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Spinocerebellar ataxia type 36(SCA36)

MedGen UID:
483339
Concept ID:
C3472711
Disease or Syndrome
Synonym: Spinocerebellar Ataxia Type36
SNOMED CT: Spinocerebellar ataxia type 36 (711158005); Costa de Morte ataxia (711158005); Asidan ataxia (711158005); Spinocerebellar ataxia 36 (711158005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): NOP56 (20p13)
 
Monarch Initiative: MONDO:0013594
OMIM®: 614153
Orphanet: ORPHA276198

Definition

Spinocerebellar ataxia-36 (SCA36) is a slowly progressive neurodegenerative disorder characterized by adult-onset gait ataxia, eye movement abnormalities, tongue fasciculations, and variable upper motor neuron signs. Some affected individuals may develop hearing loss (summary by Garcia-Murias et al., 2012). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). [from OMIM]

Additional description

From MedlinePlus Genetics
Spinocerebellar ataxia type 36 (SCA36) is a condition characterized by progressive problems with movement that typically begin in mid-adulthood. People with this condition initially experience problems with coordination and balance (ataxia). Affected individuals often have exaggerated reflexes (hyperreflexia) and problems with speech (dysarthria). They also usually develop muscle twitches (fasciculations) of the tongue and over time, the muscles in the tongue waste away (atrophy). These tongue problems can cause difficulties swallowing liquids. As the condition progresses, individuals with SCA36 develop muscle atrophy in the legs, forearms, and hands. Another common feature of SCA36 is the atrophy of specialized nerve cells that control muscle movement (motor neurons), which can contribute to the tongue and limb muscle atrophy in affected individuals.

Some people with SCA36 have abnormalities of the eye muscles, which can lead to involuntary eye movements (nystagmus), rapid eye movements (saccades), trouble moving the eyes side-to-side (oculomotor apraxia), and droopy eyelids (ptosis). Sensorineural hearing loss, which is hearing loss caused by changes in the inner ear, may also occur in people with SCA36.

Brain imaging of people with SCA36 shows progressive atrophy of various parts of the brain, particularly within the cerebellum, which is the area of the brain involved in coordinating movements. Over time, the loss of cells in the cerebellum causes the movement problems characteristic of SCA36. In older affected individuals, the frontal lobes of the brain may show atrophy resulting in loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies.

Signs and symptoms of SCA36 typically begin in a person's forties or fifties but can appear anytime during adulthood. People with SCA36 have a normal lifespan and are usually mobile for 15 to 20 years after they are diagnosed.  https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-36

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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).
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.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
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.
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Incoordination
MedGen UID:
141714
Concept ID:
C0520966
Finding
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.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
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.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
EMG: neuropathic changes
MedGen UID:
867363
Concept ID:
C4021727
Finding
The presence of characteristic findings of denervation on electromyography (fibrillations, positive sharp waves, and giant motor unit potentials).
Tongue fasciculations
MedGen UID:
65987
Concept ID:
C0239548
Finding
Fasciculations or fibrillation affecting the tongue muscle.
Tongue atrophy
MedGen UID:
66828
Concept ID:
C0241423
Finding
Wasting of the tongue.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
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.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.
Impaired smooth pursuit
MedGen UID:
325176
Concept ID:
C1837458
Finding
An impairment of the ability to track objects with the ocular smooth pursuit system, a class of rather slow eye movements that minimizes retinal target motion.
Vertical supranuclear gaze palsy
MedGen UID:
334385
Concept ID:
C1843369
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia type 36
Follow this link to review classifications for Spinocerebellar ataxia type 36 in Orphanet.

