U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

NEDSGA is an autosomal dominant disorder characterized by global developmental delay apparent from infancy or early childhood, resulting in variable intellectual disability 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 characterised 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.
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.
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\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\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.
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 condition of being easily bothered or annoyed.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
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.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
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.
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

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
Colvin MK, Stern TA
J Clin Psychiatry 2015 Sep;76(9):e1148. doi: 10.4088/JCP.12040vr1c. PMID: 26455686

Recent clinical studies

Etiology

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
McPartland J, Volkmar FR
Handb Clin Neurol 2012;106:407-18. doi: 10.1016/B978-0-444-52002-9.00023-1. PMID: 22608634Free PMC Article

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
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
Doernberg E, Hollander E
CNS Spectr 2016 Aug;21(4):295-9. Epub 2016 Jul 1 doi: 10.1017/S1092852916000262. PMID: 27364515
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

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
Li M, Francis E, Hinkle SN, Ajjarapu AS, Zhang C
Nutrients 2019 Jul 17;11(7) doi: 10.3390/nu11071628. PMID: 31319515Free 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
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
Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK
Cell 2013 Dec 19;155(7):1451-63. Epub 2013 Dec 5 doi: 10.1016/j.cell.2013.11.024. PMID: 24315484Free 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
Kalenik A, Kardaś K, Rahnama A, Sirojć K, Wolańczyk T
Prog Neuropsychopharmacol Biol Psychiatry 2021 Aug 30;110:110277. Epub 2021 Feb 6 doi: 10.1016/j.pnpbp.2021.110277. PMID: 33561522
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
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
Magnin E, Maurs C
Rev Neurol (Paris) 2017 Jul-Aug;173(7-8):506-515. Epub 2017 Aug 26 doi: 10.1016/j.neurol.2017.07.008. PMID: 28844700
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
Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P
J Psychopharmacol 2015 Jul;29(7):753-63. Epub 2015 Jun 3 doi: 10.1177/0269881115587958. PMID: 26040902
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

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...