Early onset or syndromic epilepsy

Gene: ANKRD11

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: 28 Jan 2021, 4:08 p.m. | Last Modified: 28 Jan 2021, 4:08 p.m.

Panel Version: 2.278

Green List (high evidence)

Nardello et al, 2020 - patient weith severe neurological phenotype of KBG syndrome with a novel het fs de novo variant in ANKRD11. They then compared the epilepsy and EEG data for their patient with patient(s) reported in 7 previous papers (Table 1) - in this small subset of patients similar EEG patterns were seen.

Created: 27 Jan 2021, 3:44 p.m. | Last Modified: 27 Jan 2021, 3:44 p.m.

Panel Version: 2.274

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
KBG syndrome

Publications

• 33476899

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 2:16 p.m. | Last Modified: 20 Oct 2020, 2:16 p.m.

Panel Version: 2.190

Comment on list classification: Added to panel and reviewed Green by Tracy Lester. Although KBG syndrome has variable symptoms, epilepsy can be amongst the phenotypes. Based on literature review and Tracy Lester's review, updated rating from Grey to Green.

Created: 26 May 2020, 2 p.m. | Last Modified: 26 May 2020, 2 p.m.

Panel Version: 2.59

PMID:27900361. Kleyner et al., 2016 describe a 13 yr old male with phenotypes including epilepsy, severe DD, distinct facial features and hand anomalies. Exome sequencing identified a novel de novo heterozygous LOF single bp duplication (c.6015dupA) in ANKRD11, leading to a premature stop codon.

Created: 26 May 2020, 1:58 p.m. | Last Modified: 26 May 2020, 1:58 p.m.

Panel Version: 2.58

PMID:25543316. Samanta et al., 2015 report a 7 yr old boy with a ANKRD11 variant and developmental delay, focal epilepsy and behavioral concerns. He had frequent focal seizures but had enjoyed seizure-free state intermittently up to 9 months. He also had rare secondarily generalized tonic–clonic seizures, less than one episode in a year. After normal EEGs age 1 and 3, an EEG age 5 revealed EEG abnormalities.

Created: 26 May 2020, 1:58 p.m. | Last Modified: 26 May 2020, 1:58 p.m.

Panel Version: 2.58

PMID:30182498. Miao et al., 2019 analysed Chinese Pediatric Epilepsy patients and found a heterozygous de novo p.Arg1462LysfsTer92 ANKRD11 variant in 1 individual.

Created: 26 May 2020, 1:50 p.m. | Last Modified: 26 May 2020, 1:50 p.m.

Panel Version: 2.57

Green List (high evidence)

KBG syndrome - EEG abnormalities, with or without seizures, have been reported in about 50% of affected individuals [Skjei et al 2007]. Age of onset can range from infancy to the teenage years [Low et al 2016]. The type of epilepsy is variable. Although tonic-clonic seizures are most common, no one specific type of epilepsy has been associated with the syndrome. Treatment with antiepileptic medication has proven effective in the majority of affected individuals. Many have remission of symptoms after adolescence [Lo-Castro et al 2013]. A few affected individuals have reportedly had severe seizures at a young age (described as infantile spasms / epileptic encephalopathy), in some cases drug resistant [C Ockeloen, personal communication; Samanta & Willis 2015]. - taken from GeneReviews, KBG syndrome, last updated Mar2018.
Penetrance of KBG syndrome is thought to be complete, but with variable expressivity.
Also associated with 16q24.3 deletions.
Sources: Expert Review

Created: 22 May 2020, 9:20 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
KBG syndrome

Publications

• 29565525