Developmental and Epileptic Encephalopathy 89 (DEE89): Disease Characteristics Report

Executive summary and evidence limits

Developmental and epileptic encephalopathy 89 (DEE89) is an ultra-rare, autosomal-recessive neurodevelopmental disorder caused by biallelic loss-of-function variants in GAD1, which encodes glutamate decarboxylase 67 (GAD67), the principal enzyme supporting basal γ-aminobutyric acid (GABA) production in the central nervous system. The defining phenotype is early-infantile epilepsy followed by—or accompanied by—severe developmental impairment, hypotonia or weakness, and occasional craniofacial or skeletal abnormalities. The disease was established from only six unrelated affected individuals, so most percentages below describe that ascertainment cohort rather than population-level frequencies. (neuray2020earlyinfantileonsetepilepsy pages 3-3, neuray2020earlyinfantileonsetepilepsy pages 1-1, OpenTargets Search: developmental and epileptic encephalopathy 89-GAD1)

The foundational primary report is Neuray et al., “Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants,” published online 10 July 2020 in Brain, volume 143, pages 2388–2397; PMID 32282878; DOI/URL: https://doi.org/10.1093/brain/awaa178. Its abstract states: “Mice lacking GAD1 show neonatal mortality, but the human phenotype associated with GAD1 disruption is poorly characterized. Neuray et al. describe six patients with biallelic GAD1 mutations, presenting with early-infantile onset epilepsy, neurodevelopmental delay, muscle weakness and non-CNS manifestations.” No substantive 2023–2024 DEE89-specific cohort, natural-history study, treatment trial, or mechanistic patient study was identified; recent literature largely discusses DEEs generally rather than expanding this disease-specific evidence base. (neuray2020earlyinfantileonsetepilepsy pages 3-3, neuray2020earlyinfantileonsetepilepsy pages 1-1)

Table: This table summarizes the highest-confidence evidence gathered for developmental and epileptic encephalopathy 89, preserving small-cohort denominators and highlighting where the literature is strong versus sparse. It is useful as a compact evidence map for knowledge-base curation.

1. Disease information

Definition

DEE89 is a monogenic developmental and epileptic encephalopathy in which the underlying GAD1 defect directly disrupts neurodevelopment while deficient inhibitory neurotransmission promotes epilepsy. The “developmental and epileptic” designation is important: developmental disability is not merely a consequence of recurrent seizures. In the original cohort, severe intellectual/developmental impairment persisted in all patients even though three became seizure-free, supporting parallel developmental and epileptic effects. (neuray2020earlyinfantileonsetepilepsy pages 6-6)

Identifiers and synonyms

• MONDO: MONDO:0030856.
• OMIM phenotype: 619124.
• Causal gene: GAD1, Ensembl ENSG00000128683; approved name glutamate decarboxylase 1.
• Common names: developmental and epileptic encephalopathy 89; DEE89; GAD1-related developmental and epileptic encephalopathy; GAD1-related early-infantile epilepsy and developmental delay.
• Orphanet: no disease-specific Orphanet identifier was established in the retrieved evidence.
• ICD-10/ICD-11: no unique DEE89 code. Cases are coded under broader genetic/developmental epileptic encephalopathy, epilepsy, intellectual disability, and developmental-disorder categories.
• MeSH: no unique disease heading; broader headings include Epileptic Encephalopathies, Epilepsy, and Neurodevelopmental Disorders.

Open Targets links MONDO:0030856 to one associated target, GAD1, and cites PMID 32282878 plus ClinVar records, providing aggregated disease-level corroboration of the primary case-series evidence. (OpenTargets Search: developmental and epileptic encephalopathy 89-GAD1)

Source granularity: available information is mainly an aggregated publication-level case series, not longitudinal EHR evidence. Database entries subsequently aggregate those individual reports.

