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Intellectual disability, autosomal recessive 27(MRT27)

MedGen UID:
482168
Concept ID:
C3280538
Disease or Syndrome
Synonyms: Intellectual developmental disorder, autosomal recessive 27; Mental retardation, autosomal recessive 27; MRT27
 
Gene (location): LINS1 (15q26.3)
 
Monarch Initiative: MONDO:0013702
OMIM®: 614340

Definition

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the LINS1 gene. [from MONDO]

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
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.
Persistent head lag
MedGen UID:
256151
Concept ID:
C1141883
Finding
The Premie-Neuro and the Dubowitz Neurological Examination score head lag in the same manner. Scoring for both is as follows
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.
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
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.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.

Professional guidelines

PubMed

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
Dimopoulou A, Fischer B, Gardeitchik T, Schröter P, Kayserili H, Schlack C, Li Y, Brum JM, Barisic I, Castori M, Spaich C, Fletcher E, Mahayri Z, Bhat M, Girisha KM, Lachlan K, Johnson D, Phadke S, Gupta N, Simandlova M, Kabra M, David A, Nijtmans L, Chitayat D, Tuysuz B, Brancati F, Mundlos S, Van Maldergem L, Morava E, Wollnik B, Kornak U
Mol Genet Metab 2013 Nov;110(3):352-61. Epub 2013 Aug 24 doi: 10.1016/j.ymgme.2013.08.009. PMID: 24035636

Recent clinical studies

Etiology

Bukowska-Olech E, Glista F, Dinwiddie A, Pepler A, Jamsheer A
Eur J Med Genet 2023 Jan;66(1):104668. Epub 2022 Nov 13 doi: 10.1016/j.ejmg.2022.104668. PMID: 36384198
Chelban V, Alsagob M, Kloth K, Chirita-Emandi A, Vandrovcova J, Maroofian R, Davagnanam I, Bakhtiari S, AlSayed MD, Rahbeeni Z, AlZaidan H, Malintan NT, Johannsen J, Efthymiou S, Ghayoor Karimiani E, Mankad K, Al-Shahrani SA, Beiraghi Toosi M, AlShammari M, Groppa S, Haridy NA, AlQuait L, Qari A, Huma R, Salih MA, Almass R, Almutairi FB, Hamad MH, Alorainy IA, Ramzan K, Imtiaz F, Puiu M, Kruer MC, Bierhals T, Wood NW, Colak D, Houlden H, Kaya N
Eur J Neurol 2020 Feb;27(2):334-342. Epub 2019 Oct 17 doi: 10.1111/ene.14082. PMID: 31509304Free PMC Article
Chemin J, Siquier-Pernet K, Nicouleau M, Barcia G, Ahmad A, Medina-Cano D, Hanein S, Altin N, Hubert L, Bole-Feysot C, Fourage C, Nitschké P, Thevenon J, Rio M, Blanc P, Vidal C, Bahi-Buisson N, Desguerre I, Munnich A, Lyonnet S, Boddaert N, Fassi E, Shinawi M, Zimmerman H, Amiel J, Faivre L, Colleaux L, Lory P, Cantagrel V
Brain 2018 Jul 1;141(7):1998-2013. doi: 10.1093/brain/awy145. PMID: 29878067
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
Castori M, Valiante M, Pascolini G, Leuzzi V, Pizzuti A, Grammatico P
Eur J Med Genet 2013 Oct;56(10):570-6. Epub 2013 Aug 27 doi: 10.1016/j.ejmg.2013.08.004. PMID: 23994350

Diagnosis

Hsu RH, Lee CH, Chien YH, Lin SP, Hung MZ, Chen NC, Lin YL, Hwu WL, Lee NC
Mol Genet Genomic Med 2023 Jun;11(6):e2160. Epub 2023 Feb 27 doi: 10.1002/mgg3.2160. PMID: 36849876Free PMC Article
Järvelä I, Määttä T, Acharya A, Leppälä J, Jhangiani SN, Arvio M, Siren A, Kankuri-Tammilehto M, Kokkonen H, Palomäki M, Varilo T, Fang M, Hadley TD, Jolly A, Linnankivi T, Paetau R, Saarela A, Kälviäinen R, Olme J, Nouel-Saied LM, Cornejo-Sanchez DM, Llaci L, Lupski JR, Posey JE, Leal SM, Schrauwen I
Hum Genet 2021 Jul;140(7):1011-1029. Epub 2021 Mar 12 doi: 10.1007/s00439-021-02268-1. PMID: 33710394Free PMC Article
Chelban V, Alsagob M, Kloth K, Chirita-Emandi A, Vandrovcova J, Maroofian R, Davagnanam I, Bakhtiari S, AlSayed MD, Rahbeeni Z, AlZaidan H, Malintan NT, Johannsen J, Efthymiou S, Ghayoor Karimiani E, Mankad K, Al-Shahrani SA, Beiraghi Toosi M, AlShammari M, Groppa S, Haridy NA, AlQuait L, Qari A, Huma R, Salih MA, Almass R, Almutairi FB, Hamad MH, Alorainy IA, Ramzan K, Imtiaz F, Puiu M, Kruer MC, Bierhals T, Wood NW, Colak D, Houlden H, Kaya N
Eur J Neurol 2020 Feb;27(2):334-342. Epub 2019 Oct 17 doi: 10.1111/ene.14082. PMID: 31509304Free PMC Article
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
Dimopoulou A, Fischer B, Gardeitchik T, Schröter P, Kayserili H, Schlack C, Li Y, Brum JM, Barisic I, Castori M, Spaich C, Fletcher E, Mahayri Z, Bhat M, Girisha KM, Lachlan K, Johnson D, Phadke S, Gupta N, Simandlova M, Kabra M, David A, Nijtmans L, Chitayat D, Tuysuz B, Brancati F, Mundlos S, Van Maldergem L, Morava E, Wollnik B, Kornak U
Mol Genet Metab 2013 Nov;110(3):352-61. Epub 2013 Aug 24 doi: 10.1016/j.ymgme.2013.08.009. PMID: 24035636

