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Intellectual disability, autosomal recessive 6(MRT6)

MedGen UID:
370848
Concept ID:
C1970198
Mental or Behavioral Dysfunction
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 6; MRT6
 
Gene (location): GRIK2 (6q16.3)
 
Monarch Initiative: MONDO:0012614
OMIM®: 611092

Definition

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the GRIK2 gene. [from MONDO]

Clinical features

From HPO
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
Atonic seizure
MedGen UID:
78735
Concept ID:
C0270846
Disease or Syndrome
Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.
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.
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.
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.
Kinetic tremor
MedGen UID:
1638576
Concept ID:
C4551521
Sign or Symptom
Tremor that occurs during any voluntary movement. It may include visually or non-visually guided movements. Tremor during target directed movement is called intention tremor.
Reduced social responsiveness
MedGen UID:
1841569
Concept ID:
C5826975
Finding
A reduced ability to participate in the back-and-forth flow of social interaction appropriate to culture and developmental level, which is normally characterized by an influence of the behavior of one person on the behavior of another person. This results in difficulty interacting with others through emotional, physical, or verbal communication.

Professional guidelines

PubMed

Langhammer F, Maroofian R, Badar R, Gregor A, Rochman M, Ratliff JB, Koopmans M, Herget T, Hempel M, Kortüm F, Heron D, Mignot C, Keren B, Brooks S, Botti C, Ben-Zeev B, Argilli E, Sherr EH, Gowda VK, Srinivasan VM, Bakhtiari S, Kruer MC, Salih MA, Kuechler A, Muller EA, Blocker K, Kuismin O, Park KL, Kochhar A, Brown K, Ramanathan S, Clark RD, Elgizouli M, Melikishvili G, Tabatadze N, Stark Z, Mirzaa GM, Ong J, Grasshoff U, Bevot A, von Wintzingerode L, Jamra RA, Hennig Y, Goldenberg P, Al Alam C, Charif M, Boulouiz R, Bellaoui M, Amrani R, Al Mutairi F, Tamim AM, Abdulwahab F, Alkuraya FS, Khouj EM, Alvi JR, Sultan T, Hashemi N, Karimiani EG, Ashrafzadeh F, Imannezhad S, Efthymiou S, Houlden H, Sticht H, Zweier C
Genet Med 2023 Aug;25(8):100885. Epub 2023 May 8 doi: 10.1016/j.gim.2023.100885. PMID: 37165955
Shang S, Mei Y, Wang T, Zheng X, Chen K, Xiong S, Dong Y, Chang Y, Wu X, Kong X, Tan M, Wu L, Zhang Y, Xiao Y, Xie Y, Cai G, Chen X, Li Q
Clin Nephrol 2022 Jun;97(6):328-338. doi: 10.5414/CN110476. PMID: 35142283
Salen G, Steiner RD
J Inherit Metab Dis 2017 Nov;40(6):771-781. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0093-8. PMID: 28980151

Recent clinical studies

Etiology

Dolu MH, Öz Tunçer G, Akça Ü, Aydın S, Bahadir O, Sezer Ö, Aksoy A, Taşdemir HA
J Child Neurol 2024 Jun;39(7-8):260-267. Epub 2024 Jul 25 doi: 10.1177/08830738241263243. PMID: 39051604
Tremblay M, Girard-Côté L, Brais B, Gagnon C
Orphanet J Rare Dis 2022 Oct 1;17(1):369. doi: 10.1186/s13023-022-02497-1. PMID: 36183078Free PMC Article
Santos M, Damásio J, Carmona S, Neto JL, Dehghani N, Guedes LC, Barbot C, Barros J, Brás J, Sequeiros J, Guerreiro R
Cells 2022 Mar 12;11(6) doi: 10.3390/cells11060981. PMID: 35326432Free PMC Article
Zalewski CK, Sydlowski SA, King KA, Bianconi S, Dang Do A, Porter FD, Brewer CC
Am J Med Genet A 2021 Apr;185(4):1131-1141. Epub 2021 Feb 2 doi: 10.1002/ajmg.a.62087. PMID: 33529473Free PMC Article
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948

