Adult onset hereditary spastic paraplegia

Gene: KDM5C

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.

Panel Version: 1.95

I don't know

Review of literature showed that KDM5C is associated with a childhood-onset condition (MIM# 300534). However, the presenting feature is developmental delay and intellectual disability. Some patients develop progressive spasticity, but the age of onset is not clear from some case reports. Several publications describe adult patients but without any indication of when spasticity became evident.

Leaving the rating as Green, but with a recommendation for review at the next GMS panel update to assess whether this gene is appropriate for this adult onset panel (tagged Q3_21_phenotype). Inclusion may be justified to ensure identification of edge cases if relevant.

This gene is already Green on the 'Hereditary spastic paraplegia - childhood onset v.2.18' panel.

Created: 19 Aug 2021, 11:34 a.m. | Last Modified: 19 Aug 2021, 11:34 a.m.

Panel Version: 1.39

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
Mental retardation, X-linked, syndromic, Claes-Jensen type, OMIM:300534

Publications

• 10982473
• 15586325
• 18697827
• 19826449
• 26919706
• 32279304

Red List (low evidence)

Childhood onset.

Created: 22 Sep 2020, 5:01 a.m. | Last Modified: 22 Sep 2020, 5:01 a.m.

Panel Version: 1.7

Green List (high evidence)

Spastic diplegia present in majority of cases. Childhood onset. Additional patient with likely de novo nonsense mutation identified using Sheffield panel.

Created: 10 May 2019, 7:47 a.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)

Publications

• 10982473
• 15586325
• 26919706
• 18697827

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

I don't know

limited evidence. On Sheffield's Hsp panel, see current PA review status

Created: 27 Apr 2019, 4:17 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
Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism

Publications

• 10982473
• 15586325
• 26919706

I don't know

Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.

Created: 21 May 2019, 4:14 p.m.

Review and rating submitted byJames Polke (Neurogenetics Laboratory,Institute of Neurology, London), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 4:50 p.m.

Review and rating from Chris Buxton (North Bristol NHS Trust), submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 27 Apr 2019, 4:30 p.m.

Green List (high evidence)

2 families from literature-progressive spastic paraplegia included in clinical feature. In sheffields HSP panel

Created: 25 Apr 2019, 1:22 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
Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism