Table 1 Clinical characteristics of patients reported with similar NEUROD2 variants
Characteristics | Sakpichaisakul et al., 2022 (this study) | Sega et al., 2019 | Runge et al., 2021 |
|---|---|---|---|
NEUROD2 variant | c.388G > C, p. E130Q | c.388G > C, p. E130Q | c.388G > C, p. E130Q |
Inheritance | De novo | De novo | De novo |
Sex | Female | Female | Male |
Birth weight (g), length (cm), head circumference (cm) | 4500, 55, 36 | 3175, NA, NA | 3175, 51.4, 31.8 |
Age at last examination | 27 months | 5 years | 21 months |
Weight, height, and head circumference at last examination | 50th -75th, 50th, <3rd percentile | 3rd –10th, 3rd, <3rd percentile | 9.48 kg, 81.5 cm, 43.5 cm (<  1 percentile) |
Failure to thrive | No | Yes | No |
Onset of developmental delay (months) | 2–4 | 2–4 | NA |
Onset of seizure (months) | 5 | 5 | 4 |
Seizure type | Epileptic spasms | Epileptic spasms | Epileptic spasms |
Initial EEG features | Multifocal epileptiform discharges | Hypsarrhythmia | NA |
ASM previously tried | Vigabatrin, prednisolone, zonisamide | ACTH, prednisolone, pyridoxine, vigabatrin | NA |
Seizure freedom | Yes, seizure free since the age of 22 months, currently on vigabatrin and zonisamide | Seizure free since the age of 2.5 years. Started on the ketogenic diet at 16 months, discontinued at 3 years | NA |
Last EEG after being seizure-free | Intermittent epileptiform discharges over the bilateral posterior head regions. | Intermittent epileptiform discharges over the left temporal region and excessive slow waves over bilateral occipital regions during sleep, no electrographic seizures. | NA |
Brain MRI features | At 6 months: increased T2/FLAIR signal intensity with restricted diffusion in bilateral globus pallidus. MRS: decreased NAA and presence of small lactate peak At 24 months: symmetric hypersignal T2/FLAIR lesions without restricted diffusion in the central tegmental tract, delayed myelination in bilateral fronto-temporal lobes, and small right hippocampus. | At 6 months: delayed myelination and thin corpus callosum. At 12 months: asymmetrical increased T2 signal intensity in bilateral parietal white matter, thin corpus callosum, prominent frontotemporal CSF spaces, improved myelination. At 3.5 years: bilateral increased T2 signal intensities in putamina, parietal periventricular white matter, diffuse thinning of corpus callosum, normal myelination. | NA |
Walking delay | Yes, currently stands alone, walks with support | Yes, still needs a walker | Most likely, yes (not yet) |
Intellectual disability | Yes | Yes, severe cognitive dysfunction, is not able to understand simple commands | Yes |
Speech disturbance | Yes, speaks one word | Yes, 5 single words only, no sentences | Yes, delayed |
Autistic features/behavioral disorder | Yes, limited social interaction and repetitive behavioral patterns | NA | ASD |
ADHD/aggressiveness | No | Yes, hyperkinetic movements | No |
Physical exam features | Bilateral esotropia, anisocoria, repetitive hand and mouth movements | Bilateral esotropia, hyperkinetic movements | Microcephaly, hypotonia, global developmental delay, feeding difficulties, constipation |