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Intellectual disability, autosomal recessive 34(MRT34)

MedGen UID:
482674
•Concept ID:
C3281044
•
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 34, WITH VARIANT LISSENCEPHALY; MRT34
 
Gene (location): CRADD (12q22)
 
Monarch Initiative: MONDO:0013785
OMIM®: 614499

Definition

MRT34 is an autosomal recessive neurologic disorder characterized by mildly to moderately impaired intellectual development and megalencephaly or enlarged head circumference. Brain imaging shows a mild variant of lissencephaly with anterior-predominant pachygyria with shallow and unusually wide sulci and mildly thickened cortex. Some patients may have seizures (summary by Di Donato et al., 2016). [from OMIM]

Clinical features

From HPO
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
Megalencephaly
MedGen UID:
65141
•Concept ID:
C0221355
•
Congenital Abnormality
Diffuse enlargement of the entire cerebral hemispheres leading to macrocephaly (with or without overlying cortical dysplasia).
See: Feature record | Search on this feature
Lissencephaly
MedGen UID:
78604
•Concept ID:
C0266463
•
Finding
A spectrum of malformations of cortical development caused by insufficient neuronal migration that subsumes the terms agyria, pachygyria and subcortical band heterotopia. See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
See: Feature record | Search on this feature
Macrogyria
MedGen UID:
120579
•Concept ID:
C0266483
•
Congenital Abnormality
Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Increased head circumference
MedGen UID:
909477
•Concept ID:
C4083076
•
Finding
An abnormally increased head circumference in a growing child. Head circumference is measured with a nonelastic tape and comprises the distance from above the eyebrows and ears and around the back of the head. The measured HC is then plotted on an appropriate growth chart.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVIntellectual disability, autosomal recessive 34

Professional guidelines

PubMed

Clinical utility of exome sequencing in individuals with large homozygous regions detected by chromosomal microarray analysis.
Prasad A, Sdano MA, Vanzo RJ, Mowery-Rushton PA, Serrano MA, Hensel CH, Wassman ER
BMC Med Genet 2018 Mar 20;19(1):46. doi: 10.1186/s12881-018-0555-3. PMID: 29554876Free PMC Article
Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.
Handley MT, Morris-Rosendahl DJ, Brown S, Macdonald F, Hardy C, Bem D, Carpanini SM, Borck G, Martorell L, Izzi C, Faravelli F, Accorsi P, Pinelli L, Basel-Vanagaite L, Peretz G, Abdel-Salam GM, Zaki MS, Jansen A, Mowat D, Glass I, Stewart H, Mancini G, Lederer D, Roscioli T, Giuliano F, Plomp AS, Rolfs A, Graham JM, Seemanova E, Poo P, García-Cazorla A, Edery P, Jackson IJ, Maher ER, Aligianis IA
Hum Mutat 2013 May;34(5):686-96. doi: 10.1002/humu.22296. PMID: 23420520

Recent clinical studies

Etiology

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Neurocognitive, adaptive, and psychosocial functioning in individuals with Robinow syndrome.
Schwartz DD, Fein RH, Carvalho CMB, Sutton VR, Mazzeu JF, Axelrad ME
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Patterns of neurological manifestations in Woodhouse-Sakati Syndrome.
Bohlega S, Abusrair AH, Al-Ajlan FS, Alharbi N, Al-Semari A, Bohlega B, Abualsaud D, Alkuraya F
Parkinsonism Relat Disord 2019 Dec;69:99-103. Epub 2019 Oct 13 doi: 10.1016/j.parkreldis.2019.10.007. PMID: 31726291
Genetics of autosomal recessive non-syndromic mental retardation: recent advances.
Basel-Vanagaite L
Clin Genet 2007 Sep;72(3):167-74. doi: 10.1111/j.1399-0004.2007.00881.x. PMID: 17718851

