U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Infantile onset spinocerebellar ataxia(MTDPS7)

MedGen UID:
338613
Concept ID:
C1849096
Disease or Syndrome
Synonyms: Mitochondrial DNA depletion syndrome 7 (hepatocerebral type); MTDPS7; Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis; OPHTHALMOPLEGIA, HYPOTONIA, ATAXIA, HYPOACUSIS, AND ATHETOSIS; SCA8 (formerly); Spinocerebellar ataxia 8 (formerly); Spinocerebellar ataxia infantile with sensory neuropathy
SNOMED CT: Infantile onset spinocerebellar ataxia (724227000); Ohaha syndrome (724227000); Ophthalmoplegia, hypotonia, ataxia, hypoacusis, athetosis syndrome (724227000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): TWNK (10q24.31)
 
Monarch Initiative: MONDO:0010060
OMIM®: 271245
Orphanet: ORPHA1186

Definition

Infantile-onset spinocerebellar ataxia (IOSCA) is a severe, progressive neurodegenerative disorder characterized by normal development until age one year, followed by onset of ataxia, muscle hypotonia, loss of deep-tendon reflexes, and athetosis. Ophthalmoplegia and sensorineural deafness develop by age seven years. By adolescence, affected individuals are profoundly deaf and no longer ambulatory; sensory axonal neuropathy, optic atrophy, autonomic nervous system dysfunction, and hypergonadotropic hypogonadism in females become evident. Epilepsy can develop into a serious and often fatal encephalopathy: myoclonic jerks or focal clonic seizures that progress to epilepsia partialis continua followed by status epilepticus with loss of consciousness. [from GeneReviews]

Additional descriptions

From OMIM
Mitochondrial DNA depletion syndrome-7 is an autosomal recessive severe neurodegenerative disorder characterized primarily by hypotonia, ataxia, ophthalmoplegia, hearing loss, seizures, and sensory axonal neuropathy. Although originally classified as a form of spinocerebellar ataxia (see, e.g., SCA1, 164400) (Koskinen et al., 1994), it has been reclassified as a mitochondrial DNA depletion syndrome (Hakonen et al., 2008) based on the finding of mtDNA depletion in the brain and liver of affected individuals. For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041).  http://www.omim.org/entry/271245
From MedlinePlus Genetics
Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance.

People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation.

IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness.

Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy).

Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5.  https://medlineplus.gov/genetics/condition/infantile-onset-spinocerebellar-ataxia

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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).
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
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.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Epilepsia partialis continua
MedGen UID:
39303
Concept ID:
C0085543
Disease or Syndrome
Epilepsia partialis continua (also called Kojevnikov's or Kozhevnikov's epilepsia) is a type of focal motor status epilepticus characterized by repeated stereotyped simple motor manifestations such as jerks, typically of a limb or the face, recurring every few seconds or minutes for extended periods (days or years).
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Migraine
MedGen UID:
57451
Concept ID:
C0149931
Disease or Syndrome
Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms.
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.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
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.
Epileptic encephalopathy
MedGen UID:
452596
Concept ID:
C0543888
Disease or Syndrome
A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death.
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.
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Sensory axonal neuropathy
MedGen UID:
334116
Concept ID:
C1842587
Finding
An axonal neuropathy of peripheral sensory nerves.
Decreased number of large peripheral myelinated nerve fibers
MedGen UID:
395303
Concept ID:
C1859606
Finding
A reduced number of large myelinated nerve fibers.
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.
Cerebellar cortical atrophy
MedGen UID:
870270
Concept ID:
C4024710
Disease or Syndrome
Atrophy (wasting) of the cerebellar cortex.
Atrophy/Degeneration affecting the brainstem
MedGen UID:
870454
Concept ID:
C4024900
Disease or Syndrome
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Excessive daytime somnolence
MedGen UID:
1635612
Concept ID:
C4551761
Sign or Symptom
A state of abnormally strong desire for sleep during the daytime.
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.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Fiber type grouping
MedGen UID:
478824
Concept ID:
C3277194
Finding
An abnormal distribution of muscle fiber types in muscle tissue. Human skeletal muscle contains at least two fiber types recognizable by histochemical techniques. In transverse sections of normal skeletal muscle, type 1 and type 2 fibers are distributed in a random fashion. Grouping of fibers of the same type can be seen in certain peripheral neuropathies, thought to be due to reinnervation of denervated muscle fibers by sprouting axons. With grouping, motor units enlarge. The fibers of a motor unit, which are normally scattered, come to lie adjacent to one another. Histochemical examination shows groups of muscle fibers of the same histochemical type.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
An abnormally high concentration in the circulation of aspartate aminotransferase (AST).
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Hypergonadotropic hypogonadism
MedGen UID:
184926
Concept ID:
C0948896
Disease or Syndrome
Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay.
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.
Ophthalmoplegia
MedGen UID:
45205
Concept ID:
C0029089
Sign or Symptom
Paralysis of one or more extraocular muscles that are responsible for eye movements.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Infantile onset spinocerebellar ataxia in Orphanet.

