Early onset or syndromic epilepsy
Gene: NTRK2
AD EIEE 58 - onset of refractory seizures in first few days or months of life. Hamdan et al, 2017 - 4 unrelated children - seizures were generalised infantile spasms, focal or of multiple types and were difficult to control. All had a de novo het missense variant Y434C. No functional work done.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epileptic encephalopathy, early infantile, 617830; Obesity, hyperphagia, and developmental delay 613886
Publications
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Updated rating from Grey to Green: Added and reviewed Green by Konstantinos Varvagiannis. Although probable rating in DD-G2P for 'Epilepsy and ID', there are sufficient unrelated cases (>3) of patients with NTRK2 variants and seizures from PMID:29100083 and PMID:15494731 (2 variants) for both EE and obesity/hyperphagia phenotypes.Created: 11 Dec 2018, 11:25 a.m.
In 4 unrelated patients with early infantile epileptic encephalopathy-58 (MIM:617830), Hamdan et al. (PMID:29100083, 2017) identified a de novo heterozygous transition (c.1301A-G, NM_006180.4, Tyr434Cys) in the NTRK2 gene.
Patient in Yeo et al (PMID:15494731) with obesity and hyperphagia had a history of absence seizures in second and third years of life only.Created: 11 Dec 2018, 11:21 a.m.
Heterozygous pathogenic variants in NTRK2 cause Epileptic encephalopathy, early infantile, 58 (EIEE58 - MIM 617830) or Obesity, hyperphagia, and developmental delay (MIM 613886).
Seizures can be noted in individuals falling into either diagnosis [eg. observed in the individuals with obesity and hyperphagia as in PMIDs: 15494731 and 29100083 (individual with Thr720Ile)].
Concerning EIEE58 Tyr434Cys appears to be a recurrent variant that has been observed in 4 unrelated individuals (summary in table 2 from PMID: 29100083).
NTRK2 is a probable DD gene in G2P associated with epilepsy and ID.
As a result, this gene can be considered for inclusion in this panel as green.
Sources: LiteratureCreated: 10 Dec 2018, 5:31 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 58 (MIM 617830); Obesity, hyperphagia, and developmental delay (MIM 613886)
Publications
Source Wessex and West Midlands GLH was added to NTRK2.
Source NHS GMS was added to NTRK2.
Konstantinos Varvagiannis: Heterozygous pathogenic varian
Gene: ntrk2 has been classified as Green List (High Evidence).
Gene: ntrk2 has been classified as Green List (High Evidence).
gene: NTRK2 was added gene: NTRK2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: NTRK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NTRK2 were set to 29100083; 15494731 Phenotypes for gene: NTRK2 were set to Epileptic encephalopathy, early infantile, 58 (MIM 617830); Obesity, hyperphagia, and developmental delay (MIM 613886) Penetrance for gene: NTRK2 were set to unknown Review for gene: NTRK2 was set to GREEN