Rationale:
Isodicentric chromosome 15 or inverted duplication of proximal chromosome 15 (idic15), with an incidence of about 1 in 30,000, is the most common genetic disorder attributable to supernumerary marker chromosomes. The resultant clinical syndrome is well described in the literature; patients with this condition present with epilepsy, hypotonia, developmental delay, and autistic features. Refractory epilepsy is a hallmark of idic15, occurring in about 75% of patients. Abnormal brain imaging findings have not been well characterized in association with this syndrome and focal cortical dysplasia specifically has never been reported. The frequency and nature of brain malformations in patients with idic15 should be further investigated, as the presence of anatomical cortical anomalies can have important implications in determining the subsequent management of epilepsy in this patient population.
Methods:
This case report depicts two patients diagnosed with idic15, who presented with the typical sequelae of this syndrome, and specifically reviews their brain MRIs.
Results:
The patients presented here, one girl and one boy, were both diagnosed with medically refractory epilepsy, autism, and global developmental delay. CMA of the female patient revealed quadruplication in the region of 15q11.2-q13.3. She was diagnosed with epilepsy at nine years old, and today requires four anti-seizure medications to achieve seizure control. EEG demonstrated frequent sharp waves in the left frontoparietal region. Brain MRI (Figure 1) showed abnormal cortical folding involving the left central sulcus, superior frontal sulcus, and middle frontal gyrus, spatially corresponding well with the focal abnormalities on EEG. Visualization of these findings required 3D multiplanar reconstruction to correctly align and compare the original images.
CMA of the male patient revealed variable degrees of amplification between 15q13.3 and the pericentromere. He was diagnosed with epilepsy at two years old and continues to have daily seizures despite receiving four anti-seizure medications. Brain MRI (Figure 2) showed T2/FLAIR hyperintensity involving the cortical and subcortical tissue along a left midline frontal lobe gyrus. Surface EEG data was not clearly localizing, as it demonstrated both multifocal and generalized epileptiform abnormalities.
Conclusions:
We present two patients with idic15 and focal cortical dysplasia, an association not previously described in the literature, which may suggest a contributing structural etiology of their epilepsy and thus offer a potential surgical target. Further characterization of imaging findings in idic15 is needed.
Funding: None.