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Neurodevelopmental disorder with or without early-onset generalized epilepsy(NEDEGE)

MedGen UID:
1737097
Concept ID:
C5436914
Disease or Syndrome
Synonyms: NEDEGE; NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT EARLY-ONSET GENERALIZED EPILEPSY
 
Gene (location): NBEA (13q13.3)
 
Monarch Initiative: MONDO:0030930
OMIM®: 619157

Definition

Neurodevelopmental disorder with or without early-onset generalized epilepsy (NEDEGE) is characterized by global developmental delay apparent from infancy or early childhood. Affected individuals have variably impaired intellectual development, speech delay, and behavioral abnormalities. About half of patients develop early-onset generalized epilepsy with different seizure types; myoclonic seizures and myoclonic-atonic epilepsy are commonly observed. The seizures may remit with age or remain refractory to treatment. Brain imaging is essentially normal and there are no significant accompanying neurologic or systemic abnormalities (summary by Mulhern et al., 2018). [from OMIM]

Clinical features

From HPO
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Interictal epileptiform activity
MedGen UID:
869073
Concept ID:
C4023491
Finding
Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterised by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterised by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.

Professional guidelines

PubMed

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Neurosci Biobehav Rev 2021 Sep;128:789-818. Epub 2021 Feb 4 doi: 10.1016/j.neubiorev.2021.01.022. PMID: 33549739Free PMC Article
Wolraich ML, Hagan JF Jr, Allan C, Chan E, Davison D, Earls M, Evans SW, Flinn SK, Froehlich T, Frost J, Holbrook JR, Lehmann CU, Lessin HR, Okechukwu K, Pierce KL, Winner JD, Zurhellen W; SUBCOMMITTEE ON CHILDREN AND ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVE DISORDER
Pediatrics 2019 Oct;144(4) doi: 10.1542/peds.2019-2528. PMID: 31570648Free PMC Article
Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH
Am J Hum Genet 2010 May 14;86(5):749-64. doi: 10.1016/j.ajhg.2010.04.006. PMID: 20466091Free PMC Article

Recent clinical studies

Etiology

Bölte S, Neufeld J, Marschik PB, Williams ZJ, Gallagher L, Lai MC
Nat Rev Neurol 2023 Mar;19(3):136-159. Epub 2023 Feb 6 doi: 10.1038/s41582-023-00774-6. PMID: 36747038Free PMC Article
Han VX, Patel S, Jones HF, Dale RC
Nat Rev Neurol 2021 Sep;17(9):564-579. Epub 2021 Aug 2 doi: 10.1038/s41582-021-00530-8. PMID: 34341569
Turner TN, Wilfert AB, Bakken TE, Bernier RA, Pepper MR, Zhang Z, Torene RI, Retterer K, Eichler EE
Am J Hum Genet 2019 Dec 5;105(6):1274-1285. Epub 2019 Nov 27 doi: 10.1016/j.ajhg.2019.11.003. PMID: 31785789Free PMC Article
Cheng LH, Liu YW, Wu CC, Wang S, Tsai YC
J Food Drug Anal 2019 Jul;27(3):632-648. Epub 2019 Feb 10 doi: 10.1016/j.jfda.2019.01.002. PMID: 31324280Free PMC Article
Thapar A, Cooper M
Lancet 2016 Mar 19;387(10024):1240-50. Epub 2015 Sep 17 doi: 10.1016/S0140-6736(15)00238-X. PMID: 26386541

Diagnosis

Bölte S, Neufeld J, Marschik PB, Williams ZJ, Gallagher L, Lai MC
Nat Rev Neurol 2023 Mar;19(3):136-159. Epub 2023 Feb 6 doi: 10.1038/s41582-023-00774-6. PMID: 36747038Free PMC Article
Morris-Rosendahl DJ, Crocq MA
Dialogues Clin Neurosci 2020 Mar;22(1):65-72. doi: 10.31887/DCNS.2020.22.1/macrocq. PMID: 32699506Free PMC Article
May T, Adesina I, McGillivray J, Rinehart NJ
Curr Opin Neurol 2019 Aug;32(4):622-626. doi: 10.1097/WCO.0000000000000714. PMID: 31135460
Thapar A, Cooper M, Rutter M
Lancet Psychiatry 2017 Apr;4(4):339-346. Epub 2016 Dec 13 doi: 10.1016/S2215-0366(16)30376-5. PMID: 27979720
Stamberger H, Nikanorova M, Willemsen MH, Accorsi P, Angriman M, Baier H, Benkel-Herrenbrueck I, Benoit V, Budetta M, Caliebe A, Cantalupo G, Capovilla G, Casara G, Courage C, Deprez M, Destrée A, Dilena R, Erasmus CE, Fannemel M, Fjær R, Giordano L, Helbig KL, Heyne HO, Klepper J, Kluger GJ, Lederer D, Lodi M, Maier O, Merkenschlager A, Michelberger N, Minetti C, Muhle H, Phalin J, Ramsey K, Romeo A, Schallner J, Schanze I, Shinawi M, Sleegers K, Sterbova K, Syrbe S, Traverso M, Tzschach A, Uldall P, Van Coster R, Verhelst H, Viri M, Winter S, Wolff M, Zenker M, Zoccante L, De Jonghe P, Helbig I, Striano P, Lemke JR, Møller RS, Weckhuysen S
Neurology 2016 Mar 8;86(10):954-62. Epub 2016 Feb 10 doi: 10.1212/WNL.0000000000002457. PMID: 26865513

