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Neurodevelopmental disorder with language impairment and behavioral abnormalities(NEDLIB)

MedGen UID:
1708389
Concept ID:
C5394502
Disease or Syndrome
Synonym: GRIA2-related neurodevelopmental disorder
 
Gene (location): GRIA2 (4q32.1)
 
Monarch Initiative: MONDO:0030060
OMIM®: 618917

Definition

Neurodevelopmental disorder with speech impairment and behavioral abnormalities (NEDLIB) is characterized by impaired intellectual development or developmental delay, behavioral abnormalities including autistic features, and language impairment. Other features include seizures and developmental regression (Salpietro et al., 2019). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
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.
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.
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.
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.
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.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Clonic seizure
MedGen UID:
66708
Concept ID:
C0234535
Disease or Syndrome
A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Tonic seizure
MedGen UID:
82855
Concept ID:
C0270844
Disease or Syndrome
A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Stereotypical hand wringing
MedGen UID:
646835
Concept ID:
C0562479
Finding
Habitual clasping and wringing of the hands in the middle of the body, similar to a hand-washing movement.
Compulsive behaviors
MedGen UID:
109373
Concept ID:
C0600104
Mental or Behavioral Dysfunction
Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
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.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
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.
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.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Anatomical Abnormality
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.

Professional guidelines

PubMed

D'Onofrio G, Accogli A, Severino M, Caliskan H, Kokotović T, Blazekovic A, Jercic KG, Markovic S, Zigman T, Goran K, Barišić N, Duranovic V, Ban A, Borovecki F, Ramadža DP, Barić I, Fazeli W, Herkenrath P, Marini C, Vittorini R, Gowda V, Bouman A, Rocca C, Alkhawaja IA, Murtaza BN, Rehman MMU, Al Alam C, Nader G, Mancardi MM, Giacomini T, Srivastava S, Alvi JR, Tomoum H, Matricardi S, Iacomino M, Riva A, Scala M, Madia F, Pistorio A, Salpietro V, Minetti C, Rivière JB, Srour M, Efthymiou S, Maroofian R, Houlden H, Vernes SC, Zara F, Striano P, Nagy V
Hum Genet 2023 Jul;142(7):909-925. Epub 2023 May 14 doi: 10.1007/s00439-023-02552-2. PMID: 37183190Free PMC Article
Sabus A, Feinstein J, Romani P, Goldson E, Blackmer A
Pharmacotherapy 2019 Jun;39(6):645-664. Epub 2019 Mar 27 doi: 10.1002/phar.2238. PMID: 30793794Free PMC Article
Gładysz D, Krzywdzińska A, Hozyasz KK
Mol Neurobiol 2018 Aug;55(8):6387-6435. Epub 2018 Jan 6 doi: 10.1007/s12035-017-0822-x. PMID: 29307081Free PMC Article

Recent clinical studies

Etiology

Bar C, Barcia G, Jennesson M, Le Guyader G, Schneider A, Mignot C, Lesca G, Breuillard D, Montomoli M, Keren B, Doummar D, Billette de Villemeur T, Afenjar A, Marey I, Gerard M, Isnard H, Poisson A, Dupont S, Berquin P, Meyer P, Genevieve D, De Saint Martin A, El Chehadeh S, Chelly J, Guët A, Scalais E, Dorison N, Myers CT, Mefford HC, Howell KB, Marini C, Freeman JL, Nica A, Terrone G, Sekhara T, Lebre AS, Odent S, Sadleir LG, Munnich A, Guerrini R, Scheffer IE, Kabashi E, Nabbout R
Hum Mutat 2020 Jan;41(1):69-80. Epub 2019 Oct 4 doi: 10.1002/humu.23915. PMID: 31513310
Sabus A, Feinstein J, Romani P, Goldson E, Blackmer A
Pharmacotherapy 2019 Jun;39(6):645-664. Epub 2019 Mar 27 doi: 10.1002/phar.2238. PMID: 30793794Free PMC Article
Reichow B, Hume K, Barton EE, Boyd BA
Cochrane Database Syst Rev 2018 May 9;5(5):CD009260. doi: 10.1002/14651858.CD009260.pub3. PMID: 29742275Free PMC Article
Adams SA, Nasrallah HA
Schizophr Res 2018 May;195:3-12. Epub 2017 Jul 27 doi: 10.1016/j.schres.2017.07.018. PMID: 28755877
Muhle R, Trentacoste SV, Rapin I
Pediatrics 2004 May;113(5):e472-86. doi: 10.1542/peds.113.5.e472. PMID: 15121991

