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Intellectual developmental disorder, autosomal recessive 76(MRT76)

MedGen UID:
1808571
•Concept ID:
C5677007
•
Mental or Behavioral Dysfunction
Synonyms: MENTAL RETARDATION, AUTOSOMAL RECESSIVE 76; MRT76
 
Gene (location): GRIA1 (5q33.2)
 
Monarch Initiative: MONDO:0030968
OMIM®: 619931

Definition

Autosomal recessive intellectual developmental disorder-76 (MRT76) is characterized by impaired intellectual development, absent speech, poor sleep, abnormal EEG with seizures, normal brain imaging, and precocious puberty (Ismail et al., 2022). [from OMIM]

Clinical features

From HPO
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.
See: Feature record | Search on this feature
Chronic constipation
MedGen UID:
98325
•Concept ID:
C0401149
•
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Intellectual disability, severe
MedGen UID:
48638
•Concept ID:
C0036857
•
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
See: Feature record | Search on this feature
Sleep abnormality
MedGen UID:
52372
•Concept ID:
C0037317
•
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
See: Feature record | Search on this feature
Self-injurious behavior
MedGen UID:
88371
•Concept ID:
C0085271
•
Individual Behavior
Self-aggression.
See: Search on this feature
Absent speech
MedGen UID:
340737
•Concept ID:
C1854882
•
Finding
Complete lack of development of speech and language abilities.
See: Feature record | Search on this feature
Interictal epileptiform activity
MedGen UID:
869073
•Concept ID:
C4023491
•
Finding
Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure.
See: Feature record | Search on this feature
Delayed fine motor development
MedGen UID:
869257
•Concept ID:
C4023681
•
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands.
See: Feature record | Search on this feature
Precocious puberty in females
MedGen UID:
543449
•Concept ID:
C0271616
•
Disease or Syndrome
The onset of puberty before the age of 8 years in girls.
See: Feature record | Search on this feature
Exodeviation
MedGen UID:
1637525
•Concept ID:
C4551670
•
Disease or Syndrome
A manifest or latent ocular deviation in which one or both eyes tends to deviate temporally.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model.
Deng R, Medico-Salsench E, Nikoncuk A, Ramakrishnan R, Lanko K, Kühn NA, van der Linde HC, Lor-Zade S, Albuainain F, Shi Y, Yousefi S, Capo I, van den Herik EM, van Slegtenhorst M, van Minkelen R, Geeven G, Mulder MT, Ruijter GJG, Lütjohann D, Jacobs EH, Houlden H, Pagnamenta AT, Metcalfe K, Jackson A, Banka S, De Simone L, Schwaede A, Kuntz N, Palculict TB, Abbas S, Umair M, AlMuhaizea M, Colak D, AlQudairy H, Alsagob M, Pereira C, Trunzo R, Karageorgou V, Bertoli-Avella AM, Bauer P, Bouman A, Hoefsloot LH, van Ham TJ, Issa M, Zaki MS, Gleeson JG, Willemsen R, Kaya N, Arold ST, Maroofian R, Sanderson LE, Barakat TS
Acta Neuropathol 2023 Aug;146(2):353-368. Epub 2023 Apr 29 doi: 10.1007/s00401-023-02579-9. PMID: 37119330Free PMC Article
Autosomal-recessive omodysplasia: prenatal diagnosis and histomorphometric assessment of the physeal plates of the long bones.
Borochowitz Z, Sabo E, Misselevitch I, Boss JH
Am J Med Genet 1998 Mar 19;76(3):238-44. doi: 10.1002/(sici)1096-8628(19980319)76:3<238::aid-ajmg7>3.0.co;2-m. PMID: 9508243

Recent clinical studies

Etiology

Audiological and radiological study of eight polish patients with alpha-mannosidosis.
Iwanicka-Pronicka K, Guzek A, Sarnecki J, Tylki-Szymańska A
Int J Pediatr Otorhinolaryngol 2023 Jun;169:111556. Epub 2023 Apr 17 doi: 10.1016/j.ijporl.2023.111556. PMID: 37099947
Bardet Biedl syndrome in South Africa: A single founder mutation.
Fieggen K, Milligan C, Henderson B, Esterhuizen AI
S Afr Med J 2016 May 25;106(6 Suppl 1):S72-4. doi: 10.7196/SAMJ.2016.v106i6.11000. PMID: 27245532
Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting.
Klebe S, Stevanin G, Depienne C
Rev Neurol (Paris) 2015 Jun-Jul;171(6-7):505-30. Epub 2015 May 23 doi: 10.1016/j.neurol.2015.02.017. PMID: 26008818
Clinical whole exome sequencing in child neurology practice.
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622
Smith-Lemli-Opitz syndrome: Objective assessment of facial phenotype.
Nowaczyk MJ, Tan M, Hamid JS, Allanson JE
Am J Med Genet A 2012 May;158A(5):1020-8. Epub 2012 Mar 21 doi: 10.1002/ajmg.a.35285. PMID: 22438180

