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Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures(NEDLBAS)

MedGen UID:
1841001
Concept ID:
C5830365
Disease or Syndrome
Synonym: NEDLBAS
 
Gene (location): AGO1 (1p34.3)
 
Monarch Initiative: MONDO:0859531
OMIM®: 620292

Definition

Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (NEDLBAS), is characterized by global developmental delay with variably impaired intellectual development apparent from infancy or early childhood. Affected individuals have significant speech delay, and most demonstrate behavioral abnormalities, including autistic features. About half of patients develop seizures, which may be controlled or refractory. More variable features include hypotonia, feeding difficulties, and subtle facial dysmorphism (Schalk et al., 2022). [from OMIM]

Clinical features

From HPO
Mild short stature
MedGen UID:
461427
Concept ID:
C3150077
Finding
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
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).
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Febrile seizure (within the age range of 3 months to 6 years)
MedGen UID:
3232
Concept ID:
C0009952
Disease or Syndrome
A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years.
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Sign or Symptom
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.
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.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
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.
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\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\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.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Globus pallidus calcification
MedGen UID:
1642590
Concept ID:
C4703448
Disease or Syndrome
Pathological deposition of calcium salts in the globus pallidus.
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.
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Telecanthus
MedGen UID:
140836
Concept ID:
C0423113
Finding
Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Almond-shaped palpebral fissure
MedGen UID:
870336
Concept ID:
C4024780
Finding
A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Professional guidelines

PubMed

Charalambous M, Muñana K, Patterson EE, Platt SR, Volk HA
J Vet Intern Med 2024 Jan-Feb;38(1):19-40. Epub 2023 Nov 3 doi: 10.1111/jvim.16928. PMID: 37921621Free PMC Article
Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, Pressler R, Auvin S, Samia P, Hirsch E, Galicchio S, Triki C, Snead OC, Wiebe S, Cross JH, Tinuper P, Scheffer IE, Perucca E, Moshé SL, Nabbout R
Epilepsia 2022 Jun;63(6):1349-1397. Epub 2022 May 3 doi: 10.1111/epi.17239. PMID: 35503712
Abboud H, Probasco JC, Irani S, Ances B, Benavides DR, Bradshaw M, Christo PP, Dale RC, Fernandez-Fournier M, Flanagan EP, Gadoth A, George P, Grebenciucova E, Jammoul A, Lee ST, Li Y, Matiello M, Morse AM, Rae-Grant A, Rojas G, Rossman I, Schmitt S, Venkatesan A, Vernino S, Pittock SJ, Titulaer MJ; Autoimmune Encephalitis Alliance Clinicians Network
J Neurol Neurosurg Psychiatry 2021 Jul;92(7):757-768. Epub 2021 Mar 1 doi: 10.1136/jnnp-2020-325300. PMID: 33649022Free PMC Article

Recent clinical studies

Etiology

Wang X, Yang F, Chen B, Jiang W
Acta Neurol Scand 2022 Dec;146(6):752-760. Epub 2022 Oct 26 doi: 10.1111/ane.13718. PMID: 36285875
Ziobro J, Shellhaas RA
Semin Neurol 2020 Apr;40(2):246-256. Epub 2020 Mar 6 doi: 10.1055/s-0040-1702943. PMID: 32143234
Shellhaas RA
Handb Clin Neurol 2019;162:347-361. doi: 10.1016/B978-0-444-64029-1.00017-5. PMID: 31324320
Gavvala JR, Schuele SU
JAMA 2016 Dec 27;316(24):2657-2668. doi: 10.1001/jama.2016.18625. PMID: 28027373
Patterson JL, Carapetian SA, Hageman JR, Kelley KR
Pediatr Ann 2013 Dec;42(12):249-54. doi: 10.3928/00904481-20131122-09. PMID: 24295158

