Exploration of Neuroprotective Therapy

Table 2. Summary of published NEUROD2 cases (2019–2024)^*.

Case	Reference	Sex	Variant (cDNA)	Variant (protein)	Inheritance	Age at onset	Epilepsy	Developmental/Behavioural features	EEG/Cerebral MRI (brief)	Other features	Treatment/Outcome
1	[5]	F	c.(388G>C)	p.Glu130Gln	de novo	Infancy	DEE/Infantile-spasms	Severe global DD, hypotonia	Abnormal EEG; MRI: hyper-intensity of the putamen and white matter, corpus callosum thinning	Hyperkinetic movements	ASM; ketogenic diet; persistent seizures
2	[5]	M	c.(401T>C)	p.Met134Thr	de novo	Infancy	DEE/Infantile spasms	Severe global DD	Abnormal EEG; MRI: diffuse cerebral volume loss	Dysphagia	ASM; poor control
3	[6]	M	c.(488T>C)	p.Leu163Pro	de novo	Adolescent	No epilepsy	Global DD; ID	Normal EEG: MRI: normal	Ventricular septal defect; caffè-au lait spot	Supportive therapies
4	[6]	F	c.(703G>A)	p.Ala235Thr	Parental data unavailable	Adolescent	No epilepsy	DD; ASD	NA	NA	Supportive/Surveillance
5	[8]	F	c.(385C>T)	p.Arg129Trp	de novo	Infancy	No epilepsy	DD/ID ± ASD	Abnormal EEG; MRI: hyper-intensity of the putamen and white matter, corpus callosum thinning	Central obesity, large central teeth, tapering fingers	Supportive therapies
6	[8]	M	c.(388G>C)	p.Glu130Gln	de novo	Infancy	DEE/Infantile spasms	DD/ID ± ASD	Abnormal EEG; MRI diffuse cerebral atrophy	Dysphagia, microcephaly	ASM; symptomatic
7	[8]	M	c.(804 C>A)	p.Arg268Trp	From the affected father (patient 8)	Childhood	No epilepsy	DD/ID ± ASD	NA	Inverted nipples; aggressive behaviour	Symptomatic
8	[8]	F	c.(804 C>A)	p.Arg268Trp	Parental data unavailable	Adult	No epilepsy	Mild ID	NA	NA	NA
9	[7]	F	c.(388G>C)	p.Glu130Gln	de novo	Infancy	DEE/Infantile spasms	Global DD; later ASD traits	EEG: multifocal t spikes; MRI: delayed myelination, hyperintensity in globi pallidi and central tegmental tracts	NA	Vigabatrin + high-dose prednisolone; Relapsing-remitting epilepsy
10	[9]	F	c.(388G>A)	p.Glu130Lys	de novo	infancy	Rett-like features	Severe DD, stereotypies, Rett-like phenotype	EEG/MRI abnormalities	NA	Symptomatic
11	[10]	F	c.(388G > C)	p.Glu130Gl)	de novo	infancy	DEE/infantile spasms	DD/ID; dysmorphic features	EEG: hypsarrhythmia/MRI: no structural abnormalities	NA	ASM; prednisone; partial response described
12	Present case	F	c.(790G>A)	p.Ala264Thr	de novo	Neonatal	Neonatal hypotonia; neonatal seizures	DD/ASD trait	EEG poorly structured/MRI: subcortical white matter hyperintensity	Pelvic kidney; Dysphagia	Levetiracetam; symptomatic

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ASD: autism spectrum disorder; ASM: anti-seizure medication; DD: developmental delay; DEE: developmental and epileptic encephalopathy; ID: intellectual disability; MRI: magnetic resonance imaging; NA: not available. ^*Two patients with chromosome deletion including the NEUROD2 gene, described by Runge et al. [8], are not included in the table.

Declarations

Acknowledgments

The authors wish to thank the patient’s family for their collaboration, the medical and nursing staff involved in the patient's care for their dedication, and the Department of Maternal-Infant and Adult Medical and Surgical Sciences for its continued research support.

Author contributions

LL: Conceptualization, Investigation, Formal analysis, Visualization, Writing—original draft, Writing—review & editing. IG: Investigation, Writing—original draft, Writing—review & editing. CR: Investigation, Writing—original draft, Writing—review & editing. NB: Investigation, Writing—original draft, Writing—review & editing. MB: Investigation, Writing—original draft, Writing—review & editing. VC: Investigation, Writing—original draft, Writing—review & editing. EB: Investigation, Writing—original draft, Writing—review & editing. MP: Validation, Writing—review & editing, Supervision. AB: Validation, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

This study was conducted in accordance with the principles of the Declaration of Helsinki. According to institutional policy and Italian national regulations, formal ethics committee review is not mandatory for retrospective case reports describing routine clinical practice, provided no experimental interventions are performed, and no additional biological samples are collected beyond those obtained for standard diagnostic purposes. All data presented in this report were obtained as part of routine clinical care.

Consent to participate

Informed consent to participate in the study was obtained from the patient’s parents.

Consent to publication

Written informed consent for publication of clinical details and genetic findings was obtained from the patient’s parents. Patient data were anonymized and handled in strict compliance with the European Union General Data Protection Regulation (GDPR) (EU 2016/679) and Italian privacy law.

Availability of data and materials

The datasets supporting the findings of this study are available from the corresponding author upon reasonable request.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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