Abstracts

Rationale: The 15q11.2 BP1–BP2 microdeletion syndrome is an emerging condition in human related to neurodevelopmental diseases, with changes in cognition, behavior, and brain morphology. Other uncommon clinical features are seizures/epilepsy, autism spectrum disorder, attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD), schizophrenia/paranoid psychosis, and motor delay. The 15q11.2 BP1-BP2 encompasses four protein-coding genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5), which are associated with PWS, ASD, schizophrenia, and epilepsy. But 15q11.2 microdeletion associated with severe epileptic encephalopathy was rarely reported.

Methods: We report three cases from unrelated families with 15q11.2 BP1-BP2 microdeletion who presented with global developmental delay, hyperekplexia, and different intractable epileptic syndromes.

Results: Case 1: 15-month-old male with developmental delay, spastic quadriplegic CP, and West syndrome. Seizure onset was at 3 months of age with epileptic spasm. Interictal EEG showed hypsarrhythmia pattern and ictal EEG showed 2 Hz delta activity superimposed with fast activity, followed by cerebral attenuation. MRI brain showed bilateral anterior and posterior perisylvian polymicrogyria involving frontal, temporal and parietal lobes and periventricular nodular gray matter heterotopia. Chromosomal microarray shows a heterozygous 483 Kb deletion involving chromosome 15q11.2.

Case 2: 7-year-old male with developmental delay, microcephaly, spastic quadriplegic CP, and late onset Lennox-Gastaut syndrome. The seizure onset was 5 years of age with clusters of tonic seizures and epileptic spasms, and generalized tonic clonic seizures. The EEG showed frequent multifocal epileptiform discharges, bursts of generalized, slow spike waves at 2.5 Hz, and periods of generalized paroxysmal fast activity with relative voltage attenuation. MRI brain showed diffuse volume loss, multifocal bilateral polymicrogyria, and cerebella hypoplasia. Chromosomal microarray shows a heterozygous 385 Kb deletion involving chromosome 15q11.2.

Case 3: 7-year-old male with spastic quadriplegic CP, autism, and likely Angelman syndrome. The seizures onset was at 12 months of age with staring spells, then developed atonic seizures, and generalized tonic clonic seizures after 2 years of age. The EEG was normal at 12 months of age, then the EEG showed frequent runs of 2-3 Hz generalized or posterior rhythmic delta slowing at 2 years of age, and frequent rhythmic 3-4 Hz notched delta/theta complex in the left or right posterior head regions, and occasional to frequent periods of relative voltage attenuation with/without superimposed fats activity up to 6 seconds. MRI brain was normal. Chromosomal microarray shows a heterozygous 534 Kb deletion involving chromosome 15q11.2.

Conclusions: Our three new cases further confirm some of the clinical features associated with 15q11.2 BP1–BP2 deletion. It also expands its epileptic phenotype, as well as brain structural abnormalities associated with 15q11.2 deletion.

Funding: Please list any funding that was received in support of this abstract.: None.