2. Etiology, risk, and protective factors

Causal factor

The established cause is germline biallelic GAD1 variation, generally producing loss of GAD67 function. Five of six reported families had homozygous variants and one had compound-heterozygous variants. Four affected individuals were born to consanguineous parents. (neuray2020earlyinfantileonsetepilepsy pages 3-3)

Risk factors

• Genetic: two pathogenic or likely pathogenic alleles in trans are the principal risk factor. Parental consanguinity increases the probability that both parents carry the same rare allele, but is not mechanistically required.
• Family history: affected siblings would be expected in some families under recessive inheritance, although the founding report comprised one characterized patient per unrelated family.
• Environmental, infectious, lifestyle, age, or sex risk: none has been demonstrated. The reported patients represented diverse ancestries—Persian, Pakistani, African American, Sudanese, Egyptian, and Turkish—arguing against restriction to one population, but the sample is too small for demographic inference. (neuray2020earlyinfantileonsetepilepsy pages 1-2)

Protective factors and gene–environment interaction

No protective allele, modifier gene, diet, exposure, or validated gene–environment interaction is known. Fever, sleep deprivation, illness, or medication nonadherence may trigger seizures in epilepsy generally, but these should not be entered as DEE89 causal factors without disease-specific evidence. Likewise, adequate vitamin B6 is required biochemically for pyridoxal-5′-phosphate-dependent decarboxylases, but neither pyridoxine deficiency nor pyridoxine responsiveness has been demonstrated as a DEE89 mechanism or treatment.

3. Phenotypes

Observed frequencies are from n=6 and therefore have very wide uncertainty.

These features and frequencies derive from the original six-person series. EEG abnormalities included burst suppression, hypsarrhythmia, and diffuse slowing with multifocal or generalized sharp waves; MRI was nonspecific and often normal. (neuray2020earlyinfantileonsetepilepsy pages 3-3, neuray2020earlyinfantileonsetepilepsy pages 4-5)

Quality-of-life impact: no EQ-5D, SF-36, PROMIS, caregiver-burden, or disease-specific QoL measurements have been published. Nevertheless, severe communication, motor, cognitive, and seizure impairments imply dependence for daily activities and substantial caregiver burden. That conclusion is clinical inference, not a measured DEE89 outcome.

4. Genetic and molecular information

Gene and protein

GAD1 encodes the 67-kDa glutamate decarboxylase isoform, GAD67. The protein has an N-terminal targeting/dimerization region, a central pyridoxal-5′-phosphate-binding region, and a C-terminal catalytic region. GAD67 supplies approximately 90% of constitutive basal CNS GABA, whereas GAD65 has a more activity-responsive presynaptic role. (neuray2020earlyinfantileonsetepilepsy pages 1-2, neuray2020earlyinfantileonsetepilepsy pages 1-1, neuray2020earlyinfantileonsetepilepsy pages 5-6)

Suggested annotations include HGNC:4092 (GAD1), UniProt Q99259, and enzyme class glutamate decarboxylase, EC 4.1.1.15. The biochemical reaction is L-glutamate → GABA + CO₂, requiring pyridoxal 5′-phosphate (ChEBI:18405) as cofactor; substrates/products include L-glutamate (ChEBI:29985) and 4-aminobutanoate/GABA (ChEBI:16865).

Reported disease alleles

Seven ultrarare germline variants were reported:

1. c.87C>G, p.(Tyr29Ter) — nonsense.
2. c.568delC, p.(Gln190SerfsTer11) — frameshift.
3. c.670delC, p.(Leu224SerfsTer5) — frameshift.
4. c.971T>G, p.(Phe324Cys) — missense.
5. c.1040C>T, p.(Thr347Met) — missense.
6. c.1591C>T, p.(Arg531Ter) — nonsense.
7. c.1691A>G, p.(Asn564Ser) — missense. (neuray2020earlyinfantileonsetepilepsy pages 6-6)

The truncating variants are expected to cause nonsense-mediated decay or truncated protein. Missense substitutions affect conserved functional regions and were computationally predicted to impair stability or catalysis; four of seven reported alleles involved the PLP-binding domain. The aggregate disease mechanism is therefore loss of function, not gain of function or dominant-negative activity. (neuray2020earlyinfantileonsetepilepsy pages 6-6, neuray2020earlyinfantileonsetepilepsy pages 5-6)

The source paper described the variants as ultrarare and GAD1 as intolerant of damaging variation, but exact gnomAD/TOPMed allele counts and current per-variant ClinVar classifications were not available in the retrieved full-text evidence. These should be refreshed directly from ClinVar and gnomAD before production curation. Open Targets identified two associated ClinVar records, RCV006436612 and RCV004820862. (OpenTargets Search: developmental and epileptic encephalopathy 89-GAD1)

Other genomic mechanisms

No disease-causing recurrent copy-number variant, translocation, inversion, repeat expansion, mitochondrial variant, somatic mosaicism, modifier gene, methylation signature, or other DEE89-specific epigenetic abnormality is established. Large deletions disrupting both GAD1 alleles would be mechanistically plausible but were not documented in the founding cohort.

