions on this panel should also be revisited to determine whether they should be re-added.

Created: 28 Oct 2025, 10:29 a.m. | Last Modified: 28 Oct 2025, 10:29 a.m.

Panel Version: 8.8

I don't know

PMID: 24018986 159 adults diagnosed with 22q11.2DS. Four of 68 subjects (5.9%) aged 35 to 64 years with 22q11.2 deletions had been diagnosed as having PD (standardized morbidity ratio = 91.7; 95% CI, 25.0–234.8). Prevalence 5.9% in this cohort, however many of the individuals in 18-34 age group (n=90).

PMID: 27017469 We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001).

In Sheffield we also have a case with DiGeorge syndrome, that was referred for genetic testing due to parkinsonism as the primary referral reason. The patient also had other clinical features compatible with DiGeorge syndrome.

Added as amber as it is likely these patients will have other features that make them eligible for alternative panels such as R29.
Sources: NHS GMS

Created: 29 May 2025, 9:01 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
DIGEORGE SYNDROME; DGS (OMIM: 188400)

Publications

• 24018986
• 27017469

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