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Intellectual disability, autosomal dominant 39(MRD39)

MedGen UID:
909304
Concept ID:
C4225296
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 39; Mental retardation, autosomal dominant 39; MRD39
 
Gene (location): MYT1L (2p25.3)
 
Monarch Initiative: MONDO:0014678
OMIM®: 616521

Definition

An autosomal dominant condition caused by mutation(s) in the MYT1L gene, encoding myelin transcription factor 1-like protein. It is characterized by intellectual disability and mild dysmorphic facial features. [from NCI]

Clinical features

From HPO
Bilateral talipes equinovarus
MedGen UID:
332956
Concept ID:
C1837835
Congenital Abnormality
Bilateral clubfoot deformity.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
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).
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.
Polyphagia
MedGen UID:
9369
Concept ID:
C0020505
Finding
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Self-mutilation
MedGen UID:
19925
Concept ID:
C0036601
Injury or Poisoning
Deliberate harm to one's body resulting in tissue damage, without a conscious intent to die.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
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.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
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\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\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.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
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.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Abnormal blood glucose concentration
MedGen UID:
869175
Concept ID:
C4023597
Finding
An abnormality of the concentration of glucose in the blood.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Wide nasal base
MedGen UID:
341506
Concept ID:
C1849667
Finding
Increased distance between the attachments of the alae nasi to the face.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Increased circulating cortisol level
MedGen UID:
871175
Concept ID:
C4025651
Finding
Overproduction of the hormone of cortisol by the adrenal cortex, resulting in a characteristic combination of clinical symptoms termed Cushing syndrome, with truncal obesity, a round, full face, striae atrophicae and acne, muscle weakness, and other features.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVIntellectual disability, autosomal dominant 39

Recent clinical studies

Etiology

Dolu MH, Öz Tunçer G, Akça Ü, Aydın S, Bahadir O, Sezer Ö, Aksoy A, Taşdemir HA
J Child Neurol 2024 Jun;39(7-8):260-267. Epub 2024 Jul 25 doi: 10.1177/08830738241263243. PMID: 39051604
Pavinato L, Villamor-Payà M, Sanchiz-Calvo M, Andreoli C, Gay M, Vilaseca M, Arauz-Garofalo G, Ciolfi A, Bruselles A, Pippucci T, Prota V, Carli D, Giorgio E, Radio FC, Antona V, Giuffrè M, Ranguin K, Colson C, De Rubeis S, Dimartino P, Buxbaum JD, Ferrero GB, Tartaglia M, Martinelli S, Stracker TH, Brusco A
J Med Genet 2022 Feb;59(2):170-179. Epub 2020 Dec 15 doi: 10.1136/jmedgenet-2020-107281. PMID: 33323470Free PMC Article
Al Tuwaijri A, Alfadhel M
J Pediatr Endocrinol Metab 2019 Apr 24;32(4):409-413. doi: 10.1515/jpem-2018-0505. PMID: 30796847
López M, Seidel V, Santibáñez P, Cervera-Acedo C, Castro-de Castro P, Domínguez-Garrido E
BMC Med Genet 2016 Dec 13;17(1):97. doi: 10.1186/s12881-016-0361-8. PMID: 27964710Free PMC Article
Bounakis N, Karampalis C, Sharp H, Tsirikos AI
J Med Case Rep 2015 Jan 18;9:10. doi: 10.1186/1752-1947-9-10. PMID: 25596810Free PMC Article

