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Neurodevelopmental disorder with or without seizures and gait abnormalities(NEDSGA)

MedGen UID:
1645968
Concept ID:
C4693391
Disease or Syndrome
Synonyms: NEDSGA; NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT SEIZURES AND GAIT ABNORMALITIES
 
Gene (location): GRIA4 (11q22.3)
 
Monarch Initiative: MONDO:0060641
OMIM®: 617864

Definition

Neurodevelopmental disorder with or without seizures and gait abnormalities (NEDSGA) is an autosomal dominant disorder characterized by global developmental delay apparent from infancy or early childhood, resulting in variably impaired intellectual development that can range from profound with absent speech to mild with an ability to attend special schools. Most affected individuals show irritability, stiffness, and hypertonia early in life, which progresses to spasticity and impaired gait later. Some patients may develop seizures of variable severity early in life (summary by Martin et al., 2017). [from OMIM]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
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.
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).
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
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.
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.
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.
Short attention span
MedGen UID:
82652
Concept ID:
C0262630
Finding
Reduced attention span characterized by distractibility and impulsivity.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
Spastic paralysis affecting all four limbs.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
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.
EEG with generalized slow activity
MedGen UID:
866862
Concept ID:
C4021217
Finding
Diffuse slowing of cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Joint contracture
MedGen UID:
3228
Concept ID:
C0009918
Anatomical Abnormality
A limitation in the passive range of motion of a joint resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
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.
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.

Professional guidelines

PubMed

Rogers JP, Oldham MA, Fricchione G, Northoff G, Ellen Wilson J, Mann SC, Francis A, Wieck A, Elizabeth Wachtel L, Lewis G, Grover S, Hirjak D, Ahuja N, Zandi MS, Young AH, Fone K, Andrews S, Kessler D, Saifee T, Gee S, Baldwin DS, David AS
J Psychopharmacol 2023 Apr;37(4):327-369. Epub 2023 Apr 11 doi: 10.1177/02698811231158232. PMID: 37039129Free PMC Article
Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, Newcorn JH, Gignac M, Al Saud NM, Manor I, Rohde LA, Yang L, Cortese S, Almagor D, Stein MA, Albatti TH, Aljoudi HF, Alqahtani MMJ, Asherson P, Atwoli L, Bölte S, Buitelaar JK, Crunelle CL, Daley D, Dalsgaard S, Döpfner M, Espinet S, Fitzgerald M, Franke B, Gerlach M, Haavik J, Hartman CA, Hartung CM, Hinshaw SP, Hoekstra PJ, Hollis C, Kollins SH, Sandra Kooij JJ, Kuntsi J, Larsson H, Li T, Liu J, Merzon E, Mattingly G, Mattos P, McCarthy S, Mikami AY, Molina BSG, Nigg JT, Purper-Ouakil D, Omigbodun OO, Polanczyk GV, Pollak Y, Poulton AS, Rajkumar RP, Reding A, Reif A, Rubia K, Rucklidge J, Romanos M, Ramos-Quiroga JA, Schellekens A, Scheres A, Schoeman R, Schweitzer JB, Shah H, Solanto MV, Sonuga-Barke E, Soutullo C, Steinhausen HC, Swanson JM, Thapar A, Tripp G, van de Glind G, van den Brink W, Van der Oord S, Venter A, Vitiello B, Walitza S, Wang Y
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

Recent clinical studies

Etiology

Doi M, Usui N, Shimada S
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Pediatr Clin North Am 2019 Apr;66(2):509-523. Epub 2019 Feb 1 doi: 10.1016/j.pcl.2018.12.015. PMID: 30819351
Ito S
Clin Pharmacol Ther 2018 Oct;104(4):592-594. doi: 10.1002/cpt.1182. PMID: 30222188
Thapar A, Cooper M
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Diagnosis

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
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Pediatr Clin North Am 2019 Apr;66(2):509-523. Epub 2019 Feb 1 doi: 10.1016/j.pcl.2018.12.015. PMID: 30819351
Thibaut F
Dialogues Clin Neurosci 2018 Dec;20(4):251-252. doi: 10.31887/DCNS.2018.20.4/fthibaut. PMID: 30936765Free PMC Article
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Therapy

Armstrong C, Marsh ED
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Encephale 2020 Feb;46(1):30-40. Epub 2019 Oct 11 doi: 10.1016/j.encep.2019.06.005. PMID: 31610922
Ito S
Clin Pharmacol Ther 2018 Oct;104(4):592-594. doi: 10.1002/cpt.1182. PMID: 30222188
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

Prognosis

Ahrens AP, Hyötyläinen T, Petrone JR, Igelström K, George CD, Garrett TJ, Orešič M, Triplett EW, Ludvigsson J
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Rund BR
Scand J Psychol 2018 Feb;59(1):49-58. doi: 10.1111/sjop.12414. PMID: 29356007
Kałużna-Czaplińska J, Żurawicz E, Jóźwik-Pruska J
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Krol A, Feng G
Curr Opin Neurobiol 2018 Feb;48:59-63. Epub 2017 Nov 7 doi: 10.1016/j.conb.2017.10.014. PMID: 29125977
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

Clinical prediction guides

Ahrens AP, Hyötyläinen T, Petrone JR, Igelström K, George CD, Garrett TJ, Orešič M, Triplett EW, Ludvigsson J
Cell 2024 Apr 11;187(8):1853-1873.e15. Epub 2024 Apr 3 doi: 10.1016/j.cell.2024.02.035. PMID: 38574728
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
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
Rund BR
Scand J Psychol 2018 Feb;59(1):49-58. doi: 10.1111/sjop.12414. PMID: 29356007
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

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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

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