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
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The epilepsy phenotype of ST3GAL3-related developmental and epileptic encephalopathy.
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Epilepsia Open 2023 Jun;8(2):623-632. Epub 2023 Apr 24 doi: 10.1002/epi4.12747. PMID: 37067065Free PMC Article
OTUD6B-associated intellectual disability: novel variants and genetic exclusion of retinal degeneration as part of a refined phenotype.
Abdel-Salam GMH, Abdel-Hamid MS, Sayed ISM, Zechner U, Bolz HJ
J Hum Genet 2022 Jan;67(1):55-64. Epub 2021 Aug 5 doi: 10.1038/s10038-021-00966-2. PMID: 34354232
Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.
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
The eye and the skin in nonendocrine metabolic disorders.
Urrets-Zavalía JA, Espósito E, Garay I, Monti R, Ruiz-Lascano A, Correa L, Serra HM, Grzybowski A
Clin Dermatol 2016 Mar-Apr;34(2):166-82. Epub 2015 Dec 7 doi: 10.1016/j.clindermatol.2015.12.002. PMID: 26903184

Therapy

A syndrome including thumb malformations, microcephaly, short stature, and hypogonadism.
Zlotogora J, Dagan J, Ganen A, Abu-Libdeh M, Ben-Neriah Z, Cohen T
J Med Genet 1997 Oct;34(10):813-6. doi: 10.1136/jmg.34.10.813. PMID: 9350812Free PMC Article

Prognosis

PIGN encephalopathy: Characterizing the epileptology.
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Mucopolysaccharidosis III in Mainland China: natural history, clinical and molecular characteristics of 34 patients.
Kong W, Meng Y, Zou L, Yang G, Wang J, Shi X
J Pediatr Endocrinol Metab 2020 May 24;33(6):793-802. doi: 10.1515/jpem-2019-0505. PMID: 32447333
Patterns of neurological manifestations in Woodhouse-Sakati Syndrome.
Bohlega S, Abusrair AH, Al-Ajlan FS, Alharbi N, Al-Semari A, Bohlega B, Abualsaud D, Alkuraya F
Parkinsonism Relat Disord 2019 Dec;69:99-103. Epub 2019 Oct 13 doi: 10.1016/j.parkreldis.2019.10.007. PMID: 31726291
A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome.
Pohl E, Aykut A, Beleggia F, Karaca E, Durmaz B, Keupp K, Arslan E, Palamar M, Yigit G, Özkinay F, Wollnik B
Hum Genet 2013 Nov;132(11):1311-20. Epub 2013 Jul 13 doi: 10.1007/s00439-013-1337-9. PMID: 23851939
Warburg Micro syndrome.
Dursun F, Güven A, Morris-Rosendahl D
J Pediatr Endocrinol Metab 2012;25(3-4):379-82. doi: 10.1515/jpem-2011-0459. PMID: 22768674

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
The epilepsy phenotype of ST3GAL3-related developmental and epileptic encephalopathy.
Whitney R, Jain P, RamachandranNair R, Jones KC, Kiani H, Tarnopolsky M, Meaney B
Epilepsia Open 2023 Jun;8(2):623-632. Epub 2023 Apr 24 doi: 10.1002/epi4.12747. PMID: 37067065Free PMC Article
PIGN encephalopathy: Characterizing the epileptology.
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
Mucopolysaccharidosis III in Mainland China: natural history, clinical and molecular characteristics of 34 patients.
Kong W, Meng Y, Zou L, Yang G, Wang J, Shi X
J Pediatr Endocrinol Metab 2020 May 24;33(6):793-802. doi: 10.1515/jpem-2019-0505. PMID: 32447333
Progressive hereditary spastic paraplegia caused by a homozygous KY mutation.
Yogev Y, Perez Y, Noyman I, Madegem AA, Flusser H, Shorer Z, Cohen E, Kachko L, Michaelovsky A, Birk R, Koifman A, Drabkin M, Wormser O, Halperin D, Kadir R, Birk OS
Eur J Hum Genet 2017 Aug;25(8):966-972. Epub 2017 May 10 doi: 10.1038/ejhg.2017.85. PMID: 28488683Free PMC Article

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