Diagnosis

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
Nat Genet 2021 Jul;53(7):1006-1021. Epub 2021 Jul 1 doi: 10.1038/s41588-021-00886-z. PMID: 34211179Free PMC Article
Bar C, Barcia G, Jennesson M, Le Guyader G, Schneider A, Mignot C, Lesca G, Breuillard D, Montomoli M, Keren B, Doummar D, Billette de Villemeur T, Afenjar A, Marey I, Gerard M, Isnard H, Poisson A, Dupont S, Berquin P, Meyer P, Genevieve D, De Saint Martin A, El Chehadeh S, Chelly J, Guët A, Scalais E, Dorison N, Myers CT, Mefford HC, Howell KB, Marini C, Freeman JL, Nica A, Terrone G, Sekhara T, Lebre AS, Odent S, Sadleir LG, Munnich A, Guerrini R, Scheffer IE, Kabashi E, Nabbout R
Hum Mutat 2020 Jan;41(1):69-80. Epub 2019 Oct 4 doi: 10.1002/humu.23915. PMID: 31513310
Sappok T, Diefenbacher A, Winterholler M
Dtsch Arztebl Int 2019 Nov 29;116(48):809-816. doi: 10.3238/arztebl.2019.0809. PMID: 31888794Free PMC Article
Butler MG
J Intellect Disabil Res 2017 Jun;61(6):568-579. Epub 2017 Apr 7 doi: 10.1111/jir.12382. PMID: 28387067Free PMC Article
Muhle R, Trentacoste SV, Rapin I
Pediatrics 2004 May;113(5):e472-86. doi: 10.1542/peds.113.5.e472. PMID: 15121991

Therapy

Homøe P, Heidemann CH, Damoiseaux RA, Lailach S, Lieu JEC, Phillips JS, Venekamp RP
Int J Pediatr Otorhinolaryngol 2020 Mar;130 Suppl 1(Suppl 1):109837. Epub 2019 Dec 20 doi: 10.1016/j.ijporl.2019.109837. PMID: 31883704Free PMC Article
Sabus A, Feinstein J, Romani P, Goldson E, Blackmer A
Pharmacotherapy 2019 Jun;39(6):645-664. Epub 2019 Mar 27 doi: 10.1002/phar.2238. PMID: 30793794Free PMC Article
Reichow B, Hume K, Barton EE, Boyd BA
Cochrane Database Syst Rev 2018 May 9;5(5):CD009260. doi: 10.1002/14651858.CD009260.pub3. PMID: 29742275Free PMC Article
Earl RK, Turner TN, Mefford HC, Hudac CM, Gerdts J, Eichler EE, Bernier RA
Mol Autism 2017;8:54. Epub 2017 Oct 5 doi: 10.1186/s13229-017-0173-5. PMID: 29034068Free PMC Article
Maber-Aleksandrowicz S, Avent C, Hassiotis A
Res Dev Disabil 2016 Feb-Mar;49-50:322-38. Epub 2016 Jan 7 doi: 10.1016/j.ridd.2015.12.005. PMID: 26773215

Prognosis

Santegoeds E, van der Schoot E, Roording-Ragetlie S, Klip H, Rommelse N
J Intellect Disabil Res 2022 Jan;66(1-2):162-177. Epub 2021 Aug 11 doi: 10.1111/jir.12874. PMID: 34378826Free PMC Article
Edemann-Callesen H, Winter C, Hadar R
Brain Stimul 2021 May-Jun;14(3):643-651. Epub 2021 Apr 2 doi: 10.1016/j.brs.2021.03.018. PMID: 33819680
Hermann BP, Struck AF, Stafstrom CE, Hsu DA, Dabbs K, Gundlach C, Almane D, Seidenberg M, Jones JE
Epilepsia 2020 Jul;61(7):1427-1437. Epub 2020 Jun 18 doi: 10.1111/epi.16569. PMID: 32557544Free PMC Article
Bar C, Barcia G, Jennesson M, Le Guyader G, Schneider A, Mignot C, Lesca G, Breuillard D, Montomoli M, Keren B, Doummar D, Billette de Villemeur T, Afenjar A, Marey I, Gerard M, Isnard H, Poisson A, Dupont S, Berquin P, Meyer P, Genevieve D, De Saint Martin A, El Chehadeh S, Chelly J, Guët A, Scalais E, Dorison N, Myers CT, Mefford HC, Howell KB, Marini C, Freeman JL, Nica A, Terrone G, Sekhara T, Lebre AS, Odent S, Sadleir LG, Munnich A, Guerrini R, Scheffer IE, Kabashi E, Nabbout R
Hum Mutat 2020 Jan;41(1):69-80. Epub 2019 Oct 4 doi: 10.1002/humu.23915. PMID: 31513310
Swillen A, McDonald-McGinn D
Am J Med Genet C Semin Med Genet 2015 Jun;169(2):172-81. Epub 2015 May 18 doi: 10.1002/ajmg.c.31435. PMID: 25989227Free PMC Article