Diagnosis

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.
Maroofian R, Kaiyrzhanov R, Cali E, Zamani M, Zaki MS, Ferla M, Tortora D, Sadeghian S, Saadi SM, Abdullah U, Karimiani EG, Efthymiou S, Yeşil G, Alavi S, Al Shamsi AM, Tajsharghi H, Abdel-Hamid MS, Saadi NW, Al Mutairi F, Alabdi L, Beetz C, Ali Z, Toosi MB, Rudnik-Schöneborn S, Babaei M, Isohanni P, Muhammad J, Khan S, Al Shalan M, Hickey SE, Marom D, Elhanan E, Kurian MA, Marafi D, Saberi A, Hamid M, Spaull R, Meng L, Lalani S, Maqbool S, Rahman F, Seeger J, Palculict TB, Lau T, Murphy D, Mencacci NE, Steindl K, Begemann A, Rauch A, Akbas S, Aslanger AD, Salpietro V, Yousaf H, Ben-Shachar S, Ejeskär K, Al Aqeel AI, High FA, Armstrong-Javors AE, Zahraei SM, Seifi T, Zeighami J, Shariati G, Sedaghat A, Asl SN, Shahrooei M, Zifarelli G, Burglen L, Ravelli C, Zschocke J, Schatz UA, Ghavideldarestani M, Kamel WA, Van Esch H, Hackenberg A, Taylor JC, Al-Gazali L, Bauer P, Gleeson JJ, Alkuraya FS, Lupski JR, Galehdari H, Azizimalamiri R, Chung WK, Baig SM, Houlden H, Severino M
Brain 2023 Dec 1;146(12):5031-5043. doi: 10.1093/brain/awad257. PMID: 37517035Free PMC Article
Spectrum of neuro-genetic disorders in the United Arab Emirates national population.
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
Molecular genetics of the POMT1-related muscular dystrophy-dystroglycanopathies.
Hu P, Yuan L, Deng H
Mutat Res Rev Mutat Res 2018 Oct-Dec;778:45-50. Epub 2018 Sep 12 doi: 10.1016/j.mrrev.2018.09.002. PMID: 30454682
Brain MR Imaging Findings in Woodhouse-Sakati Syndrome.
Abusrair AH, Bohlega S, Al-Semari A, Al-Ajlan FS, Al-Ahmadi K, Mohamed B, AlDakheel A
AJNR Am J Neuroradiol 2018 Dec;39(12):2256-2262. Epub 2018 Nov 8 doi: 10.3174/ajnr.A5879. PMID: 30409855Free PMC Article
Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting.
Klebe S, Stevanin G, Depienne C
Rev Neurol (Paris) 2015 Jun-Jul;171(6-7):505-30. Epub 2015 May 23 doi: 10.1016/j.neurol.2015.02.017. PMID: 26008818

Therapy

AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model.
Deng R, Medico-Salsench E, Nikoncuk A, Ramakrishnan R, Lanko K, Kühn NA, van der Linde HC, Lor-Zade S, Albuainain F, Shi Y, Yousefi S, Capo I, van den Herik EM, van Slegtenhorst M, van Minkelen R, Geeven G, Mulder MT, Ruijter GJG, Lütjohann D, Jacobs EH, Houlden H, Pagnamenta AT, Metcalfe K, Jackson A, Banka S, De Simone L, Schwaede A, Kuntz N, Palculict TB, Abbas S, Umair M, AlMuhaizea M, Colak D, AlQudairy H, Alsagob M, Pereira C, Trunzo R, Karageorgou V, Bertoli-Avella AM, Bauer P, Bouman A, Hoefsloot LH, van Ham TJ, Issa M, Zaki MS, Gleeson JG, Willemsen R, Kaya N, Arold ST, Maroofian R, Sanderson LE, Barakat TS
Acta Neuropathol 2023 Aug;146(2):353-368. Epub 2023 Apr 29 doi: 10.1007/s00401-023-02579-9. PMID: 37119330Free PMC Article
Clinical whole exome sequencing in child neurology practice.
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622

Prognosis

Audiological and radiological study of eight polish patients with alpha-mannosidosis.
Iwanicka-Pronicka K, Guzek A, Sarnecki J, Tylki-Szymańska A
Int J Pediatr Otorhinolaryngol 2023 Jun;169:111556. Epub 2023 Apr 17 doi: 10.1016/j.ijporl.2023.111556. PMID: 37099947
Phenotype and mutation expansion of the PTPN23 associated disorder characterized by neurodevelopmental delay and structural brain abnormalities.
Bend R, Cohen L, Carter MT, Lyons MJ, Niyazov D, Mikati MA, Rojas SK, Person RE, Si Y, Wentzensen IM; Regeneron Genetics Center, Torti E, Lee JA, Boycott KM, Basel-Salmon L, Ferreira CR, Gonzaga-Jauregui C
Eur J Hum Genet 2020 Jan;28(1):76-87. Epub 2019 Aug 8 doi: 10.1038/s41431-019-0487-1. PMID: 31395947Free PMC Article
Clinical whole exome sequencing in child neurology practice.
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622
The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.
Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, Romano DM, Parano E, Pavone L, Brzustowicz LM
Nat Genet 1993 Dec;5(4):344-50. doi: 10.1038/ng1293-344. PMID: 8298641

