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Intellectual disability, autosomal recessive 44(MRT44)

MedGen UID:
863182
Concept ID:
C4014745
Mental or Behavioral Dysfunction
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 44; MRT44
 
Gene (location): METTL23 (17q25.1)
 
Monarch Initiative: MONDO:0014409
OMIM®: 615942

Definition

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the METTL23 gene. [from MONDO]

Clinical features

From HPO
Shawl scrotum
MedGen UID:
388088
Concept ID:
C1858539
Congenital Abnormality
Superior margin of the scrotum superior to the base of the penis.
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
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.
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.
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.
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.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.

Professional guidelines

PubMed

Toktaş İ, Sarıbaş S, Canpolat S, Erdem Ö, Özbek MN
Turk J Pediatr 2022;64(6):985-992. doi: 10.24953/turkjped.2022.467. PMID: 36583880
Coughlin CR 2nd, Tseng LA, Abdenur JE, Ashmore C, Boemer F, Bok LA, Boyer M, Buhas D, Clayton PT, Das A, Dekker H, Evangeliou A, Feillet F, Footitt EJ, Gospe SM Jr, Hartmann H, Kara M, Kristensen E, Lee J, Lilje R, Longo N, Lunsing RJ, Mills P, Papadopoulou MT, Pearl PL, Piazzon F, Plecko B, Saini AG, Santra S, Sjarif DR, Stockler-Ipsiroglu S, Striano P, Van Hove JLK, Verhoeven-Duif NM, Wijburg FA, Zuberi SM, van Karnebeek CDM
J Inherit Metab Dis 2021 Jan;44(1):178-192. Epub 2020 Dec 1 doi: 10.1002/jimd.12332. PMID: 33200442
Botta E, Offman J, Nardo T, Ricotti R, Zambruno G, Sansone D, Balestri P, Raams A, Kleijer WJ, Jaspers NG, Sarasin A, Lehmann AR, Stefanini M
Hum Mutat 2007 Jan;28(1):92-6. doi: 10.1002/humu.20419. PMID: 16977596

Recent clinical studies

Etiology

Masri AT, Oweis L, Ali M, Hamamy H
Clin Neurol Neurosurg 2023 Jul;230:107799. Epub 2023 May 22 doi: 10.1016/j.clineuro.2023.107799. PMID: 37236004
Sakakibara N, Nozu K, Yamamura T, Horinouchi T, Nagano C, Ye MJ, Ishiko S, Aoto Y, Rossanti R, Hamada R, Okamoto N, Shima Y, Nakanishi K, Matsuo M, Iijima K, Morisada N
J Hum Genet 2022 Jul;67(7):427-440. Epub 2022 Feb 9 doi: 10.1038/s10038-022-01020-5. PMID: 35140360
Taşkıran EZ, Karaosmanoğlu B, Koşukcu C, Ürel-Demir G, Akgün-Doğan Ö, Şimşek-Kiper PÖ, Alikaşifoğlu M, Boduroğlu K, Utine GE
J Intellect Disabil Res 2021 Jun;65(6):577-588. Epub 2021 Mar 19 doi: 10.1111/jir.12835. PMID: 33739554
Vogt G, El Choubassi N, Herczegfalvi Á, Kölbel H, Lekaj A, Schara U, Holtgrewe M, Krause S, Horvath R, Schuelke M, Hübner C, Mundlos S, Roos A, Lochmüller H, Karcagi V, Kornak U, Fischer-Zirnsak B
J Inherit Metab Dis 2021 Jul;44(4):972-986. Epub 2021 Feb 4 doi: 10.1002/jimd.12341. PMID: 33320377Free PMC Article
Coughlin CR 2nd, Tseng LA, Abdenur JE, Ashmore C, Boemer F, Bok LA, Boyer M, Buhas D, Clayton PT, Das A, Dekker H, Evangeliou A, Feillet F, Footitt EJ, Gospe SM Jr, Hartmann H, Kara M, Kristensen E, Lee J, Lilje R, Longo N, Lunsing RJ, Mills P, Papadopoulou MT, Pearl PL, Piazzon F, Plecko B, Saini AG, Santra S, Sjarif DR, Stockler-Ipsiroglu S, Striano P, Van Hove JLK, Verhoeven-Duif NM, Wijburg FA, Zuberi SM, van Karnebeek CDM
J Inherit Metab Dis 2021 Jan;44(1):178-192. Epub 2020 Dec 1 doi: 10.1002/jimd.12332. PMID: 33200442

Diagnosis

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
Masri AT, Oweis L, Ali M, Hamamy H
Clin Neurol Neurosurg 2023 Jul;230:107799. Epub 2023 May 22 doi: 10.1016/j.clineuro.2023.107799. PMID: 37236004
Taşkıran EZ, Karaosmanoğlu B, Koşukcu C, Ürel-Demir G, Akgün-Doğan Ö, Şimşek-Kiper PÖ, Alikaşifoğlu M, Boduroğlu K, Utine GE
J Intellect Disabil Res 2021 Jun;65(6):577-588. Epub 2021 Mar 19 doi: 10.1111/jir.12835. PMID: 33739554
Coughlin CR 2nd, Tseng LA, Abdenur JE, Ashmore C, Boemer F, Bok LA, Boyer M, Buhas D, Clayton PT, Das A, Dekker H, Evangeliou A, Feillet F, Footitt EJ, Gospe SM Jr, Hartmann H, Kara M, Kristensen E, Lee J, Lilje R, Longo N, Lunsing RJ, Mills P, Papadopoulou MT, Pearl PL, Piazzon F, Plecko B, Saini AG, Santra S, Sjarif DR, Stockler-Ipsiroglu S, Striano P, Van Hove JLK, Verhoeven-Duif NM, Wijburg FA, Zuberi SM, van Karnebeek CDM
J Inherit Metab Dis 2021 Jan;44(1):178-192. Epub 2020 Dec 1 doi: 10.1002/jimd.12332. PMID: 33200442
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