5. Environmental information

DEE89 is a genetic Mendelian disease. No toxin, radiation, pollution, occupational exposure, smoking, alcohol, diet, infection, or other environmental exposure has been shown to cause it. There is no zoonotic or infectious component. Environmental conditions may alter seizure threshold nonspecifically, but no DEE89-specific interaction has been quantified.

6. Mechanism and pathophysiology

Causal chain

1. Upstream genetic lesion: biallelic damaging GAD1 variants produce absent or impaired GAD67.
2. Primary biochemical defect: reduced PLP-dependent decarboxylation of glutamate to GABA.
3. Cellular effect: diminished GABA supply in inhibitory neurons compromises inhibitory synaptic transmission and maturation of GABAergic networks.
4. Circuit effect: excitation–inhibition imbalance and network hypersynchrony lower seizure threshold, generating early-infantile epilepsy and encephalopathic EEG patterns.
5. Developmental effect: GABA is also a developmental signal affecting neuronal migration, synaptogenesis, and circuit maturation. Thus GAD67 deficiency can directly impair cognition and motor development independently of seizure burden.
6. Downstream clinical manifestations: seizures, severe developmental/intellectual disability, absent speech, hypotonia/weakness, and occasionally cerebral atrophy.
7. Extraneural development: GAD1 expression in embryonic limb mesenchyme and pharyngeal structures, together with reduced fetal movement, may contribute to skeletal abnormalities and cleft palate; the human evidence remains provisional. (neuray2020earlyinfantileonsetepilepsy pages 8-9, neuray2020earlyinfantileonsetepilepsy pages 6-7, neuray2020earlyinfantileonsetepilepsy pages 1-1)

The observation that all six patients remained severely impaired while three achieved seizure control is an important human “natural experiment”: suppressing seizures alone does not reverse the upstream neurodevelopmental defect. (neuray2020earlyinfantileonsetepilepsy pages 6-6)

Ontology-ready mechanism annotations

• GO biological process: glutamate decarboxylation to GABA; GABA biosynthetic process (GO:0009449); gamma-aminobutyric acid signaling pathway (GO:0007214); chemical synaptic transmission (GO:0007268); regulation of membrane potential (GO:0042391); nervous-system development (GO:0007399).
• GO molecular function: glutamate decarboxylase activity (GO:0004351); pyridoxal-phosphate binding (GO:0030170).
• GO cellular component: cytosol (GO:0005829), neuron projection (GO:0043005), presynapse (GO:0098793).
• Cell Ontology: neuron (CL:0000540); GABAergic neuron (CL:0000617); interneuron (CL:0000099). Particular interneuron subclasses have not been shown to be selectively vulnerable in DEE89.

There is no DEE89-specific evidence for apoptosis, autophagy, primary mitochondrial failure, immune activation, chronic inflammation, or a distinct metabolic signature beyond deficient GABA biosynthesis. No patient-derived transcriptomics, proteomics, metabolomics, lipidomics, single-cell, spatial-transcriptomic, multi-omic, CRISPR-screen, iPSC, or organoid study was found.

7. Anatomical structures affected

The central nervous system is primary, especially neuronal networks of the cerebral cortex and other GABAergic circuits. Suggested anatomy terms are brain (UBERON:0000955), cerebral cortex (UBERON:0000956), central nervous system (UBERON:0001017), and synapse (UBERON:0001035). No consistent focal lesion or lateralization has been reported; effects are presumed bilateral and network-wide.