Therapy

Koyama S, Okabe Y, Suzuki Y, Igari R, Sato H, Iseki C, Tanji K, Suzuki K, Ohta Y
BMC Neurol 2022 May 25;22(1):193. doi: 10.1186/s12883-022-02711-4. PMID: 35614401Free PMC Article
Okur V, Cho MT, van Wijk R, van Oirschot B, Picker J, Coury SA, Grange D, Manwaring L, Krantz I, Muraresku CC, Hulick PJ, May H, Pierce E, Place E, Bujakowska K, Telegrafi A, Douglas G, Monaghan KG, Begtrup A, Wilson A, Retterer K, Anyane-Yeboa K, Chung WK
Eur J Hum Genet 2019 Jul;27(7):1081-1089. Epub 2019 Feb 18 doi: 10.1038/s41431-019-0366-9. PMID: 30778173Free PMC Article
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
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
Suh S, Kim HK, Park HD, Ki CS, Kim MY, Jin SM, Kim SW, Hur KY, Kim KW, Kim JH
Eur J Med Genet 2012 Jan;55(1):71-4. Epub 2011 Sep 16 doi: 10.1016/j.ejmg.2011.08.003. PMID: 21958693

Prognosis

Saffari A, Lau T, Tajsharghi H, Karimiani EG, Kariminejad A, Efthymiou S, Zifarelli G, Sultan T, Toosi MB, Sedighzadeh S, Siu VM, Ortigoza-Escobar JD, AlShamsi AM, Ibrahim S, Al-Sannaa NA, Al-Hertani W, Sandra W, Tarnopolsky M, Alavi S, Li C, Day-Salvatore DL, Martínez-González MJ, Levandoski KM, Bedoukian E, Madan-Khetarpal S, Idleburg MJ, Menezes MJ, Siddharth A, Platzer K, Oppermann H, Smitka M, Collins F, Lek M, Shahrooei M, Ghavideldarestani M, Herman I, Rendu J, Faure J, Baker J, Bhambhani V, Calderwood L, Akhondian J, Imannezhad S, Mirzadeh HS, Hashemi N, Doosti M, Safi M, Ahangari N, Torbati PN, Abedini S, Salpietro V, Gulec EY, Eshaghian S, Ghazavi M, Pascher MT, Vogel M, Abicht A, Moutton S, Bruel AL, Rieubland C, Gallati S, Strom TM, Lochmüller H, Mohammadi MH, Alvi JR, Zackai EH, Keena BA, Skraban CM, Berger SI, Andrew EH, Rahimian E, Morrow MM, Wentzensen IM, Millan F, Henderson LB, Dafsari HS, Jungbluth H, Gomez-Ospina N, McRae A, Peter M, Veltra D, Marinakis NM, Sofocleous C, Ashrafzadeh F, Pehlivan D, Lemke JR, Melki J, Benezit A, Bauer P, Weis D, Lupski JR, Senderek J, Christodoulou J, Chung WK, Goodchild R, Offiah AC, Moreno-De-Luca A, Suri M, Ebrahimi-Fakhari D, Houlden H, Maroofian R
Brain 2023 Aug 1;146(8):3273-3288. doi: 10.1093/brain/awad039. PMID: 36757831Free PMC Article
Chelban V, Alsagob M, Kloth K, Chirita-Emandi A, Vandrovcova J, Maroofian R, Davagnanam I, Bakhtiari S, AlSayed MD, Rahbeeni Z, AlZaidan H, Malintan NT, Johannsen J, Efthymiou S, Ghayoor Karimiani E, Mankad K, Al-Shahrani SA, Beiraghi Toosi M, AlShammari M, Groppa S, Haridy NA, AlQuait L, Qari A, Huma R, Salih MA, Almass R, Almutairi FB, Hamad MH, Alorainy IA, Ramzan K, Imtiaz F, Puiu M, Kruer MC, Bierhals T, Wood NW, Colak D, Houlden H, Kaya N
Eur J Neurol 2020 Feb;27(2):334-342. Epub 2019 Oct 17 doi: 10.1111/ene.14082. PMID: 31509304Free PMC Article
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
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
Dimopoulou A, Fischer B, Gardeitchik T, Schröter P, Kayserili H, Schlack C, Li Y, Brum JM, Barisic I, Castori M, Spaich C, Fletcher E, Mahayri Z, Bhat M, Girisha KM, Lachlan K, Johnson D, Phadke S, Gupta N, Simandlova M, Kabra M, David A, Nijtmans L, Chitayat D, Tuysuz B, Brancati F, Mundlos S, Van Maldergem L, Morava E, Wollnik B, Kornak U
Mol Genet Metab 2013 Nov;110(3):352-61. Epub 2013 Aug 24 doi: 10.1016/j.ymgme.2013.08.009. PMID: 24035636