Therapy

Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
Coughlin CR 2nd, Tseng LA, Abdenur JE, Ashmore C, Boemer F, Bok LA, Boyer M, Buhas D, Clayton PT, Das A, Dekker H, Evangeliou A, Feillet F, Footitt EJ, Gospe SM Jr, Hartmann H, Kara M, Kristensen E, Lee J, Lilje R, Longo N, Lunsing RJ, Mills P, Papadopoulou MT, Pearl PL, Piazzon F, Plecko B, Saini AG, Santra S, Sjarif DR, Stockler-Ipsiroglu S, Striano P, Van Hove JLK, Verhoeven-Duif NM, Wijburg FA, Zuberi SM, van Karnebeek CDM
J Inherit Metab Dis 2021 Jan;44(1):178-192. Epub 2020 Dec 1 doi: 10.1002/jimd.12332. PMID: 33200442
Botta E, Offman J, Nardo T, Ricotti R, Zambruno G, Sansone D, Balestri P, Raams A, Kleijer WJ, Jaspers NG, Sarasin A, Lehmann AR, Stefanini M
Hum Mutat 2007 Jan;28(1):92-6. doi: 10.1002/humu.20419. PMID: 16977596

Prognosis

Buke B, Canverenler E, İpek G, Canverenler S, Akkaya H
J Med Ultrason (2001) 2017 Apr;44(2):197-202. Epub 2016 Oct 26 doi: 10.1007/s10396-016-0751-8. PMID: 27785575
Srinivasan J, Coleman L, Kornberg AJ
J Paediatr Child Health 2008 Jul-Aug;44(7-8):459-61. doi: 10.1111/j.1440-1754.2008.01340.x. PMID: 18638333
O'Dea D, Parfrey PS, Harnett JD, Hefferton D, Cramer BC, Green J
Am J Kidney Dis 1996 Jun;27(6):776-83. doi: 10.1016/s0272-6386(96)90513-2. PMID: 8651240
Maestri NE, Beaty TH
Am J Med Genet 1992 Nov 15;44(5):576-82. doi: 10.1002/ajmg.1320440509. PMID: 1481812
Mäenpää J
Arch Dis Child 1972 Dec;47(256):914-23. doi: 10.1136/adc.47.256.914. PMID: 4119068Free PMC Article

Clinical prediction guides

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
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
Hayakawa M, Matsubara T, Mochizuki Y, Takeuchi C, Minamitani M, Imai M, Kosaki K, Arai T, Murayama S
BMC Neurol 2022 Jan 3;22(1):2. doi: 10.1186/s12883-021-02514-z. PMID: 34979968Free PMC Article
Perez Y, Shorer Z, Liani-Leibson K, Chabosseau P, Kadir R, Volodarsky M, Halperin D, Barber-Zucker S, Shalev H, Schreiber R, Gradstein L, Gurevich E, Zarivach R, Rutter GA, Landau D, Birk OS
Brain 2017 Apr 1;140(4):928-939. doi: 10.1093/brain/awx013. PMID: 28334855Free PMC Article
Parvari R, Hershkovitz E, Grossman N, Gorodischer R, Loeys B, Zecic A, Mortier G, Gregory S, Sharony R, Kambouris M, Sakati N, Meyer BF, Al Aqeel AI, Al Humaidan AK, Al Zanhrani F, Al Swaid A, Al Othman J, Diaz GA, Weiner R, Khan KT, Gordon R, Gelb BD; HRD/Autosomal Recessive Kenny-Caffey Syndrome Consortium
Nat Genet 2002 Nov;32(3):448-52. Epub 2002 Oct 21 doi: 10.1038/ng1012. PMID: 12389028

Recent systematic reviews

Coughlin CR 2nd, Tseng LA, Abdenur JE, Ashmore C, Boemer F, Bok LA, Boyer M, Buhas D, Clayton PT, Das A, Dekker H, Evangeliou A, Feillet F, Footitt EJ, Gospe SM Jr, Hartmann H, Kara M, Kristensen E, Lee J, Lilje R, Longo N, Lunsing RJ, Mills P, Papadopoulou MT, Pearl PL, Piazzon F, Plecko B, Saini AG, Santra S, Sjarif DR, Stockler-Ipsiroglu S, Striano P, Van Hove JLK, Verhoeven-Duif NM, Wijburg FA, Zuberi SM, van Karnebeek CDM
J Inherit Metab Dis 2021 Jan;44(1):178-192. Epub 2020 Dec 1 doi: 10.1002/jimd.12332. PMID: 33200442

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