Secondary or variably involved structures include skeletal muscle function, axial skeleton, digits, palate, and craniofacial structures. Weakness may reflect central hypotonia rather than primary myopathy; biopsy or EMG evidence for a muscle-intrinsic lesion is absent. Relevant subcellular sites are cytosol and inhibitory synaptic compartments, not mitochondria, lysosome, or nucleus as primary disease organelles. (neuray2020earlyinfantileonsetepilepsy pages 8-9, neuray2020earlyinfantileonsetepilepsy pages 3-3)

8. Temporal development and natural history

• Prenatal/congenital: most affected infants were not recognized prenatally; cleft palate or skeletal abnormalities may be congenital in a minority.
• Onset: seizures began at 2–6 months, an early-infantile, generally subacute presentation.
• Early course: epileptic spasms, focal motor seizures, or bilateral motor seizures occur with markedly abnormal EEG.
• Later course: severe developmental delay, speech impairment, and weakness become prominent. Seizures may remit with medication or remain drug-resistant.
• Duration: presumed lifelong. No validated staging system exists.
• Remission: seizure freedom occurred in 3/6, but developmental disability persisted; 3/6 remained drug-resistant. (neuray2020earlyinfantileonsetepilepsy pages 3-3)

No longitudinal cohort defines progression rate, regression frequency, adult phenotype, critical therapeutic window, or late complications. Early infancy is nevertheless a plausible intervention window because both seizures and GABA-dependent circuit development are active then; this remains expert mechanistic inference rather than trial evidence.

9. Inheritance and population

Inheritance

Inheritance is autosomal recessive. For two confirmed heterozygous carrier parents, each pregnancy has an expected 25% probability of an affected child, 50% probability of an unaffected carrier, and 25% probability of an unaffected non-carrier. Penetrance for clearly biallelic null or severely damaging genotypes appears high, but cannot be estimated formally. Expressivity is variable, particularly for seizure control, MRI abnormalities, weakness, and extracerebral features.

There is no evidence for anticipation. Germline mosaicism is not required to explain recurrence but remains a theoretical residual risk if a variant appears de novo. No founder effect or carrier-frequency estimate is established. Consanguinity was present in 4/6 founding families, reflecting recessive ascertainment rather than proof of a population-specific disease. (neuray2020earlyinfantileonsetepilepsy pages 3-3, neuray2020earlyinfantileonsetepilepsy pages 1-2)

Epidemiology

No prevalence, incidence, sex ratio, life-table, regional distribution, or ancestry-specific rate is available. Six ethnically diverse unrelated cases were reported initially. DEE89 should therefore be described as ultra-rare, prevalence unknown, not assigned a numerical population rate. (neuray2020earlyinfantileonsetepilepsy pages 1-2)

10. Diagnostics

Clinical evaluation

Suspect DEE89 in an infant with seizures beginning in the first months of life, severe developmental delay or stagnation, hypotonia/weakness, and an encephalopathic EEG—particularly with consanguinity or affected siblings. EEG documents seizure type and background severity but is not specific. Brain MRI evaluates structural causes and complications; a normal MRI does not exclude DEE89 because 4/6 reported scans were normal. Routine blood, urine, CSF, enzyme, or tissue biomarkers have not been validated. (neuray2020earlyinfantileonsetepilepsy pages 3-3)

Molecular confirmation

1. Use a comprehensive developmental-epilepsy panel including GAD1, trio exome sequencing, or trio genome sequencing.
2. Confirm candidate variants by an orthogonal method and establish trans phase through parental testing.
3. Evaluate sequence variants, exon-level deletions/duplications, splice variants, and—if WGS/RNA studies are available—deep intronic or regulatory defects.
4. Apply ACMG/AMP criteria using population rarity, predicted loss of function, segregation, phenotype concordance, and functional evidence.

WES was effective in the founding families. WGS can add CNV, structural, noncoding, and difficult-splice detection. CMA may be appropriate in unexplained developmental delay but will usually miss small GAD1 variants; karyotype and FISH have no disease-specific role. Mitochondrial and repeat-expansion tests are guided by the differential diagnosis, not DEE89 itself. No diagnostic RNA-seq, proteomic, metabolomic, epigenomic, or liquid-biopsy signature is validated.

