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Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities(DYTOABG)

MedGen UID:
934601
Concept ID:
C4310634
Disease or Syndrome
Synonyms: DYSTONIA 29, CHILDHOOD-ONSET; DYTOABG
SNOMED CT: MEPAN syndrome (1236805005); Mitochondrial enoyl coenzyme A reductase protein-associated neurodegeneration syndrome (1236805005); DYT29 - dystonia 29 (1236805005); Autosomal recessive childhood-onset dystonia DYT29 type (1236805005); Childhood-onset generalized dystonia, optic atrophy syndrome (1236805005)
 
Gene (location): MECR (1p35.3)
 
Monarch Initiative: MONDO:0015003
OMIM®: 617282
Orphanet: ORPHA508093

Disease characteristics

Excerpted from the GeneReview: MECR-Related Neurologic Disorder
MECR-related neurologic disorder is characterized by a progressive childhood-onset movement disorder and optic atrophy; intellect is often – but not always – preserved. The movement disorder typically presents between ages one and 6.5 years and is mainly dystonia that can be accompanied by chorea and/or ataxia. Over time some affected individuals require assistive devices for mobility. Speech fluency and intelligibility are progressively impaired due to dysarthria. Optic atrophy typically develops between ages four and 12 years and manifests as reduced visual acuity, which can include functional blindness (also known as legal blindness) in adulthood. Because only 13 affected individuals are known to the authors, and because nearly half of them were diagnosed retrospectively as adults, the natural history of disease progression and other aspects of the phenotype have not yet been completely defined. [from GeneReviews]
Authors:
Gali Heimer  |  Allison Gregory  |  Penelope Hogarth, et. al.   view full author information

Additional description

From OMIM
Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG) is an autosomal recessive neurologic disorder characterized by onset of involuntary movements in the first decade of life. Optic atrophy develops around the same time or slightly later. Severity is variable, and some patients lose independent ambulation. Brain imaging shows abnormalities in the basal ganglia. Cognition appears to be unaffected (summary by Heimer et al., 2016).  http://www.omim.org/entry/617282

Clinical features

From HPO
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.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Athetosis
MedGen UID:
2115
Concept ID:
C0004158
Disease or Syndrome
A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Clumsiness
MedGen UID:
66690
Concept ID:
C0233844
Sign or Symptom
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
Involuntary movements
MedGen UID:
140884
Concept ID:
C0427086
Sign or Symptom
Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Paroxysmal dyskinesia
MedGen UID:
156242
Concept ID:
C0752210
Disease or Syndrome
Episodic bouts of involuntary movements with dystonic, choreic, ballistic movements, or a combination thereof. There is no loss of consciousness during the attacks.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
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.
Craniofacial dystonia
MedGen UID:
868612
Concept ID:
C4023011
Disease or Syndrome
A form of focal dystonia affecting the face and especially the jaw that is induced by the act of speaking. It is an involuntary contraction of the masticatory muscles, resulting in dysarthria or dysphagia.
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.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Limb joint contracture
MedGen UID:
369611
Concept ID:
C1969879
Anatomical Abnormality
A contracture (chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin) that prevent normal movement of one or more joints of the limbs.
Blepharospasm
MedGen UID:
599
Concept ID:
C0005747
Disease or Syndrome
A focal dystonia that affects the muscles of the eyelids and brow, associated with involuntary recurrent spasm of both eyelids.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Esophoria
MedGen UID:
57753
Concept ID:
C0152216
Disease or Syndrome
A form of strabismus with both eyes turned inward to a relatively mild degree, usually defined as less than 10 prism diopters.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities

Recent clinical studies

Etiology

Liu Z, Shimura M, Zhang L, Zhang W, Wang J, Ogawa-Tominaga M, Wang J, Wang X, Lv J, Shi W, Zhang VW, Murayama K, Fang F
Mitochondrion 2021 Mar;57:222-229. Epub 2021 Jan 2 doi: 10.1016/j.mito.2020.12.014. PMID: 33401012
Gorukmez O, Gorukmez O, Havalı C
Neuropediatrics 2019 Oct;50(5):336-337. Epub 2019 May 28 doi: 10.1055/s-0039-1688767. PMID: 31137067
Darling A, Aguilera-Albesa S, Tello CA, Serrano M, Tomás M, Camino-León R, Fernández-Ramos J, Jiménez-Escrig A, Poó P, O'Callaghan M, Ortez C, Nascimento A, Fernández Mesaque RC, Madruga M, Arrabal L, Roldan S, Gómez-Martín H, Garrido C, Temudo T, Jou-Muñoz C, Muchart J, Huisman TAGM, Poretti A, Lupo V, Espinós C, Pérez-Dueñas B
Parkinsonism Relat Disord 2019 Apr;61:179-186. Epub 2018 Oct 13 doi: 10.1016/j.parkreldis.2018.10.013. PMID: 30340910
Heimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F; University of Washington Center for Mendelian Genomics, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ
Am J Hum Genet 2016 Dec 1;99(6):1229-1244. Epub 2016 Nov 3 doi: 10.1016/j.ajhg.2016.09.021. PMID: 27817865Free PMC Article
Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856

