Early onset or syndromic epilepsy

Gene: NSD1

I don't know

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

Green List (high evidence)

AD Sotos syndrome - characterised by excessively rapid growth, acromegalic features and a non-progressive cerebral disorder with MR. nonspecific EEG changes and seizures have been observed. Microdeletionsof 5q35 as well as point mutations. Tatton-Brown et al, 2005 - table 3 showing clinical features of patients with recurring NSD1 mutations - 14/51 had seizures reported as part of the phenotype. They class seizures as a major feature.

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
Leukemia, acute myeloid, 601626; Sotos syndrome 1, 117550

Publications

• 23592277

Comment on list classification: Promoted from amber to green. NSD1 is confirmed to be associated with Sotos syndrome on OMIM and Gene2Phenotype, and both databases have listed seizures as a phenotype. GeneReviews stated that ~25% of Sotos syndrome patients have seizures. A large multicentre gene-phenotype association study showed that there are multiple cases (>3) of Sotos syndrome patients who have seizures.

Created: 29 Nov 2018, 12:13 p.m.

Green List (high evidence)

Around 25% of individuals with Sotos syndrome have seizures.

Created: 17 Aug 2018, 11:19 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Sotos syndrome

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