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Intellectual developmental disorder, autosomal recessive 68(MRT68)

MedGen UID:
1648490
Concept ID:
C4749033
Disease or Syndrome
Synonym: MENTAL RETARDATION, AUTOSOMAL RECESSIVE 68
 
Gene (location): TRMT1 (19p13.13)
 
Monarch Initiative: MONDO:0032665
OMIM®: 618302

Clinical features

From HPO
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.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Periventricular leukomalacia
MedGen UID:
6072
Concept ID:
C0023529
Disease or Syndrome
Periventricular leukomalacia is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia.
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.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
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.
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.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Broad eyebrow
MedGen UID:
344657
Concept ID:
C1856121
Finding
Regional increase in the width (height) of the eyebrow.
Narrow palpebral fissure
MedGen UID:
382506
Concept ID:
C2675021
Finding
Reduction in the vertical distance between the upper and lower eyelids.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.

Recent clinical studies

Etiology

Smogavec M, Cleall A, Hoyer J, Lederer D, Nassogne MC, Palmer EE, Deprez M, Benoit V, Maystadt I, Noakes C, Leal A, Shaw M, Gecz J, Raymond L, Reis A, Shears D, Brockmann K, Zweier C
J Med Genet 2016 Dec;53(12):820-827. Epub 2016 Jul 20 doi: 10.1136/jmedgenet-2016-103880. PMID: 27439707
Stevanin G, Paternotte C, Coutinho P, Klebe S, Elleuch N, Loureiro JL, Denis E, Cruz VT, Dürr A, Prud'homme JF, Weissenbach J, Brice A, Hazan J
Neurology 2007 May 22;68(21):1837-40. doi: 10.1212/01.wnl.0000262043.53386.22. PMID: 17515546
Zlotogora J
Am J Med Genet 1997 Feb 11;68(4):472-5. doi: 10.1002/(sici)1096-8628(19970211)68:4<472::aid-ajmg20>3.0.co;2-o. PMID: 9021024

Diagnosis

Köse E, Kasapkara ÇS, İnci A, Yıldız Y, Sürücü Kara İ, Kahraman AB, Tümer L, Dursun A, Eminoğlu FT
Eur J Med Genet 2024 Apr;68:104927. Epub 2024 Feb 19 doi: 10.1016/j.ejmg.2024.104927. PMID: 38382588
Alsemari A, Guzmán-Vega FJ, Meyer BF, Arold ST
Pediatr Neurol 2024 Feb;151:68-72. Epub 2023 Oct 19 doi: 10.1016/j.pediatrneurol.2023.10.005. PMID: 38113697
Indraneel KS, VRajalakshmi, Dayanandan Y, Reddy NM
J Assoc Physicians India 2023 Jan;71(1):1. PMID: 37116049
Smogavec M, Cleall A, Hoyer J, Lederer D, Nassogne MC, Palmer EE, Deprez M, Benoit V, Maystadt I, Noakes C, Leal A, Shaw M, Gecz J, Raymond L, Reis A, Shears D, Brockmann K, Zweier C
J Med Genet 2016 Dec;53(12):820-827. Epub 2016 Jul 20 doi: 10.1136/jmedgenet-2016-103880. PMID: 27439707
Moog U, van Mierlo I, van Schrojenstein Lantman-de Valk HM, Spaapen L, Maaskant MA, Curfs LM
Am J Med Genet C Semin Med Genet 2007 Aug 15;145C(3):293-301. doi: 10.1002/ajmg.c.30142. PMID: 17640047

Therapy

Mori T, Goji A, Toda Y, Ito H, Mori K, Kohmoto T, Imoto I, Kagami S
Brain Dev 2019 Nov;41(10):888-893. Epub 2019 Jul 25 doi: 10.1016/j.braindev.2019.07.005. PMID: 31353122

Prognosis

Phulpagar P, Holla VV, Tomar D, Kamble N, Yadav R, Pal PK, Muthusamy B
J Hum Genet 2023 Dec;68(12):859-866. Epub 2023 Sep 26 doi: 10.1038/s10038-023-01195-5. PMID: 37752213
Zou XH, Guo XX, Su HZ, Wang C, Dong EL, Wang N, Chen WJ, Zhang QJ
J Mol Neurosci 2019 Aug;68(4):640-646. Epub 2019 May 10 doi: 10.1007/s12031-019-01319-7. PMID: 31077085
Smogavec M, Cleall A, Hoyer J, Lederer D, Nassogne MC, Palmer EE, Deprez M, Benoit V, Maystadt I, Noakes C, Leal A, Shaw M, Gecz J, Raymond L, Reis A, Shears D, Brockmann K, Zweier C
J Med Genet 2016 Dec;53(12):820-827. Epub 2016 Jul 20 doi: 10.1136/jmedgenet-2016-103880. PMID: 27439707
Moog U, van Mierlo I, van Schrojenstein Lantman-de Valk HM, Spaapen L, Maaskant MA, Curfs LM
Am J Med Genet C Semin Med Genet 2007 Aug 15;145C(3):293-301. doi: 10.1002/ajmg.c.30142. PMID: 17640047

Clinical prediction guides

Khoddam S, Kamal N, Shiri A, Jafari Khamirani H, Manoochehri J, Dianatpour M, Tabei SMB, Dastgheib SA
Eur J Med Genet 2024 Apr;68:104928. Epub 2024 Feb 28 doi: 10.1016/j.ejmg.2024.104928. PMID: 38423277
Köse E, Kasapkara ÇS, İnci A, Yıldız Y, Sürücü Kara İ, Kahraman AB, Tümer L, Dursun A, Eminoğlu FT
Eur J Med Genet 2024 Apr;68:104927. Epub 2024 Feb 19 doi: 10.1016/j.ejmg.2024.104927. PMID: 38382588
Phulpagar P, Holla VV, Tomar D, Kamble N, Yadav R, Pal PK, Muthusamy B
J Hum Genet 2023 Dec;68(12):859-866. Epub 2023 Sep 26 doi: 10.1038/s10038-023-01195-5. PMID: 37752213
Smogavec M, Cleall A, Hoyer J, Lederer D, Nassogne MC, Palmer EE, Deprez M, Benoit V, Maystadt I, Noakes C, Leal A, Shaw M, Gecz J, Raymond L, Reis A, Shears D, Brockmann K, Zweier C
J Med Genet 2016 Dec;53(12):820-827. Epub 2016 Jul 20 doi: 10.1136/jmedgenet-2016-103880. PMID: 27439707
Shibasaki Y, Tanaka H, Iwabuchi K, Kawasaki S, Kondo H, Uekawa K, Ueda M, Kamiya T, Katayama Y, Nakamura A, Takashima H, Nakagawa M, Masuda M, Utsumi H, Nakamuro T, Tada K, Kurohara K, Inoue K, Koike F, Sakai T, Tsuji S, Kobayashi H
Ann Neurol 2000 Jul;48(1):108-12. PMID: 10894224

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