Diagnosis

Fiorini C, Degiorgi A, Cascavilla ML, Tropeano CV, La Morgia C, Battista M, Ormanbekova D, Palombo F, Carbonelli M, Bandello F, Carelli V, Maresca A, Barboni P, Baruffini E, Caporali L
J Med Genet 2023 Dec 21;61(1):93-101. doi: 10.1136/jmg-2023-109340. PMID: 37734847Free PMC Article
Liu Z, Shimura M, Zhang L, Zhang W, Wang J, Ogawa-Tominaga M, Wang J, Wang X, Lv J, Shi W, Zhang VW, Murayama K, Fang F
Mitochondrion 2021 Mar;57:222-229. Epub 2021 Jan 2 doi: 10.1016/j.mito.2020.12.014. PMID: 33401012
Gorukmez O, Gorukmez O, Havalı C
Neuropediatrics 2019 Oct;50(5):336-337. Epub 2019 May 28 doi: 10.1055/s-0039-1688767. PMID: 31137067
Coenen VA, Rijntjes M, Sajonz B, Piroth T, Prokop T, Jost W, Trippel M, Urbach H, Reinacher PC
J Neurol Surg A Cent Eur Neurosurg 2019 Jan;80(1):44-48. Epub 2018 Oct 5 doi: 10.1055/s-0038-1669472. PMID: 30290379
Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856

Therapy

Liu Z, Shimura M, Zhang L, Zhang W, Wang J, Ogawa-Tominaga M, Wang J, Wang X, Lv J, Shi W, Zhang VW, Murayama K, Fang F
Mitochondrion 2021 Mar;57:222-229. Epub 2021 Jan 2 doi: 10.1016/j.mito.2020.12.014. PMID: 33401012

Prognosis

Lacombe D, Van-Gils J, Lebrun M, Trimouille A, Michaud V, Cabet S, Chateil JF, Pedespan JM, Bar C, Lesca G
Brain Dev 2022 Sep;44(8):567-570. Epub 2022 May 24 doi: 10.1016/j.braindev.2022.05.001. PMID: 35623960
Darling A, Aguilera-Albesa S, Tello CA, Serrano M, Tomás M, Camino-León R, Fernández-Ramos J, Jiménez-Escrig A, Poó P, O'Callaghan M, Ortez C, Nascimento A, Fernández Mesaque RC, Madruga M, Arrabal L, Roldan S, Gómez-Martín H, Garrido C, Temudo T, Jou-Muñoz C, Muchart J, Huisman TAGM, Poretti A, Lupo V, Espinós C, Pérez-Dueñas B
Parkinsonism Relat Disord 2019 Apr;61:179-186. Epub 2018 Oct 13 doi: 10.1016/j.parkreldis.2018.10.013. PMID: 30340910
Coenen VA, Rijntjes M, Sajonz B, Piroth T, Prokop T, Jost W, Trippel M, Urbach H, Reinacher PC
J Neurol Surg A Cent Eur Neurosurg 2019 Jan;80(1):44-48. Epub 2018 Oct 5 doi: 10.1055/s-0038-1669472. PMID: 30290379
Heimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F; University of Washington Center for Mendelian Genomics, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ
Am J Hum Genet 2016 Dec 1;99(6):1229-1244. Epub 2016 Nov 3 doi: 10.1016/j.ajhg.2016.09.021. PMID: 27817865Free PMC Article
Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856

Clinical prediction guides

Lacombe D, Van-Gils J, Lebrun M, Trimouille A, Michaud V, Cabet S, Chateil JF, Pedespan JM, Bar C, Lesca G
Brain Dev 2022 Sep;44(8):567-570. Epub 2022 May 24 doi: 10.1016/j.braindev.2022.05.001. PMID: 35623960
Liu Z, Shimura M, Zhang L, Zhang W, Wang J, Ogawa-Tominaga M, Wang J, Wang X, Lv J, Shi W, Zhang VW, Murayama K, Fang F
Mitochondrion 2021 Mar;57:222-229. Epub 2021 Jan 2 doi: 10.1016/j.mito.2020.12.014. PMID: 33401012
Darling A, Aguilera-Albesa S, Tello CA, Serrano M, Tomás M, Camino-León R, Fernández-Ramos J, Jiménez-Escrig A, Poó P, O'Callaghan M, Ortez C, Nascimento A, Fernández Mesaque RC, Madruga M, Arrabal L, Roldan S, Gómez-Martín H, Garrido C, Temudo T, Jou-Muñoz C, Muchart J, Huisman TAGM, Poretti A, Lupo V, Espinós C, Pérez-Dueñas B
Parkinsonism Relat Disord 2019 Apr;61:179-186. Epub 2018 Oct 13 doi: 10.1016/j.parkreldis.2018.10.013. PMID: 30340910
Heimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F; University of Washington Center for Mendelian Genomics, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ
Am J Hum Genet 2016 Dec 1;99(6):1229-1244. Epub 2016 Nov 3 doi: 10.1016/j.ajhg.2016.09.021. PMID: 27817865Free PMC Article
Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856

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