Clinical Report
A previously healthy 3-month-old baby girl presented to our hospital with a 3-week history of episodes of loss-of-contact of brief duration, then evolved into focal seizures, characterized by deviation of the head and gaze to the right and hypertonia of the ipsilateral limbs. Parents were healthy, non-consanguineous Caucasians. Maternal and paternal undefined family history of epilepsy was reported. Pregnancy and delivery were normal. She had normal motor milestones. Vaccinations were not on schedule and she did not have a significant health problem up to date. At the initial examination in the paediatric unit, she was in the 50th percentile for weight, 90thpercentile for length and 10-25th percentile for head circumference. No hypo- or hyperchromic patches were evident. Vital signs were within normal ranges according to her age (body temperature, heart rate, breath rate, blood pressure, oxygen saturation). She was fully awake with eye contact, without apparent nystagmus. There were no skeletal anomalies and muscular trophism was normal. On detailed neurological examination, pupils were isocoric with a bilateral normal light reflex. Cranial nerves’ function was normal, with no facial asymmetry. She had a mild hypotonia of the trunk. Patellar reflexes were present bilaterally. Laboratory investigations, including complete blood count, biochemical parameters, arterial blood gas and coagulation profile, were normal. Tandem mass spectrometry, urine and blood aminoacid profile and urine organic acid profile, carried-out in order to exclude inborn errors of metabolism, were all normal; as well as ECG, echocardiography and abdomen ultrasound. A first EEG examination showed spikes/spikes waves starting from the temporal region with secondary generalization. Therapy with Levetiracetam and vitamin B6 was started without benefit. In the following days, she started to presented frequent seizures (i.e. 15/day) which evolved in spasms in flexion, with duration varying from two to ten minutes. A video-EEG was then performed and a right hemi-hypsarrhythmia was noticed. Brain MRI disclosed a complex brain malformation, with asymmetry of the hemispheres (right>left) with asymmetric ventricles, polymicrogyria of the right anterior mesial frontal cortex, cortical dysplasia, multiple focal areas of cortical heterotopias along the walls of the right lateral ventricle, the largest in the paratrigonal area (Figures 1-2). A marked and uniform thinning of the corpus callosum was also documented, with considerable hypotrophy of the knee (Figure 3). There was also a distorted and dysmorphic appearance of the supratentorial ventricular cavities with extension of the bifrontal-bitemporal periencephalic liquor spaces. ACTH therapy was then performed (0,2 mg im once a day and then every other day) with initial resolution of seizures and significant improvement of control EEGs. When ACTH was withdrawn, focal seizures reappeared. They were characterized by deviation of the ocular globes to the right and loss of contact of variable duration, especially evident on awakening and falling, often in cluster. A new EEG was performed and it showed asymmetric basic activity with low-turned sharp elements on frontal regions of the right hemisphere. Topiramate was then added to the therapy, at the initial dosage of 1 mg/kg. Due to pressure values at the upper limits, Levetiracetam was suspended and Vigabatrin therapy undertaken. To complete the diagnostic work-up, an ophthalmological evaluation was performed with evidence of pathological excavation of the right optical disc with small inferior coloboma and peripapillary retinal areas of chorioretinal atrophy. Visual and auditory evocative potentials were normal. The baby girl was discharged from our department with frequent follow-up controls as an outpatient. At the age of 9 months the child presented a delay in psychomotor development and she does not maintain the sitting position on its own. To clinical re-evaluation we noticed a dystonic posture of the hand. A new ophthalmological evaluation showed a peripapillary pigmentary ring and areas of pigmentend atrophy (corioretinal gaps). She was on therapy with Topiramate (5mg/kg/day) and Vigabatrin (100mg/kg/day) with moderate seizures control. Submitted to array-CGH analysis and to a NGS-gene panel for epilepsy and cortical malformations, the girl was found as harboring two variants in trans (compound heterozygosis) of theDCHS1 gene, never reported in literature and databases.