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Mitochondrial DNA depletion syndrome 7 (hepatocerebral type)(MTDPS7)

MedGen UID:
338613
Concept ID:
C1849096
Disease or Syndrome
Synonyms: C10orf2-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form; MTDPS7; Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis; OPHTHALMOPLEGIA, HYPOTONIA, ATAXIA, HYPOACUSIS, AND ATHETOSIS; SCA8 (formerly); SPINOCEREBELLAR ATAXIA 8; Spinocerebellar ataxia 8 (formerly); Spinocerebellar ataxia infantile with sensory neuropathy; Spinocerebellar ataxia, infantile-onset
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:curators]
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Infantile onset spinocerebellar ataxia (724227000); Ohaha syndrome (724227000); Ophthalmoplegia, hypotonia, ataxia, hypoacusis, athetosis syndrome (724227000)
 
Gene (location): TWNK (10q24.31)
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 GHR
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://ghr.nlm.nih.gov/condition/infantile-onset-spinocerebellar-ataxia

Clinical features

Athetosis
MedGen UID:
2115
Concept ID:
C0004158
Sign or Symptom
A dyskinesia characterized by an inability to maintain the fingers, toes, tongue, or other body parts in a stable position, resulting in continuous slow, sinusoidal, and flowing involuntary movements. This condition is frequently accompanied by CHOREA, where it is referred to as choreoathetosis. Athetosis may occur as a manifestation of BASAL GANGLIA DISEASES or DRUG TOXICITY. (From Adams et al., Principles of Neurology, 6th ed, p76)
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- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Hearing impairment
MedGen UID:
5453
Concept ID:
C0018772
Finding
A decreased magnitude of the sensory perception of sound.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)
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
A disorder characterized by loss of optic nerve fibers. It may be inherited or acquired. Acquired causes include ischemia, optic nerve neuropathy, glaucoma, trauma, radiation, brain tumors, and multiple sclerosis. It leads to vision disturbances.
Psychosis
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes of personality and thought patterns often accompanied by hallucinations and delusional beliefs.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
A life-threatening situation in which the brain is in a continuous state of seizure.
Epilepsia partialis continua
MedGen UID:
39303
Concept ID:
C0085543
Disease or Syndrome
A form of partial status epilepticus with simple motor manifestations that are maintained for over one hour, with clonic activity restricted to one body part and recurring at fairly regular intervals.
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.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A reduction in the strength of one or more 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.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
A finding indicating the complete absence of neurological reflexes.
Brain atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. [HPO:sdoelken]
Epileptic encephalopathy
MedGen UID:
452596
Concept ID:
C0543888
Disease or Syndrome
Hypergonadotropic hypogonadism
MedGen UID:
184926
Concept ID:
C0948896
Disease or Syndrome
Ovarian or testicular dysfunction associated with high levels of gonadotropins.
Poor eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
Difficulty in looking at another person in the eye.
Sensory axonal neuropathy
MedGen UID:
334116
Concept ID:
C1842587
Finding
An axonal neuropathy of peripheral sensory nerves.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Elevated hepatic transaminases
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Loss of ability to walk
MedGen UID:
338614
Concept ID:
C1849097
Finding
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Encephalopathy
MedGen UID:
368408
Concept ID:
C1963101
Finding
Excessive daytime somnolence
MedGen UID:
417941
Concept ID:
C2830004
Mental or Behavioral Dysfunction
A sleep disorder characterized by excessive sleepiness and drowsiness.
Cerebellar atrophy
MedGen UID:
892891
Concept ID:
C4020873
Disease or Syndrome
Atrophy (wasting) of the cerebellum.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) in Orphanet.

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