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.