Differential diagnosis

Important alternatives include other early-infantile DEEs—STXBP1, KCNQ2, SCN2A, SCN8A, CDKL5, KCNT1, DNM1, AP2M1, WWOX, PCDH12, and metabolic epilepsies such as ALDH7A1/PNPO-related vitamin-B6-dependent epilepsy. Structural brain disease, congenital infection, hypoxic injury, and inborn errors of metabolism should be assessed clinically. DEE89 is distinguished by confirmed biallelic GAD1 pathogenic variants; no electroclinical feature is pathognomonic.

Screening

DEE89 is not on routine newborn-screening panels, and no validated biochemical newborn marker exists. Targeted carrier, cascade, prenatal, or preimplantation testing is appropriate once familial variants are known.

11. Outcome and prognosis

No five- or ten-year survival, mortality rate, life expectancy, SUDEP incidence, or adult-outcome estimate exists. Gad1-null mouse neonatal lethality must not be extrapolated directly to humans with hypomorphic or partial-loss alleles.

Known morbidity is substantial: severe intellectual and communication disability occurred in all six original patients; weakness/hypotonia occurred in five; and half had drug-resistant epilepsy. Prognostic separation based on variant class is not yet possible. Seizure control does not guarantee cognitive recovery, because severe disability persisted in seizure-free patients. Potential complications follow from severe DEE generally—status epilepticus, aspiration, feeding difficulty, contractures/scoliosis, immobility, medication adverse effects, and SUDEP risk—but disease-specific rates are unknown. (neuray2020earlyinfantileonsetepilepsy pages 3-3, neuray2020earlyinfantileonsetepilepsy pages 6-6)

12. Treatment

Current management

There is no approved GAD1- or DEE89-specific therapy. Management should be multidisciplinary:

• Antiseizure medication: individualized by seizure type and EEG; 3/6 founding patients achieved pharmacological control and 3/6 were drug-resistant. Published evidence does not support one drug as uniquely effective. (neuray2020earlyinfantileonsetepilepsy pages 3-3)
• Rescue planning: emergency benzodiazepine plan and education regarding prolonged seizures/status epilepticus.
• Developmental care: early physical, occupational, speech/augmentative-communication, and feeding therapies.
• Orthopedic and nutritional care: surveillance for scoliosis, contractures, aspiration, poor growth, and need for adaptive equipment.
• Safety: seizure precautions and counseling regarding SUDEP.

Possible NCIt mappings include Anticonvulsant Agent (C264), Physical Therapy (C15308), Occupational Therapy (C15310), Speech Therapy (C15312), Genetic Counseling (C15246), and Palliative/Supportive Care (C15292); exact NCIt codes should be verified against the current release before database import.

Precision and experimental therapies

No DEE89-specific gene replacement, CRISPR editing, ASO, mRNA, cell therapy, or targeted small-molecule program has entered clinical trials, and the retrieved ClinicalTrials.gov search found no relevant interventional study. Increasing GAD1 expression, replacing GAD67, stabilizing residual enzyme, or augmenting GABAergic signaling are conceptual strategies, but chronic nonspecific GABA enhancement can cause sedation and may not restore early developmental signaling. Pyridoxine or PLP should not be represented as evidence-based DEE89 therapy absent biochemical deficiency or a supervised diagnostic trial for vitamin-B6-dependent epilepsy.

No pharmacogenomic response marker, response rate beyond the six-person series, treatment algorithm, or controlled adverse-event dataset exists.

13. Prevention

• Primary prevention: the sporadic occurrence of recessive alleles cannot be prevented by lifestyle or vaccination. Reproductive carrier testing, preimplantation genetic testing, chorionic-villus sampling, or amniocentesis can prevent or identify recurrence in families with known variants.
• Secondary prevention: no population screening program exists. Rapid genomic testing in early infantile DEE can shorten the diagnostic odyssey and support early seizure treatment and developmental intervention.
• Tertiary prevention: optimize seizure control, rescue therapy, vaccination and infection management, nutrition, aspiration precautions, mobility, bone health, communication support, and orthopedic surveillance.
• Counseling: offer parental testing, recurrence-risk counseling, cascade testing of adult relatives, and discussion of reproductive options.

There is no vaccine, environmental remediation, behavioral prophylaxis, or preventive medication specific to DEE89.

