Medical Student SUNY Upstate Medical University Bethpage, New York
Rationale: The 2q24.2-24.3 chromosome region encodes the cluster of sodium channel genes, which are important in severe childhood epilepsy phenotypes such as Dravet syndrome and migrating partial seizures of infancy. SCN1A variants are a frequent cause of Dravet syndrome. Variants of other genes in the cluster, SCN2A and SCN3A, have been implicated in complex phenotypes including migrating partial seizures of infancy. However, the roles of other genes, either within the SCN cluster (such as SCN7A or SCN9A) or in the segments proximal to it, have not been clearly delineated. We suspect that these additional gene deletions contribute to the complex phenotype of a patient with medically refractory epilepsy. Methods: Extensive genetic, metabolic and electrodiagnostic studies were undertaken. A SNP-microarray showed a 4,259 kbp deletion of the long arm of chromosome 2 at band q24.2-24.3 in 98% of our patient’s cells. A 118 kbp deletion of the short arm of chromosome X at band p11.23 was also detected. According to the Invitae epilepsy panel, some deleted genes include SCN1A, SCN2A, SCN3A, SCN7A, SCN9A, COBLL1, GRB14 and SLC38A11. Results: This patient is the product of non-consanguineous parents via in vitro fertilization with an uncomplicated full term pregnancy and delivery. His seizures began as febrile seizures at eight months of age and have become intractable. These episodes are characterized by clusters of focal motor seizures occurring up to 60 times a month. They are exacerbated by fevers due to vaccinations or upper respiratory infections. In addition to his seizures, our patient has significant hypotonia and dysphagia at baseline. He has apnea requiring supplemental oxygen after his more severe seizures that is associated with cyanosis and discoloration of his extremities. He also has profound developmental delay. At 15 months of age, he cannot babble, point or sit unsupported for long. He is on valproate, cannabidiol, and clobazam and now has approximately 15 seizures per month. However, he continues to have clusters of seizures requiring hospitalization and intubation. Conclusions: We speculate that the extent of the 2q24.2-2q24.3 deletion plays a role in the severity of our patient’s presentation. Patients who have different deletions within this region of chromosome 2 have demonstrated a variety of clinical presentations, including generalized hypotonia with or without seizures. Furthermore, there are patients exhibiting larger deletions of the 2q24.3-2q31.1 region who have atonic and hypomotor seizures. While some cases share similarities with our patient, no case captures all of his clinical features. Our unique case emphasizes that the severity and complexity of the epilepsy phenotype is influenced by the extent of the deleted segments including and adjacent to the sodium gene cluster. Funding: Please list any funding that was received in support of this abstract.: No funding.
