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Intellectual disability-epilepsy-extrapyramidal syndrome(NEDHELS)

MedGen UID:
934650
Concept ID:
C4310683
Disease or Syndrome
Synonyms: Dyskinesia, seizures, and intellectual developmental disorder; NEDHELS
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): DEAF1 (11p15.5)
 
Monarch Initiative: MONDO:0014952
OMIM®: 617171
Orphanet: ORPHA468620

Definition

Neurodevelopmental disorder with hypotonia and impaired expressive language and with or without seizures (NEDHELS) is an autosomal recessive disorder characterized by hypotonia, poor feeding, and global developmental delay apparent from infancy. Most patients have poor overall growth, poor eye contact, sleep disturbances, and severely impaired expressive language. Affected individuals also tend to have behavioral problems, microcephaly, and variable dysmorphic features; many develop seizures. Brain imaging may show enlarged ventricles, thin corpus callosum and brainstem, and white matter abnormalities. The phenotype is variable (summary by Nabais Sa et al., 2019). [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).
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Involuntary movements
MedGen UID:
140884
Concept ID:
C0427086
Sign or Symptom
Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face.
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.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
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.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.

Professional guidelines

PubMed

Knight JS, Branch DW, Ortel TL
BMJ 2023 Feb 27;380:e069717. doi: 10.1136/bmj-2021-069717. PMID: 36849186
Salcedo-Arellano MJ, Hagerman RJ, Martínez-Cerdeño V
Gac Med Mex 2020;156(1):60-66. doi: 10.24875/GMM.19005275. PMID: 32026885
Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J
Circulation 2019 Jun 18;139(25):e1082-e1143. Epub 2018 Nov 10 doi: 10.1161/CIR.0000000000000625. PMID: 30586774Free PMC Article

Recent clinical studies

Etiology

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Diagnosis

Aref-Eshghi E, Kerkhof J, Pedro VP; Groupe DI France, Barat-Houari M, Ruiz-Pallares N, Andrau JC, Lacombe D, Van-Gils J, Fergelot P, Dubourg C, Cormier-Daire V, Rondeau S, Lecoquierre F, Saugier-Veber P, Nicolas G, Lesca G, Chatron N, Sanlaville D, Vitobello A, Faivre L, Thauvin-Robinet C, Laumonnier F, Raynaud M, Alders M, Mannens M, Henneman P, Hennekam RC, Velasco G, Francastel C, Ulveling D, Ciolfi A, Pizzi S, Tartaglia M, Heide S, Héron D, Mignot C, Keren B, Whalen S, Afenjar A, Bienvenu T, Campeau PM, Rousseau J, Levy MA, Brick L, Kozenko M, Balci TB, Siu VM, Stuart A, Kadour M, Masters J, Takano K, Kleefstra T, de Leeuw N, Field M, Shaw M, Gecz J, Ainsworth PJ, Lin H, Rodenhiser DI, Friez MJ, Tedder M, Lee JA, DuPont BR, Stevenson RE, Skinner SA, Schwartz CE, Genevieve D, Sadikovic B
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Yates TM, Drucker M, Barnicoat A, Low K, Gerkes EH, Fry AE, Parker MJ, O'Driscoll M, Charles P, Cox H, Marey I, Keren B, Rinne T, McEntagart M, Ramachandran V, Drury S, Vansenne F, Sival DA, Herkert JC, Callewaert B, Tan WH, Balasubramanian M
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Therapy

Liu SH, Saldanha IJ, Abraham AG, Rittiphairoj T, Hauswirth S, Gregory D, Ifantides C, Li T
Cochrane Database Syst Rev 2022 Oct 21;10(10):CD015070. doi: 10.1002/14651858.CD015070.pub2. PMID: 36269562Free PMC Article
Bruno LP, Doddato G, Valentino F, Baldassarri M, Tita R, Fallerini C, Bruttini M, Lo Rizzo C, Mencarelli MA, Mari F, Pinto AM, Fava F, Fabbiani A, Lamacchia V, Carrer A, Caputo V, Granata S, Benetti E, Zguro K, Furini S, Renieri A, Ariani F
Int J Mol Sci 2021 Dec 14;22(24) doi: 10.3390/ijms222413439. PMID: 34948243Free PMC Article
Montouris G, Aboumatar S, Burdette D, Kothare S, Kuzniecky R, Rosenfeld W, Chung S
Epilepsy Behav 2020 Sep;110:107146. Epub 2020 Jun 18 doi: 10.1016/j.yebeh.2020.107146. PMID: 32563898
Samanta D
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Prognosis

