Early onset or syndromic epilepsy

Gene: CDK19

Green List (high evidence)

Zarate et al 2021-Eleven unrelated individuals (age range: 9 months to 14 years) with de novo missense variants mapped to the kinase domain of CDK19. It was thought that the disease mechanism could be both loss of function and gain of function.
Two recurrent changes at residues Tyr32 and Gly28 were identified.
One additional case report (PMID:33568421) described a 10-month-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms and a de novo missense variant c.92C>A (p.Thr31Asn) (also in the kinase domain). This brings the total of cases reported in the literature to fifteen.
In the series reported by Zarate et al, epilepsy is seen in 64% of the cases.

Created: 22 Feb 2021, 9:38 a.m. | Last Modified: 22 Feb 2021, 9:38 a.m.

Panel Version: 2.303

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
developmental delay; hypotonia; seizures; autism/autistic traits

Publications

• 33495529
• 33568421
• 32330417

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

I don't know

Chung et al 2020 - 3 unrelated indiviuduals with de novo missense variants in CDK19 - presented with hypotonia, global developmental delay, epileptic encephalopathy and dysmorphic features. Two patients had the Thr196Ala variant and the other Tyr32His - predicted to be likely pathogenic. Fuinctional work suggests dominant loss of function variants.

Created: 27 Jan 2021, 4:59 p.m. | Last Modified: 27 Jan 2021, 5 p.m.

Panel Version: 2.274

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 32330417

Green List (high evidence)

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

Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.

Panel Version: 2.491

There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 7 Jul 2020, 4:22 p.m. | Last Modified: 7 Jul 2020, 4:22 p.m.

Panel Version: 2.111

Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 3 unrelated cases, together with supportive Drosophila, demonstating the effects of the variants (PMID 32330417). PMID 20563892 reports a de novo pericentric inversion in chromosome 6 with breakpoints in 6p12.1 and 6q21 reported in a female patient with microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation. Supporting in vitro and drosophila model data also included.
Sources: Literature

Created: 7 Jul 2020, 4:19 p.m. | Last Modified: 7 Jul 2020, 4:21 p.m.

Panel Version: 2.111

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown