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Intellectual disability, autosomal recessive 54(MRT54)

MedGen UID:
934722
Concept ID:
C4310755
Disease or Syndrome
Synonym: MRT54
 
Gene (location): TNIK (3q26.2-26.31)
 
Monarch Initiative: MONDO:0014876
OMIM®: 617028

Definition

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

Clinical features

From HPO
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
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.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
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.

Professional guidelines

PubMed

Lin L, Zhang Y, Pan H, Wang J, Qi Y, Ma Y
Orphanet J Rare Dis 2020 Nov 11;15(1):317. doi: 10.1186/s13023-020-01599-y. PMID: 33176815Free PMC Article

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
Lin L, Zhang Y, Pan H, Wang J, Qi Y, Ma Y
Orphanet J Rare Dis 2020 Nov 11;15(1):317. doi: 10.1186/s13023-020-01599-y. PMID: 33176815Free PMC Article
Schossig A, Bloch-Zupan A, Lussi A, Wolf NI, Raskin S, Cohen M, Giuliano F, Jurgens J, Krabichler B, Koolen DA, de Macena Sobreira NL, Maurer E, Muller-Bolla M, Penzien J, Zschocke J, Kapferer-Seebacher I
J Med Genet 2017 Jan;54(1):54-62. Epub 2016 Sep 6 doi: 10.1136/jmedgenet-2016-103988. PMID: 27600704
Laxova R, Ridler MA, Bowen-Bravery M
Am J Med Genet 1977;1(1):75-86. doi: 10.1002/ajmg.1320010109. PMID: 147626
Matalon R, Dorfman A
J Clin Invest 1974 Oct;54(4):907-12. doi: 10.1172/JCI107830. PMID: 4214836Free PMC Article

Diagnosis

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
Muzammal M, Ahmad S, Ali MZ, Khan MA
Ann Hum Genet 2021 Sep;85(5):147-154. Epub 2021 Apr 21 doi: 10.1111/ahg.12425. PMID: 33881165
Lin L, Zhang Y, Pan H, Wang J, Qi Y, Ma Y
Orphanet J Rare Dis 2020 Nov 11;15(1):317. doi: 10.1186/s13023-020-01599-y. PMID: 33176815Free PMC Article
Schossig A, Bloch-Zupan A, Lussi A, Wolf NI, Raskin S, Cohen M, Giuliano F, Jurgens J, Krabichler B, Koolen DA, de Macena Sobreira NL, Maurer E, Muller-Bolla M, Penzien J, Zschocke J, Kapferer-Seebacher I
J Med Genet 2017 Jan;54(1):54-62. Epub 2016 Sep 6 doi: 10.1136/jmedgenet-2016-103988. PMID: 27600704
Srinath A, Shneider BL
J Pediatr Gastroenterol Nutr 2012 May;54(5):580-7. doi: 10.1097/MPG.0b013e31824711b7. PMID: 22197937Free PMC Article

Therapy

Schossig A, Bloch-Zupan A, Lussi A, Wolf NI, Raskin S, Cohen M, Giuliano F, Jurgens J, Krabichler B, Koolen DA, de Macena Sobreira NL, Maurer E, Muller-Bolla M, Penzien J, Zschocke J, Kapferer-Seebacher I
J Med Genet 2017 Jan;54(1):54-62. Epub 2016 Sep 6 doi: 10.1136/jmedgenet-2016-103988. PMID: 27600704

Prognosis

Muzammal M, Ahmad S, Ali MZ, Khan MA
Ann Hum Genet 2021 Sep;85(5):147-154. Epub 2021 Apr 21 doi: 10.1111/ahg.12425. PMID: 33881165
Lin L, Zhang Y, Pan H, Wang J, Qi Y, Ma Y
Orphanet J Rare Dis 2020 Nov 11;15(1):317. doi: 10.1186/s13023-020-01599-y. PMID: 33176815Free PMC Article
Ben-Salem S, Gleeson JG, Al-Shamsi AM, Islam B, Hertecant J, Ali BR, Al-Gazali L
Metab Brain Dis 2015 Jun;30(3):687-94. Epub 2014 Sep 17 doi: 10.1007/s11011-014-9618-0. PMID: 25227173Free PMC Article

Clinical prediction guides

Muzammal M, Ahmad S, Ali MZ, Khan MA
Ann Hum Genet 2021 Sep;85(5):147-154. Epub 2021 Apr 21 doi: 10.1111/ahg.12425. PMID: 33881165
Ben-Salem S, Gleeson JG, Al-Shamsi AM, Islam B, Hertecant J, Ali BR, Al-Gazali L
Metab Brain Dis 2015 Jun;30(3):687-94. Epub 2014 Sep 17 doi: 10.1007/s11011-014-9618-0. PMID: 25227173Free PMC Article
Oehl-Jaschkowitz B, Vanakker OM, De Paepe A, Menten B, Martin T, Weber G, Christmann A, Krier R, Scheid S, McNerlan SE, McKee S, Tzschach A
Am J Med Genet A 2014 Mar;164A(3):620-6. Epub 2013 Dec 19 doi: 10.1002/ajmg.a.36321. PMID: 24357125
Schuurs-Hoeijmakers JH, Hehir-Kwa JY, Pfundt R, van Bon BW, de Leeuw N, Kleefstra T, Willemsen MA, van Kessel AG, Brunner HG, Veltman JA, van Bokhoven H, de Brouwer AP, de Vries BB
Eur J Hum Genet 2011 May;19(5):597-601. Epub 2011 Jan 19 doi: 10.1038/ejhg.2010.167. PMID: 21248743Free PMC Article

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