[source]
pmid = PMID:35386260
title = A de novo PUM1 Variant in a Girl With a Dravet-Like Syndrome: Case Report and Literature Review
[diagnosis]
disease_id = OMIM:620719
disease_label = Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism
[text]
The proband is a 3-year-old girl; she is the second child of non-consanguineous, healthy Chinese parents. Their elder son is healthy, and there is no remarkable medical history of the family. At the time of the birth of the proband, her father and mother were 29 and 28 years old, respectively. She was born at full term with normal delivery. She had normal birth weight (2,950 g), height (49 cm), and occipitofrontal circumference (33 cm).
At 3 months of age, she could hold her head without support. At 4 months, she was able to follow faces and could recognize her mother. At 4 months of age, she experienced an episode of status epilepticus that was triggered by fever every time. The episode continued for ~2 h and was stopped by midazolam administration at the local community hospital. She was then transferred to our hospital for the treatment of status epilepticus. It was observed that during the seizures, her eyes were fixated in a one-sided stare, the right side of her mouth twitched, her right limbs showed stiffening and clonus, and she lost consciousness. These findings persisted for the entire duration of the seizure (2 h). After this seizure, she was reported to have several seizures with a frequency of once per 1–3 months. All these seizures were fever triggered and presented as status epilepticus. She was successively administered courses of levetiracetam (LEV; max dosage at 55 mg/kg.day), valproate (VPA; max dosage at 38 mg/kg.day), and topiramate (TPM; max dosage at 5.2 mg/kg.day); however, no improvement was noted. Perampanel (PER; final dose at 3 mg/day) was added to the combination treatment of LEV, VPA, and TPM at 1 year and 10 months of age, which reduced the frequency of fever-triggered seizures from once a month to only one episode in the last year. It further reduced the seizure duration to 2–3 min. Her development was normal before 4 months of age (held head steady without support and recognized familiar people), and developmental regression was noted after the onset of epilepsy. She started establishing eye contact at 1 year old again and rolling her body at 1 year and 6 months old. She was identified as having profound axial hypotonia and could no longer hold her head after the onset of epilepsy. At the last follow-up when she was 3 years old, gradual developmental improvement was noted, but she had still not begun verbal communication.
She had several dysmorphic features with high-arched palate, ptosis, hypertelorism, broad nasal bridge, low-set ears, bitemporal narrowing, and almond-shaped eyes (Figure 1A). Considering the severe motor delay and hypotonia, she could not be evaluated for ataxia. The background EEG showed diffuse slowing activity initially at 4 months of age. Sporadic multifocal spikes appeared over time in several electroencephalograms taken at different time points (at age ≥11 months), with spike-and-wave discharges noted primarily in the left posterior region of the head. Episodes of focal slow waves were noted in areas of the right parietal, frontal, and temporal lobes (Figures 1B,C). At 11 months of age, bilateral temporal horn of the ventricle was found to be enlarged on brain MRI. Furthermore, a thin corpus callosum was seen (Figures 1D,E), indicating that the white matter may also be affected.
During her last follow-up at 3 years of age, LEV was being tapered, and the other anti-seizure medicines were continued. With these medicines, the seizure frequency had been reduced to once every 5–6 months, and the seizure duration had been reduced to 2–3 min. After the reduction of seizure duration and frequency, no signs of developmental regression were noted. She could now roll over her body and smile at an acquaintance.