14. Other species and natural disease

No naturally occurring veterinary GAD1-associated syndrome equivalent to human DEE89 was identified, and there is no infectious transmission or zoonotic potential. Orthologs are evolutionarily conserved in vertebrates, including mouse Gad1 and zebrafish gad1b, reflecting conservation of GABA synthesis. Natural breed associations and Vertebrate Breed Ontology annotations are unavailable.

15. Model organisms

Mouse

Constitutive Gad1-null mice develop severe cleft palate and die neonatally. This strongly supports GAD1’s developmental and craniofacial roles but prevents characterization of postnatal seizures, cognition, and long-term disease progression. More generally, disruption of GAD enzymes or GABA-A receptor components can produce spontaneous seizures, supporting the proposed inhibitory-network mechanism. (neuray2020earlyinfantileonsetepilepsy pages 6-7, neuray2020earlyinfantileonsetepilepsy pages 1-1)

Suggested taxonomy is Mus musculus, NCBI Taxon 10090. Useful future models would include conditional interneuron-specific knockouts, hypomorphic or patient-variant knock-ins, and temporally controlled alleles that survive beyond birth.

Other model systems

No DEE89-specific zebrafish, Drosophila, C. elegans, patient-iPSC, neuronal culture, cerebral organoid, or humanized model was identified in the retrieved literature. These represent high-priority gaps. Patient-variant knock-in neurons could quantify GABA production, firing, synaptic inhibition, and rescue by gene replacement or residual-function modulators.

Current expert assessment and knowledge-base recommendations

DEE89 has a compelling gene–disease relationship because multiple unrelated families carried biallelic ultrarare damaging GAD1 variants, the phenotype matches loss of inhibitory neurotransmission, and the mouse knockout supports developmental consequences. Nevertheless, clinical validity is much stronger than clinical actionability: diagnosis can be made molecularly, but prognosis and treatment remain based on six cases and general DEE practice. The most defensible knowledge-base entry should therefore preserve exact denominators, label mechanistic assignments as human-genetic plus model-supported, and mark epidemiology, QoL, long-term survival, biomarkers, genotype–phenotype correlation, and precision treatment as unknown. (OpenTargets Search: developmental and epileptic encephalopathy 89-GAD1, neuray2020earlyinfantileonsetepilepsy pages 6-6, neuray2020earlyinfantileonsetepilepsy pages 1-1)

Principal reference: Neuray C, Maroofian R, Scala M, et al. Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants. Brain. Published online 10 July 2020;143(8):2388–2397. PMID: 32282878. DOI: https://doi.org/10.1093/brain/awaa178. (neuray2020earlyinfantileonsetepilepsy pages 3-3, neuray2020earlyinfantileonsetepilepsy pages 1-1)

References

1. (neuray2020earlyinfantileonsetepilepsy pages 3-3): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

2. (neuray2020earlyinfantileonsetepilepsy pages 1-1): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

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4. (neuray2020earlyinfantileonsetepilepsy pages 1-2): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

5. (neuray2020earlyinfantileonsetepilepsy pages 6-6): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

6. (neuray2020earlyinfantileonsetepilepsy pages 5-6): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

7. (neuray2020earlyinfantileonsetepilepsy pages 6-7): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

8. (neuray2020earlyinfantileonsetepilepsy pages 4-5): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

9. (neuray2020earlyinfantileonsetepilepsy pages 8-9): Caroline Neuray, Reza Maroofian, Marcello Scala, Tipu Sultan, Gurpur S Pai, Majid Mojarrad, Heba El Khashab, Leigh deHoll, Wyatt Yue, Hessa S Alsaif, Maria N Zanetti, Oscar Bello, Richard Person, Atieh Eslahi, Zaynab Khazaei, Masoumeh H Feizabadi, Stephanie Efthymiou, Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa, Hala T El-Bassyouni, Doaa R Soliman, Selahattin Tekes, Leyla Ozer, Volkan Baltaci, Suliman Khan, Christian Beetz, Khalda S Amr, Vincenzo Salpietro, Yalda Jamshidi, Fowzan S Alkuraya, and Henry Houlden. Early-infantile onset epilepsy and developmental delay caused by bi-allelic gad1 variants. Brain, 143:2388-2397, Jul 2020. URL: https://doi.org/10.1093/brain/awaa178, doi:10.1093/brain/awaa178. This article has 56 citations and is from a highest quality peer-reviewed journal.

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