Epilepsy, X-linked, with Variable Learning Disabilities and Behavior Disorders via the SYN1 Gene

Synapsin I-related X-linked epilepsy with variable learning disabilities and behavior disorders is a rare neurological disorder. The phenotype includes various combinations of epilepsy, macrocephaly, learning difficulties, aggressive behavior or autism with low penetrance (Garcia et al 2004; Fassio et al 2011).

Epilepsy is present in virtually all the male patients. Learning and behavioral disturbances are common among male patients, while only a few males have autism spectrum disorders. Female carriers have normal intelligence and have no record of seizures or aggressive behavior (Garcia et al 2004).

Pathogenic variants in the SYN1 gene are causative for synapsin I-related X-linked epilepsy with variable learning disabilities and behavior disorders, which is inherited in an X-linked recessive manner. This gene is also a predisposing gene to autism spectrum disorders. The SYN1 gene encodes synapsin I, a synaptic vesicle associated protein that may play an important role in neurotransmitter release, synaptogenesis, maintenance of mature synapses and plasticity and neuronal development (Garcia et al 2004; Fassio et al 2011; Cesca et al 2010).

Pathogenic variants in SYN1 include nonsense and missense variants only. No large deletions/duplications in the SYN1 locus have been reported (Garcia et al 2004; Fassio et al 2011; Human Gene Mutation Database).

Synapsin I-related X-linked epilepsy with variable learning disabilities and behavior disorders is a rare disease. However, certain missense pathogenic variants were discovered in 1.0 and 3.5% of French-Canadian patients with epilepsy and autism, respectively (Fassio et al 2011).

No large deletions or duplications involving the SYN1 gene have been reported (Human Gene Mutation Database).

This test provides full coverage of all coding exons of the SYN1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.