Clinical prediction guides

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
Nat Genet 2021 Jul;53(7):1006-1021. Epub 2021 Jul 1 doi: 10.1038/s41588-021-00886-z. PMID: 34211179Free PMC Article
Hermann BP, Struck AF, Stafstrom CE, Hsu DA, Dabbs K, Gundlach C, Almane D, Seidenberg M, Jones JE
Epilepsia 2020 Jul;61(7):1427-1437. Epub 2020 Jun 18 doi: 10.1111/epi.16569. PMID: 32557544Free PMC Article
Guo H, Bettella E, Marcogliese PC, Zhao R, Andrews JC, Nowakowski TJ, Gillentine MA, Hoekzema K, Wang T, Wu H, Jangam S, Liu C, Ni H, Willemsen MH, van Bon BW, Rinne T, Stevens SJC, Kleefstra T, Brunner HG, Yntema HG, Long M, Zhao W, Hu Z, Colson C, Richard N, Schwartz CE, Romano C, Castiglia L, Bottitta M, Dhar SU, Erwin DJ, Emrick L, Keren B, Afenjar A, Zhu B, Bai B, Stankiewicz P, Herman K; University of Washington Center for Mendelian Genomics, Mercimek-Andrews S, Juusola J, Wilfert AB, Abou Jamra R, Büttner B, Mefford HC, Muir AM, Scheffer IE, Regan BM, Malone S, Gecz J, Cobben J, Weiss MM, Waisfisz Q, Bijlsma EK, Hoffer MJV, Ruivenkamp CAL, Sartori S, Xia F, Rosenfeld JA, Bernier RA, Wangler MF, Yamamoto S, Xia K, Stegmann APA, Bellen HJ, Murgia A, Eichler EE
Nat Commun 2019 Oct 15;10(1):4679. doi: 10.1038/s41467-019-12435-8. PMID: 31616000Free PMC Article
Earl RK, Turner TN, Mefford HC, Hudac CM, Gerdts J, Eichler EE, Bernier RA
Mol Autism 2017;8:54. Epub 2017 Oct 5 doi: 10.1186/s13229-017-0173-5. PMID: 29034068Free PMC Article
Battaglia A
Orphanet J Rare Dis 2008 Nov 19;3:30. doi: 10.1186/1750-1172-3-30. PMID: 19019226Free PMC Article

Recent systematic reviews

Leader G, Abberton C, Cunningham S, Gilmartin K, Grudzien M, Higgins E, Joshi L, Whelan S, Mannion A
Nutrients 2022 Apr 1;14(7) doi: 10.3390/nu14071471. PMID: 35406084Free PMC Article
Lukito S, Norman L, Carlisi C, Radua J, Hart H, Simonoff E, Rubia K
Psychol Med 2020 Apr;50(6):894-919. Epub 2020 Mar 27 doi: 10.1017/S0033291720000574. PMID: 32216846Free PMC Article
Reichow B, Hume K, Barton EE, Boyd BA
Cochrane Database Syst Rev 2018 May 9;5(5):CD009260. doi: 10.1002/14651858.CD009260.pub3. PMID: 29742275Free PMC Article
Baumel A, Pawar A, Mathur N, Kane JM, Correll CU
J Clin Psychiatry 2017 Sep/Oct;78(8):e957-e969. doi: 10.4088/JCP.16r11063. PMID: 28493653
Maber-Aleksandrowicz S, Avent C, Hassiotis A
Res Dev Disabil 2016 Feb-Mar;49-50:322-38. Epub 2016 Jan 7 doi: 10.1016/j.ridd.2015.12.005. PMID: 26773215

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