Clinical prediction guides

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.
Maroofian R, Kaiyrzhanov R, Cali E, Zamani M, Zaki MS, Ferla M, Tortora D, Sadeghian S, Saadi SM, Abdullah U, Karimiani EG, Efthymiou S, Yeşil G, Alavi S, Al Shamsi AM, Tajsharghi H, Abdel-Hamid MS, Saadi NW, Al Mutairi F, Alabdi L, Beetz C, Ali Z, Toosi MB, Rudnik-Schöneborn S, Babaei M, Isohanni P, Muhammad J, Khan S, Al Shalan M, Hickey SE, Marom D, Elhanan E, Kurian MA, Marafi D, Saberi A, Hamid M, Spaull R, Meng L, Lalani S, Maqbool S, Rahman F, Seeger J, Palculict TB, Lau T, Murphy D, Mencacci NE, Steindl K, Begemann A, Rauch A, Akbas S, Aslanger AD, Salpietro V, Yousaf H, Ben-Shachar S, Ejeskär K, Al Aqeel AI, High FA, Armstrong-Javors AE, Zahraei SM, Seifi T, Zeighami J, Shariati G, Sedaghat A, Asl SN, Shahrooei M, Zifarelli G, Burglen L, Ravelli C, Zschocke J, Schatz UA, Ghavideldarestani M, Kamel WA, Van Esch H, Hackenberg A, Taylor JC, Al-Gazali L, Bauer P, Gleeson JJ, Alkuraya FS, Lupski JR, Galehdari H, Azizimalamiri R, Chung WK, Baig SM, Houlden H, Severino M
Brain 2023 Dec 1;146(12):5031-5043. doi: 10.1093/brain/awad257. PMID: 37517035Free PMC Article
AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model.
Deng R, Medico-Salsench E, Nikoncuk A, Ramakrishnan R, Lanko K, Kühn NA, van der Linde HC, Lor-Zade S, Albuainain F, Shi Y, Yousefi S, Capo I, van den Herik EM, van Slegtenhorst M, van Minkelen R, Geeven G, Mulder MT, Ruijter GJG, Lütjohann D, Jacobs EH, Houlden H, Pagnamenta AT, Metcalfe K, Jackson A, Banka S, De Simone L, Schwaede A, Kuntz N, Palculict TB, Abbas S, Umair M, AlMuhaizea M, Colak D, AlQudairy H, Alsagob M, Pereira C, Trunzo R, Karageorgou V, Bertoli-Avella AM, Bauer P, Bouman A, Hoefsloot LH, van Ham TJ, Issa M, Zaki MS, Gleeson JG, Willemsen R, Kaya N, Arold ST, Maroofian R, Sanderson LE, Barakat TS
Acta Neuropathol 2023 Aug;146(2):353-368. Epub 2023 Apr 29 doi: 10.1007/s00401-023-02579-9. PMID: 37119330Free PMC Article
Audiological and radiological study of eight polish patients with alpha-mannosidosis.
Iwanicka-Pronicka K, Guzek A, Sarnecki J, Tylki-Szymańska A
Int J Pediatr Otorhinolaryngol 2023 Jun;169:111556. Epub 2023 Apr 17 doi: 10.1016/j.ijporl.2023.111556. PMID: 37099947
Phenotype and mutation expansion of the PTPN23 associated disorder characterized by neurodevelopmental delay and structural brain abnormalities.
Bend R, Cohen L, Carter MT, Lyons MJ, Niyazov D, Mikati MA, Rojas SK, Person RE, Si Y, Wentzensen IM; Regeneron Genetics Center, Torti E, Lee JA, Boycott KM, Basel-Salmon L, Ferreira CR, Gonzaga-Jauregui C
Eur J Hum Genet 2020 Jan;28(1):76-87. Epub 2019 Aug 8 doi: 10.1038/s41431-019-0487-1. PMID: 31395947Free PMC Article
Brain MR Imaging Findings in Woodhouse-Sakati Syndrome.
Abusrair AH, Bohlega S, Al-Semari A, Al-Ajlan FS, Al-Ahmadi K, Mohamed B, AlDakheel A
AJNR Am J Neuroradiol 2018 Dec;39(12):2256-2262. Epub 2018 Nov 8 doi: 10.3174/ajnr.A5879. PMID: 30409855Free PMC Article

Recent systematic reviews

Endocrine disorders in Woodhouse-Sakati syndrome: a systematic review of the literature.
Agopiantz M, Corbonnois P, Sorlin A, Bonnet C, Klein M, Hubert N, Pascal-Vigneron V, Jonveaux P, Cuny T, Leheup B, Weryha G
J Endocrinol Invest 2014 Jan;37(1):1-7. Epub 2014 Jan 8 doi: 10.1007/s40618-013-0001-5. PMID: 24464444

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