Early onset or syndromic epilepsy

Gene: SHANK3

Green List (high evidence)

Comment on list classification: There are numerous individuals reported in literature with heterozygous SHANK3 variants and Phelan-McDermid syndrome. Around 30% of patients reported to date had seizures. Hence, this gene should be promoted to Green on Early onset or syndromic epilepsy.

Created: 8 Jul 2026, 10:22 a.m. | Last Modified: 8 Jul 2026, 10:22 a.m.

Panel Version: 9.27

PMID: 29719671 De Rubeis et al., 2018
Report of 17 individuals with Phelan-McDermid syndrome, and literature review of 60 other previously reported patients. Most mutations were truncating, often de novo, with 4 recurrent variants p.Leu1142Valfs*153, p.Ala1227Glyfs*69, p.Arg1255Leufs*25, and c.2265+1G>A. Seizures were present in 5/17 individuals (29%).

PMID: 36967043 de Coo et al., 2023
Publication is part of European guidelines for Phelan-McDermid syndrome (PMS). In the largest cohort of PMS patients (n=201), prevalence of seizures was 27%. The prevalence goes up with age e.g., seizure onset under age 5yrs was 11%, but 43% between ages 10-18yrs. Pooled prevalence of seizures from 14 PMS studies was 32%. All types of seizures, febrile and non-febrile, have been recorded.
Sources: Literature

Created: 8 Jul 2026, 10:21 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Phelan-McDermid syndrome, OMIM:606232; Phelan-McDermid syndrome, MONDO:0011652

Publications

• 29719671
• 36967043