Diagnosis

Wirrell E
Continuum (Minneap Minn) 2022 Apr 1;28(2):230-260. doi: 10.1212/CON.0000000000001074. PMID: 35393959
Ziobro J, Shellhaas RA
Semin Neurol 2020 Apr;40(2):246-256. Epub 2020 Mar 6 doi: 10.1055/s-0040-1702943. PMID: 32143234
Shellhaas RA
Handb Clin Neurol 2019;162:347-361. doi: 10.1016/B978-0-444-64029-1.00017-5. PMID: 31324320
Patterson JL, Carapetian SA, Hageman JR, Kelley KR
Pediatr Ann 2013 Dec;42(12):249-54. doi: 10.3928/00904481-20131122-09. PMID: 24295158
Beghi E, Carpio A, Forsgren L, Hesdorffer DC, Malmgren K, Sander JW, Tomson T, Hauser WA
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Therapy

Rosenthal ES
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Prognosis

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Dev Med Child Neurol 2019 Jan;61(1):82-90. Epub 2018 Sep 7 doi: 10.1111/dmcn.14015. PMID: 30191957
Patterson JL, Carapetian SA, Hageman JR, Kelley KR
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Clinical prediction guides

Fu A, Lado FA
J Clin Neurophysiol 2024 Mar 1;41(3):207-213. doi: 10.1097/WNP.0000000000001045. PMID: 38436388
Cousin MA, Creighton BA, Breau KA, Spillmann RC, Torti E, Dontu S, Tripathi S, Ajit D, Edwards RJ, Afriyie S, Bay JC, Harper KM, Beltran AA, Munoz LJ, Falcon Rodriguez L, Stankewich MC, Person RE, Si Y, Normand EA, Blevins A, May AS, Bier L, Aggarwal V, Mancini GMS, van Slegtenhorst MA, Cremer K, Becker J, Engels H, Aretz S, MacKenzie JJ, Brilstra E, van Gassen KLI, van Jaarsveld RH, Oegema R, Parsons GM, Mark P, Helbig I, McKeown SE, Stratton R, Cogne B, Isidor B, Cacheiro P, Smedley D, Firth HV, Bierhals T, Kloth K, Weiss D, Fairley C, Shieh JT, Kritzer A, Jayakar P, Kurtz-Nelson E, Bernier RA, Wang T, Eichler EE, van de Laar IMBH, McConkie-Rosell A, McDonald MT, Kemppainen J, Lanpher BC, Schultz-Rogers LE, Gunderson LB, Pichurin PN, Yoon G, Zech M, Jech R, Winkelmann J; Undiagnosed Diseases Network; Genomics England Research Consortium, Beltran AS, Zimmermann MT, Temple B, Moy SS, Klee EW, Tan QK, Lorenzo DN
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Nat Commun 2019 Oct 15;10(1):4679. doi: 10.1038/s41467-019-12435-8. PMID: 31616000Free PMC Article
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Recent systematic reviews

Pressler RM, Abend NS, Auvin S, Boylan G, Brigo F, Cilio MR, De Vries LS, Elia M, Espeche A, Hahn CD, Inder T, Jette N, Kakooza-Mwesige A, Mader S, Mizrahi EM, Moshé SL, Nagarajan L, Noyman I, Nunes ML, Samia P, Shany E, Shellhaas RA, Subota A, Triki CC, Tsuchida T, Vinayan KP, Wilmshurst JM, Yozawitz EG, Hartmann H
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Epilepsia 2022 Mar;63(3):513-524. Epub 2022 Jan 3 doi: 10.1111/epi.17157. PMID: 34981509
Steinert T, Fröscher W
Pharmacopsychiatry 2018 Jul;51(4):121-135. Epub 2017 Aug 29 doi: 10.1055/s-0043-117962. PMID: 28850959
Mewasingh LD
BMJ Clin Evid 2014 Jan 31;2014 PMID: 24484859Free PMC Article
Beghi E, Carpio A, Forsgren L, Hesdorffer DC, Malmgren K, Sander JW, Tomson T, Hauser WA
Epilepsia 2010 Apr;51(4):671-5. Epub 2009 Sep 3 doi: 10.1111/j.1528-1167.2009.02285.x. PMID: 19732133

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