Diagnosis

Dolu MH, Öz Tunçer G, Akça Ü, Aydın S, Bahadir O, Sezer Ö, Aksoy A, Taşdemir HA
J Child Neurol 2024 Jun;39(7-8):260-267. Epub 2024 Jul 25 doi: 10.1177/08830738241263243. PMID: 39051604
Saleh S, Beyyumi E, Al Kaabi A, Hertecant J, Barakat D, Al Dhaheri NS, Al-Gazali L, Al Shamsi A
Clin Genet 2021 Nov;100(5):573-600. Epub 2021 Aug 19 doi: 10.1111/cge.14044. PMID: 34374989
Zalewski CK, Sydlowski SA, King KA, Bianconi S, Dang Do A, Porter FD, Brewer CC
Am J Med Genet A 2021 Apr;185(4):1131-1141. Epub 2021 Feb 2 doi: 10.1002/ajmg.a.62087. PMID: 33529473Free PMC Article
Reuter MS, Tawamie H, Buchert R, Hosny Gebril O, Froukh T, Thiel C, Uebe S, Ekici AB, Krumbiegel M, Zweier C, Hoyer J, Eberlein K, Bauer J, Scheller U, Strom TM, Hoffjan S, Abdelraouf ER, Meguid NA, Abboud A, Al Khateeb MA, Fakher M, Hamdan S, Ismael A, Muhammad S, Abdallah E, Sticht H, Wieczorek D, Reis A, Abou Jamra R
JAMA Psychiatry 2017 Mar 1;74(3):293-299. doi: 10.1001/jamapsychiatry.2016.3798. PMID: 28097321
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948

Therapy

Malekkou A, Tomazou M, Mavrikiou G, Dionysiou M, Georgiou T, Papaevripidou I, Alexandrou A, Sismani C, Drousiotou A, Grafakou O, Petrou PP
BMC Med Genomics 2024 Mar 25;17(1):78. doi: 10.1186/s12920-024-01846-2. PMID: 38528593Free PMC Article
Yunisova G, Tufekcioglu Z, Dogu O, Bilgic B, Kaleagasi H, Akca Kalem S, Lohmann E, Gurvit HI, Emre M, Hanagasi HA
Neurodegener Dis 2019;19(5-6):218-224. Epub 2020 Apr 29 doi: 10.1159/000506770. PMID: 32349000
Salen G, Steiner RD
J Inherit Metab Dis 2017 Nov;40(6):771-781. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0093-8. PMID: 28980151
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948
Robinson BH, MacKay N, Chun K, Ling M
J Inherit Metab Dis 1996;19(4):452-62. doi: 10.1007/BF01799106. PMID: 8884569

Prognosis

Dolu MH, Öz Tunçer G, Akça Ü, Aydın S, Bahadir O, Sezer Ö, Aksoy A, Taşdemir HA
J Child Neurol 2024 Jun;39(7-8):260-267. Epub 2024 Jul 25 doi: 10.1177/08830738241263243. PMID: 39051604
Bayat A, de Valles-Ibáñez G, Pendziwiat M, Knaus A, Alt K, Biamino E, Bley A, Calvert S, Carney P, Caro-Llopis A, Ceulemans B, Cousin J, Davis S, des Portes V, Edery P, England E, Ferreira C, Freeman J, Gener B, Gorce M, Heron D, Hildebrand MS, Jezela-Stanek A, Jouk PS, Keren B, Kloth K, Kluger G, Kuhn M, Lemke JR, Li H, Martinez F, Maxton C, Mefford HC, Merla G, Mierzewska H, Muir A, Monfort S, Nicolai J, Norman J, O'Grady G, Oleksy B, Orellana C, Orec LE, Peinhardt C, Pronicka E, Rosello M, Santos-Simarro F, Schwaibold EMC, Stegmann APA, Stumpel CT, Szczepanik E, Terczyńska I, Thevenon J, Tzschach A, Van Bogaert P, Vittorini R, Walsh S, Weckhuysen S, Weissman B, Wolfe L, Reymond A, De Nittis P, Poduri A, Olson H, Striano P, Lesca G, Scheffer IE, Møller RS, Sadleir LG
Epilepsia 2022 Apr;63(4):974-991. Epub 2022 Feb 18 doi: 10.1111/epi.17173. PMID: 35179230
Abusrair A, AlHamoud I, Bohlega S
J Clin Neurophysiol 2022 Sep 1;39(6):504-509. Epub 2020 Dec 30 doi: 10.1097/WNP.0000000000000811. PMID: 33417382
Yunisova G, Tufekcioglu Z, Dogu O, Bilgic B, Kaleagasi H, Akca Kalem S, Lohmann E, Gurvit HI, Emre M, Hanagasi HA
Neurodegener Dis 2019;19(5-6):218-224. Epub 2020 Apr 29 doi: 10.1159/000506770. PMID: 32349000
Salen G, Steiner RD
J Inherit Metab Dis 2017 Nov;40(6):771-781. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0093-8. PMID: 28980151