Clinical prediction guides

Saffari A, Lau T, Tajsharghi H, Karimiani EG, Kariminejad A, Efthymiou S, Zifarelli G, Sultan T, Toosi MB, Sedighzadeh S, Siu VM, Ortigoza-Escobar JD, AlShamsi AM, Ibrahim S, Al-Sannaa NA, Al-Hertani W, Sandra W, Tarnopolsky M, Alavi S, Li C, Day-Salvatore DL, Martínez-González MJ, Levandoski KM, Bedoukian E, Madan-Khetarpal S, Idleburg MJ, Menezes MJ, Siddharth A, Platzer K, Oppermann H, Smitka M, Collins F, Lek M, Shahrooei M, Ghavideldarestani M, Herman I, Rendu J, Faure J, Baker J, Bhambhani V, Calderwood L, Akhondian J, Imannezhad S, Mirzadeh HS, Hashemi N, Doosti M, Safi M, Ahangari N, Torbati PN, Abedini S, Salpietro V, Gulec EY, Eshaghian S, Ghazavi M, Pascher MT, Vogel M, Abicht A, Moutton S, Bruel AL, Rieubland C, Gallati S, Strom TM, Lochmüller H, Mohammadi MH, Alvi JR, Zackai EH, Keena BA, Skraban CM, Berger SI, Andrew EH, Rahimian E, Morrow MM, Wentzensen IM, Millan F, Henderson LB, Dafsari HS, Jungbluth H, Gomez-Ospina N, McRae A, Peter M, Veltra D, Marinakis NM, Sofocleous C, Ashrafzadeh F, Pehlivan D, Lemke JR, Melki J, Benezit A, Bauer P, Weis D, Lupski JR, Senderek J, Christodoulou J, Chung WK, Goodchild R, Offiah AC, Moreno-De-Luca A, Suri M, Ebrahimi-Fakhari D, Houlden H, Maroofian R
Brain 2023 Aug 1;146(8):3273-3288. doi: 10.1093/brain/awad039. PMID: 36757831Free PMC Article
Dolgin V, Straussberg R, Xu R, Mileva I, Yogev Y, Khoury R, Konen O, Barhum Y, Zvulunov A, Mao C, Birk OS
Eur J Hum Genet 2019 Nov;27(11):1668-1676. Epub 2019 Jun 11 doi: 10.1038/s41431-019-0444-z. PMID: 31186544Free PMC Article
Ansar M, Ullah F, Paracha SA, Adams DJ, Lai A, Pais L, Iwaszkiewicz J, Millan F, Sarwar MT, Agha Z, Shah SF, Qaisar AA, Falconnet E, Zoete V, Ranza E, Makrythanasis P, Santoni FA, Ahmed J, Katsanis N, Walsh C, Davis EE, Antonarakis SE
Am J Hum Genet 2019 Jun 6;104(6):1073-1087. Epub 2019 May 9 doi: 10.1016/j.ajhg.2019.04.002. PMID: 31079899Free PMC Article
Goto M, Okada M, Komaki H, Sugai K, Sasaki M, Noguchi S, Nonaka I, Nishino I, Hayashi YK
Orphanet J Rare Dis 2014 Apr 23;9:58. doi: 10.1186/1750-1172-9-58. PMID: 24755310Free PMC Article
Castori M, Valiante M, Pascolini G, Leuzzi V, Pizzuti A, Grammatico P
Eur J Med Genet 2013 Oct;56(10):570-6. Epub 2013 Aug 27 doi: 10.1016/j.ejmg.2013.08.004. PMID: 23994350

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