Professional guidelines

PubMed

Buzkova J, Nikkanen J, Ahola S, Hakonen AH, Sevastianova K, Hovinen T, Yki-Järvinen H, Pietiläinen KH, Lönnqvist T, Velagapudi V, Carroll CJ, Suomalainen A
EMBO Mol Med 2018 Dec;10(12) doi: 10.15252/emmm.201809091. PMID: 30373890Free PMC Article

Recent clinical studies

Etiology

Singh A, Faruq M, Mukerji M, Dwivedi MK, Pruthi S, Kapoor S
J Child Neurol 2014 Jan;29(1):139-44. Epub 2013 Dec 2 doi: 10.1177/0883073813509015. PMID: 24300164
Jacob FD, Ho ES, Martinez-Ojeda M, Darras BT, Khwaja OS
J Child Neurol 2013 Oct;28(10):1292-5. Epub 2012 Aug 21 doi: 10.1177/0883073812454331. PMID: 22914369
Di Donato S, Gellera C, Mariotti C
Neurol Sci 2001 Jun;22(3):219-28. doi: 10.1007/s100720100017. PMID: 11731874
Koskinen T, Valanne L, Ketonen LM, Pihko H
AJNR Am J Neuroradiol 1995 Aug;16(7):1427-33. PMID: 7484627Free PMC Article
Nikali K, Koskinen T, Suomalainen A, Pihko H, Peltonen L
Pediatr Res 1994 Nov;36(5):607-12. doi: 10.1203/00006450-199411000-00012. PMID: 7877879

Diagnosis

Jacob FD, Ho ES, Martinez-Ojeda M, Darras BT, Khwaja OS
J Child Neurol 2013 Oct;28(10):1292-5. Epub 2012 Aug 21 doi: 10.1177/0883073812454331. PMID: 22914369
De Michele G, Filla A
Handb Clin Neurol 2012;103:343-57. doi: 10.1016/B978-0-444-51892-7.00021-8. PMID: 21827899
Di Donato S, Gellera C, Mariotti C
Neurol Sci 2001 Jun;22(3):219-28. doi: 10.1007/s100720100017. PMID: 11731874
Koskinen T, Pihko H, Voutilainen R
Neuropediatrics 1995 Oct;26(5):263-6. doi: 10.1055/s-2007-979769. PMID: 8552218
Koskinen T, Valanne L, Ketonen LM, Pihko H
AJNR Am J Neuroradiol 1995 Aug;16(7):1427-33. PMID: 7484627Free PMC Article

Therapy

Lönnqvist T, Paetau A, Valanne L, Pihko H
Brain 2009 Jun;132(Pt 6):1553-62. Epub 2009 Mar 20 doi: 10.1093/brain/awp045. PMID: 19304794
Nikali K, Suomalainen A, Terwilliger J, Koskinen T, Weissenbach J, Peltonen L
Am J Hum Genet 1995 May;56(5):1088-95. PMID: 7726163Free PMC Article

Prognosis

Nikkanen J, Forsström S, Euro L, Paetau I, Kohnz RA, Wang L, Chilov D, Viinamäki J, Roivainen A, Marjamäki P, Liljenbäck H, Ahola S, Buzkova J, Terzioglu M, Khan NA, Pirnes-Karhu S, Paetau A, Lönnqvist T, Sajantila A, Isohanni P, Tyynismaa H, Nomura DK, Battersby BJ, Velagapudi V, Carroll CJ, Suomalainen A
Cell Metab 2016 Apr 12;23(4):635-48. Epub 2016 Feb 25 doi: 10.1016/j.cmet.2016.01.019. PMID: 26924217
Lönnqvist T, Paetau A, Valanne L, Pihko H
Brain 2009 Jun;132(Pt 6):1553-62. Epub 2009 Mar 20 doi: 10.1093/brain/awp045. PMID: 19304794
Di Donato S, Gellera C, Mariotti C
Neurol Sci 2001 Jun;22(3):219-28. doi: 10.1007/s100720100017. PMID: 11731874
Koskinen T, Pihko H, Voutilainen R
Neuropediatrics 1995 Oct;26(5):263-6. doi: 10.1055/s-2007-979769. PMID: 8552218
Koskinen T, Valanne L, Ketonen LM, Pihko H
AJNR Am J Neuroradiol 1995 Aug;16(7):1427-33. PMID: 7484627Free PMC Article

Clinical prediction guides

Nikkanen J, Forsström S, Euro L, Paetau I, Kohnz RA, Wang L, Chilov D, Viinamäki J, Roivainen A, Marjamäki P, Liljenbäck H, Ahola S, Buzkova J, Terzioglu M, Khan NA, Pirnes-Karhu S, Paetau A, Lönnqvist T, Sajantila A, Isohanni P, Tyynismaa H, Nomura DK, Battersby BJ, Velagapudi V, Carroll CJ, Suomalainen A
Cell Metab 2016 Apr 12;23(4):635-48. Epub 2016 Feb 25 doi: 10.1016/j.cmet.2016.01.019. PMID: 26924217
Park MH, Woo HM, Hong YB, Park JH, Yoon BR, Park JM, Yoo JH, Koo H, Chae JH, Chung KW, Choi BO, Koo SK
Neurogenetics 2014 Aug;15(3):171-82. Epub 2014 May 10 doi: 10.1007/s10048-014-0405-1. PMID: 24816431Free PMC Article
Bouhlal Y, El-Euch-Fayeche G, Amouri R, Hentati F
Acta Myol 2005 Oct;24(2):155-61. PMID: 16550933
Nikali K, Suomalainen A, Saharinen J, Kuokkanen M, Spelbrink JN, Lönnqvist T, Peltonen L
Hum Mol Genet 2005 Oct 15;14(20):2981-90. Epub 2005 Aug 31 doi: 10.1093/hmg/ddi328. PMID: 16135556
Nikali K, Isosomppi J, Lönnqvist T, Mao JI, Suomalainen A, Peltonen L
Genomics 1997 Jan 15;39(2):185-91. doi: 10.1006/geno.1996.4465. PMID: 9027505

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...