Therapy

Weibel S, Menard O, Ionita A, Boumendjel M, Cabelguen C, Kraemer C, Micoulaud-Franchi JA, Bioulac S, Perroud N, Sauvaget A, Carton L, Gachet M, Lopez R
Encephale 2020 Feb;46(1):30-40. Epub 2019 Oct 11 doi: 10.1016/j.encep.2019.06.005. PMID: 31610922
Esposito S, Laino D, D'Alonzo R, Mencarelli A, Di Genova L, Fattorusso A, Argentiero A, Mencaroni E
J Transl Med 2019 Mar 12;17(1):77. doi: 10.1186/s12967-019-1835-1. PMID: 30871585Free PMC Article
Shamir R
Nestle Nutr Inst Workshop Ser 2016;86:67-76. Epub 2016 Jun 23 doi: 10.1159/000442724. PMID: 27336781
Thapar A, Cooper M
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Margolis SS, Sell GL, Zbinden MA, Bird LM
Neurotherapeutics 2015 Jul;12(3):641-50. doi: 10.1007/s13311-015-0361-y. PMID: 26040994Free PMC Article

Prognosis

Robinson-Agramonte MLA, Noris García E, Fraga Guerra J, Vega Hurtado Y, Antonucci N, Semprún-Hernández N, Schultz S, Siniscalco D
Int J Mol Sci 2022 Mar 11;23(6) doi: 10.3390/ijms23063033. PMID: 35328471Free PMC Article
Thapar A, Cooper M
Lancet 2016 Mar 19;387(10024):1240-50. Epub 2015 Sep 17 doi: 10.1016/S0140-6736(15)00238-X. PMID: 26386541
Stoodley CJ
Cerebellum 2016 Feb;15(1):34-37. doi: 10.1007/s12311-015-0715-3. PMID: 26298473Free PMC Article
Baxter AJ, Brugha TS, Erskine HE, Scheurer RW, Vos T, Scott JG
Psychol Med 2015 Feb;45(3):601-13. Epub 2014 Aug 11 doi: 10.1017/S003329171400172X. PMID: 25108395
Kawicka A, Regulska-Ilow B
Rocz Panstw Zakl Hig 2013;64(1):1-12. PMID: 23789306

Clinical prediction guides

Morris-Rosendahl DJ, Crocq MA
Dialogues Clin Neurosci 2020 Mar;22(1):65-72. doi: 10.31887/DCNS.2020.22.1/macrocq. PMID: 32699506Free PMC Article
Lautarescu A, Craig MC, Glover V
Int Rev Neurobiol 2020;150:17-40. Epub 2019 Dec 14 doi: 10.1016/bs.irn.2019.11.002. PMID: 32204831
Turner TN, Wilfert AB, Bakken TE, Bernier RA, Pepper MR, Zhang Z, Torene RI, Retterer K, Eichler EE
Am J Hum Genet 2019 Dec 5;105(6):1274-1285. Epub 2019 Nov 27 doi: 10.1016/j.ajhg.2019.11.003. PMID: 31785789Free PMC Article
Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA
Epilepsia 2018 May;59(5):1062-1071. Epub 2018 Apr 14 doi: 10.1111/epi.14074. PMID: 29655203
Thapar A, Cooper M, Rutter M
Lancet Psychiatry 2017 Apr;4(4):339-346. Epub 2016 Dec 13 doi: 10.1016/S2215-0366(16)30376-5. PMID: 27979720

Recent systematic reviews

Siafis S, Çıray O, Wu H, Schneider-Thoma J, Bighelli I, Krause M, Rodolico A, Ceraso A, Deste G, Huhn M, Fraguas D, San José Cáceres A, Mavridis D, Charman T, Murphy DG, Parellada M, Arango C, Leucht S
Mol Autism 2022 Mar 4;13(1):10. doi: 10.1186/s13229-022-00488-4. PMID: 35246237Free PMC Article
Silva EAD Junior, Medeiros WMB, Torro N, Sousa JMM, Almeida IBCM, Costa FBD, Pontes KM, Nunes ELG, Rosa MDD, Albuquerque KLGD
Trends Psychiatry Psychother 2022 Jun 13;44:e20200149. doi: 10.47626/2237-6089-2020-0149. PMID: 34043900Free PMC Article
Sayal K, Prasad V, Daley D, Ford T, Coghill D
Lancet Psychiatry 2018 Feb;5(2):175-186. Epub 2017 Oct 9 doi: 10.1016/S2215-0366(17)30167-0. PMID: 29033005
Lucas BR, Elliott EJ, Coggan S, Pinto RZ, Jirikowic T, McCoy SW, Latimer J
BMC Pediatr 2016 Nov 29;16(1):193. doi: 10.1186/s12887-016-0731-6. PMID: 27899082Free PMC Article
Grandjean P, Landrigan PJ
Lancet Neurol 2014 Mar;13(3):330-8. Epub 2014 Feb 17 doi: 10.1016/S1474-4422(13)70278-3. PMID: 24556010Free PMC Article

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