Diagnosis

Dolu MH, Öz Tunçer G, Akça Ü, Aydın S, Bahadir O, Sezer Ö, Aksoy A, Taşdemir HA
J Child Neurol 2024 Jun;39(7-8):260-267. Epub 2024 Jul 25 doi: 10.1177/08830738241263243. PMID: 39051604
Zhao A, Zhou R, Gu Q, Liu M, Zhang B, Huang J, Yang B, Yao R, Wang J, Lv H, Wang J, Shen Y, Wang H, Chen X
Clin Chim Acta 2021 Dec;523:10-18. Epub 2021 Aug 31 doi: 10.1016/j.cca.2021.08.030. PMID: 34478686
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
Elhamouly Y, Dowidar KM
Spec Care Dentist 2019 Mar;39(2):236-240. Epub 2019 Feb 5 doi: 10.1111/scd.12364. PMID: 30720215
Robert A, Leroy V, Riquet A, Gogneaux L, Boutry N, Avni FE
Radiol Med 2016 May;121(5):402-8. Epub 2015 Jul 29 doi: 10.1007/s11547-015-0572-7. PMID: 26219723

Prognosis

Dolu MH, Öz Tunçer G, Akça Ü, Aydın S, Bahadir O, Sezer Ö, Aksoy A, Taşdemir HA
J Child Neurol 2024 Jun;39(7-8):260-267. Epub 2024 Jul 25 doi: 10.1177/08830738241263243. PMID: 39051604
Al Tuwaijri A, Alfadhel M
J Pediatr Endocrinol Metab 2019 Apr 24;32(4):409-413. doi: 10.1515/jpem-2018-0505. PMID: 30796847
Ruaud L, Rice GI, Cabrol C, Piard J, Rodero M, van Eyk L, Boucher-Brischoux E, de Noordhout AM, Maré R, Scalais E, Pauly F, Debray FG, Dobyns W, Uggenti C, Park JW, Hur S, Livingston JH, Crow YJ, Van Maldergem L
Hum Mutat 2018 Aug;39(8):1076-1080. Epub 2018 Jun 4 doi: 10.1002/humu.23554. PMID: 29782060Free PMC Article
Hamilton MJ, Newbury-Ecob R, Holder-Espinasse M, Yau S, Lillis S, Hurst JA, Clement E, Reardon W, Joss S, Hobson E, Blyth M, Al-Shehhi M, Lynch SA, Suri M; DDD Study
Clin Dysmorphol 2016 Oct;25(4):135-45. doi: 10.1097/MCD.0000000000000143. PMID: 27465822
Bounakis N, Karampalis C, Sharp H, Tsirikos AI
J Med Case Rep 2015 Jan 18;9:10. doi: 10.1186/1752-1947-9-10. PMID: 25596810Free PMC Article

Clinical prediction guides

Zhao A, Zhou R, Gu Q, Liu M, Zhang B, Huang J, Yang B, Yao R, Wang J, Lv H, Wang J, Shen Y, Wang H, Chen X
Clin Chim Acta 2021 Dec;523:10-18. Epub 2021 Aug 31 doi: 10.1016/j.cca.2021.08.030. PMID: 34478686
Elhamouly Y, Dowidar KM
Spec Care Dentist 2019 Mar;39(2):236-240. Epub 2019 Feb 5 doi: 10.1111/scd.12364. PMID: 30720215
Ruaud L, Rice GI, Cabrol C, Piard J, Rodero M, van Eyk L, Boucher-Brischoux E, de Noordhout AM, Maré R, Scalais E, Pauly F, Debray FG, Dobyns W, Uggenti C, Park JW, Hur S, Livingston JH, Crow YJ, Van Maldergem L
Hum Mutat 2018 Aug;39(8):1076-1080. Epub 2018 Jun 4 doi: 10.1002/humu.23554. PMID: 29782060Free PMC Article
Hamilton MJ, Newbury-Ecob R, Holder-Espinasse M, Yau S, Lillis S, Hurst JA, Clement E, Reardon W, Joss S, Hobson E, Blyth M, Al-Shehhi M, Lynch SA, Suri M; DDD Study
Clin Dysmorphol 2016 Oct;25(4):135-45. doi: 10.1097/MCD.0000000000000143. PMID: 27465822

Recent systematic reviews

Xin C, Wang C, Wang Y, Zhao J, Wang L, Li R, Liu J
BMC Med Genet 2018 Feb 27;19(1):31. doi: 10.1186/s12881-018-0545-5. PMID: 29482518Free PMC Article

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