Clinical prediction guides

Kaiyrzhanov R, Ortigoza-Escobar JD, Stringer BW, Ganieva M, Gowda VK, Srinivasan VM, Macaya A, Laner A, Onbool E, Al-Shammari R, Al-Owain M, Deconinck N, Vilain C, Dontaine P, Self E, Akram R, Hussain G, Baig SM, Iqbal J, Salpietro V, Neshatdoust M, Kasiri M, Yesil G, Uygur T, Pysden K, Berry IR, Alves CA, Giacomotto J, Houlden H, Maroofian R
Mov Disord 2024 Jun;39(6):983-995. Epub 2024 Apr 6 doi: 10.1002/mds.29754. PMID: 38581205
Langhammer F, Maroofian R, Badar R, Gregor A, Rochman M, Ratliff JB, Koopmans M, Herget T, Hempel M, Kortüm F, Heron D, Mignot C, Keren B, Brooks S, Botti C, Ben-Zeev B, Argilli E, Sherr EH, Gowda VK, Srinivasan VM, Bakhtiari S, Kruer MC, Salih MA, Kuechler A, Muller EA, Blocker K, Kuismin O, Park KL, Kochhar A, Brown K, Ramanathan S, Clark RD, Elgizouli M, Melikishvili G, Tabatadze N, Stark Z, Mirzaa GM, Ong J, Grasshoff U, Bevot A, von Wintzingerode L, Jamra RA, Hennig Y, Goldenberg P, Al Alam C, Charif M, Boulouiz R, Bellaoui M, Amrani R, Al Mutairi F, Tamim AM, Abdulwahab F, Alkuraya FS, Khouj EM, Alvi JR, Sultan T, Hashemi N, Karimiani EG, Ashrafzadeh F, Imannezhad S, Efthymiou S, Houlden H, Sticht H, Zweier C
Genet Med 2023 Aug;25(8):100885. Epub 2023 May 8 doi: 10.1016/j.gim.2023.100885. PMID: 37165955
Bayat A, de Valles-Ibáñez G, Pendziwiat M, Knaus A, Alt K, Biamino E, Bley A, Calvert S, Carney P, Caro-Llopis A, Ceulemans B, Cousin J, Davis S, des Portes V, Edery P, England E, Ferreira C, Freeman J, Gener B, Gorce M, Heron D, Hildebrand MS, Jezela-Stanek A, Jouk PS, Keren B, Kloth K, Kluger G, Kuhn M, Lemke JR, Li H, Martinez F, Maxton C, Mefford HC, Merla G, Mierzewska H, Muir A, Monfort S, Nicolai J, Norman J, O'Grady G, Oleksy B, Orellana C, Orec LE, Peinhardt C, Pronicka E, Rosello M, Santos-Simarro F, Schwaibold EMC, Stegmann APA, Stumpel CT, Szczepanik E, Terczyńska I, Thevenon J, Tzschach A, Van Bogaert P, Vittorini R, Walsh S, Weckhuysen S, Weissman B, Wolfe L, Reymond A, De Nittis P, Poduri A, Olson H, Striano P, Lesca G, Scheffer IE, Møller RS, Sadleir LG
Epilepsia 2022 Apr;63(4):974-991. Epub 2022 Feb 18 doi: 10.1111/epi.17173. PMID: 35179230
Abusrair A, AlHamoud I, Bohlega S
J Clin Neurophysiol 2022 Sep 1;39(6):504-509. Epub 2020 Dec 30 doi: 10.1097/WNP.0000000000000811. PMID: 33417382
Zalewski CK, Sydlowski SA, King KA, Bianconi S, Dang Do A, Porter FD, Brewer CC
Am J Med Genet A 2021 Apr;185(4):1131-1141. Epub 2021 Feb 2 doi: 10.1002/ajmg.a.62087. PMID: 33529473Free PMC Article

Recent systematic reviews

Kiaee F, Zaki-Dizaji M, Hafezi N, Almasi-Hashiani A, Hamedifar H, Sabzevari A, Shirkani A, Zian Z, Jadidi-Niaragh F, Aghamahdi F, Goudarzvand M, Yazdani R, Abolhassani H, Aghamohammadi A, Azizi G
Endocr Metab Immune Disord Drug Targets 2021;21(4):664-672. doi: 10.2174/1871530320666200613204426. PMID: 32533820

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