Yates TM, Drucker M, Barnicoat A, Low K, Gerkes EH, Fry AE, Parker MJ, O'Driscoll M, Charles P, Cox H, Marey I, Keren B, Rinne T, McEntagart M, Ramachandran V, Drury S, Vansenne F, Sival DA, Herkert JC, Callewaert B, Tan WH, Balasubramanian M
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Am J Hum Genet 2019 Mar 7;104(3):530-541. Epub 2019 Feb 28 doi: 10.1016/j.ajhg.2019.01.010. PMID: 30827496Free PMC Article
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Renier D, Lajeunie E, Arnaud E, Marchac D
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Clinical prediction guides

Dingemans AJM, Truijen KMG, Kim JH, Alaçam Z, Faivre L, Collins KM, Gerkes EH, van Haelst M, van de Laar IMBH, Lindstrom K, Nizon M, Pauling J, Heropolitańska-Pliszka E, Plomp AS, Racine C, Sachdev R, Sinnema M, Skranes J, Veenstra-Knol HE, Verberne EA, Vulto-van Silfhout AT, Wilsterman MEF, Ahn EE, de Vries BBA, Vissers LELM
Eur J Hum Genet 2022 Mar;30(3):271-281. Epub 2021 Sep 15 doi: 10.1038/s41431-021-00960-4. PMID: 34521999Free PMC Article
Sanchez-Jimeno C, Blanco-Kelly F, López-Grondona F, Losada-Del Pozo R, Moreno B, Rodrigo-Moreno M, Martinez-Cayuelas E, Riveiro-Alvarez R, Fenollar-Cortés M, Ayuso C, Rodríguez de Alba M, Lorda-Sanchez I, Almoguera B
Genes (Basel) 2021 Aug 30;12(9) doi: 10.3390/genes12091360. PMID: 34573342Free PMC Article
Inuzuka LM, Macedo-Souza LI, Della-Rippa B, Monteiro FP, Delgado DS, Godoy LF, Ramos L, de Athayde Costa LS, Garzon E, Kok F
Epileptic Disord 2020 Jun 1;22(3):317-322. doi: 10.1684/epd.2020.1166. PMID: 32597767
Yates TM, Drucker M, Barnicoat A, Low K, Gerkes EH, Fry AE, Parker MJ, O'Driscoll M, Charles P, Cox H, Marey I, Keren B, Rinne T, McEntagart M, Ramachandran V, Drury S, Vansenne F, Sival DA, Herkert JC, Callewaert B, Tan WH, Balasubramanian M
Hum Mutat 2020 May;41(5):1042-1050. Epub 2020 Mar 5 doi: 10.1002/humu.24001. PMID: 32097528
Moortgat S, Berland S, Aukrust I, Maystadt I, Baker L, Benoit V, Caro-Llopis A, Cooper NS, Debray FG, Faivre L, Gardeitchik T, Haukanes BI, Houge G, Kivuva E, Martinez F, Mehta SG, Nassogne MC, Powell-Hamilton N, Pfundt R, Rosello M, Prescott T, Vasudevan P, van Loon B, Verellen-Dumoulin C, Verloes A, Lippe CV, Wakeling E, Wilkie AOM, Wilson L, Yuen A, Study D, Low KJ, Newbury-Ecob RA
Eur J Hum Genet 2018 Jan;26(1):64-74. Epub 2017 Nov 27 doi: 10.1038/s41431-017-0038-6. PMID: 29180823Free PMC Article

Recent systematic reviews

Paprocka J, Kaminiów K, Yetkin O, Tekturk P, Baykan B, Leiz S, Kluger G, Striano P
Seizure 2024 Mar;116:14-23. Epub 2022 Dec 8 doi: 10.1016/j.seizure.2022.12.001. PMID: 36526544
Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I, Davies MJ, Ernstoff MS, Fecher L, Funchain P, Jaiyesimi I, Mammen JS, Naidoo J, Naing A, Phillips T, Porter LD, Reichner CA, Seigel C, Song JM, Spira A, Suarez-Almazor M, Swami U, Thompson JA, Vikas P, Wang Y, Weber JS, Bollin K, Ghosh M
J Clin Oncol 2021 Dec 10;39(35):3978-3992. Epub 2021 Nov 1 doi: 10.1200/JCO.21.01992. PMID: 34724386
Ruiz-González L, Lucena-Antón D, Salazar A, Martín-Valero R, Moral-Munoz JA
J Intellect Disabil Res 2019 Aug;63(8):1041-1067. Epub 2019 Feb 20 doi: 10.1111/jir.12606. PMID: 30788876
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Circulation 2019 Jun 18;139(25):e1082-e1143. Epub 2018 Nov 10 doi: 10.1161/CIR.0000000000000625. PMID: 30586774Free PMC Article
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