Professional guidelines

PubMed

Maarouf H, Taboada M, Rodriguez H, Arias M, Sesar Á, Sobrido MJ
BMC Med Inform Decis Mak 2017 Dec 6;17(1):159. doi: 10.1186/s12911-017-0568-4. PMID: 29207981Free PMC Article

Recent clinical studies

Etiology

Wang Q, Zhang C, Liu S, Liu T, Ni R, Liu X, Zhong P, Wu Q, Xu T, Ke H, Tian W, Cao L
Clin Neurol Neurosurg 2022 Dec;223:107503. Epub 2022 Oct 30 doi: 10.1016/j.clineuro.2022.107503. PMID: 36368168
Aguiar P, Pardo J, Arias M, Quintáns B, Fernández-Prieto M, Martínez-Regueiro R, Pumar JM, Silva-Rodríguez J, Ruibal Á, Sobrido MJ, Cortés J
Mov Disord 2017 Feb;32(2):264-273. Epub 2016 Nov 10 doi: 10.1002/mds.26854. PMID: 27862279
Arias M, García-Murias M, Sobrido MJ
Neurologia 2017 Jul-Aug;32(6):386-393. Epub 2015 Jan 13 doi: 10.1016/j.nrl.2014.11.005. PMID: 25593102
Zeng S, Zeng J, He M, Zeng X, Zhou Y, Liu Z, Xia K, Pan Q, Jiang H, Shen L, Yan X, Tang B, Wang J
Clin Genet 2016 Aug;90(2):141-8. Epub 2016 Jan 20 doi: 10.1111/cge.12706. PMID: 26661328
Ikeda Y, Ohta Y, Kurata T, Shiro Y, Takao Y, Abe K
J Neurol Sci 2013 Jan 15;324(1-2):109-12. Epub 2012 Nov 7 doi: 10.1016/j.jns.2012.10.013. PMID: 23140984

Diagnosis

Chen R, Zhou C, Peng Y, Huang P, Yu Y, Zhu M, Zhou M, Hong D, Tan D
Neurodegener Dis 2024;24(2):71-79. Epub 2024 Jun 26 doi: 10.1159/000540006. PMID: 38934198
Wang Q, Zhang C, Liu S, Liu T, Ni R, Liu X, Zhong P, Wu Q, Xu T, Ke H, Tian W, Cao L
Clin Neurol Neurosurg 2022 Dec;223:107503. Epub 2022 Oct 30 doi: 10.1016/j.clineuro.2022.107503. PMID: 36368168
Aguiar P, Pardo J, Arias M, Quintáns B, Fernández-Prieto M, Martínez-Regueiro R, Pumar JM, Silva-Rodríguez J, Ruibal Á, Sobrido MJ, Cortés J
Mov Disord 2017 Feb;32(2):264-273. Epub 2016 Nov 10 doi: 10.1002/mds.26854. PMID: 27862279
Arias M, García-Murias M, Sobrido MJ
Neurologia 2017 Jul-Aug;32(6):386-393. Epub 2015 Jan 13 doi: 10.1016/j.nrl.2014.11.005. PMID: 25593102
Ikeda Y, Ohta Y, Kurata T, Shiro Y, Takao Y, Abe K
J Neurol Sci 2013 Jan 15;324(1-2):109-12. Epub 2012 Nov 7 doi: 10.1016/j.jns.2012.10.013. PMID: 23140984

Prognosis

Aguiar P, Pardo J, Arias M, Quintáns B, Fernández-Prieto M, Martínez-Regueiro R, Pumar JM, Silva-Rodríguez J, Ruibal Á, Sobrido MJ, Cortés J
Mov Disord 2017 Feb;32(2):264-273. Epub 2016 Nov 10 doi: 10.1002/mds.26854. PMID: 27862279

Clinical prediction guides

Maarouf H, Taboada M, Rodriguez H, Arias M, Sesar Á, Sobrido MJ
BMC Med Inform Decis Mak 2017 Dec 6;17(1):159. doi: 10.1186/s12911-017-0568-4. PMID: 29207981Free PMC Article
Ikeda Y, Ohta Y, Kobayashi H, Okamoto M, Takamatsu K, Ota T, Manabe Y, Okamoto K, Koizumi A, Abe K
Neurology 2012 Jul 24;79(4):333-41. Epub 2012 Jun 27 doi: 10.1212/WNL.0b013e318260436f. PMID: 22744658

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