Adult onset hereditary spastic paraplegia
Gene: KDM5CThe 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
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
Childhood onset.Created: 22 Sep 2020, 5:01 a.m. | Last Modified: 22 Sep 2020, 5:01 a.m.
Panel Version: 1.7
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
Variants in this GENE are reported as part of current diagnostic practice
limited evidence. On Sheffield's Hsp panel, see current PA review statusCreated: 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
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.
2 families from literature-progressive spastic paraplegia included in clinical feature. In sheffields HSP panelCreated: 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
Phenotypes for gene: KDM5C were changed from Intellectual disability; developmental delay; epilepsy; progressive spasticity; Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; hypothyroidism to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, OMIM:300534
Tag Q3_21_expert_review was removed from gene: KDM5C. Tag Q3_21_phenotype was removed from gene: KDM5C.
Source Expert Review Amber was added to KDM5C. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Publications for gene: KDM5C were set to 10982473; 26919706; 15586325; 18697827
Tag Q3_21_expert_review tag was added to gene: KDM5C. Tag Q3_21_phenotype tag was added to gene: KDM5C.
Publications for gene: KDM5C were set to 10982473; 26919706; 15586325
Source Yorkshire and North East GLH was added to KDM5C.
Added phenotypes Intellectual disability; developmental delay; epilepsy; progressive spasticity; Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; hypothyroidism for gene: KDM5C Publications for gene KDM5C were changed from to 10982473; 26919706; 15586325
Source South West GLH was added to KDM5C.
Source Expert Review Green was added to KDM5C. Mode of inheritance for gene KDM5C was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Added phenotypes Intellectual disability; developmental delay; epilepsy; progressive spasticity; Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; hypothyroidism for gene: KDM5C Rating Changed from Red List (low evidence) to Green List (high evidence)
Source NHS GMS was added to KDM5C.
gene: KDM5C was added gene: KDM5C was added to Hereditary spastic paraplegia - adult onset. Sources: London North GLH Mode of inheritance for gene: KDM5C was set to