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Spastic ataxia Charlevoix-Saguenay type(SACS)

MedGen UID:
338620
Concept ID:
C1849140
Disease or Syndrome
Synonyms: Autosomal recessive spastic ataxia of Charlevoix-Saguenay; SACS; SPASTIC ATAXIA 6, AUTOSOMAL RECESSIVE; Spastic ataxia of Charlevoix-Saguenay
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 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).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: ARSACS - autosomal recessive spastic ataxia of Charlevoix-Saguenay (702445005); Autosomal recessive spastic ataxia of Charlevoix-Saguenay (702445005); Spastic ataxia of Charlevoix-Saguenay (702445005)
 
Gene (location): SACS (13q12.12)
OMIM®: 270550
Orphanet: ORPHA98

Disease characteristics

Excerpted from the GeneReview: ARSACS
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is clinically characterized by a progressive cerebellar ataxia, peripheral neuropathy, and spasticity. Disease onset of classic ARSACS is often in early childhood, leading to delayed walking because of gait unsteadiness in very young toddlers, while an increasing number of individuals with disease onset in teenage or early-adult years are now being described. Typically the ataxia is followed by lower-limb spasticity and later by peripheral neuropathy – although pronounced peripheral neuropathy has been observed as a first sign of ARSACS. Oculomotor disturbances, dysarthria, and upper-limb ataxia develop with slower progression than the other findings. Brain imaging demonstrates atrophy of the superior vermis and the cerebellar hemisphere with additional findings on MRI, such as linear hypointensities in the pons and hyperintense rims around the thalami. Many affected individuals (though not all) have yellow streaks of hypermyelinated fibers radiating from the edges of the optic disc noted on ophthalmologic exam, and thickened retinal fibers can be demonstrated by optical coherence tomography. Mild intellectual disability, hearing loss, and urinary urgency and incontinence have been reported in some individuals. [from GeneReviews]
Authors:
Sascha Vermeer  |  Bart P van de Warrenburg  |  Erik-Jan Kamsteeg, et. al.   view full author information

Additional descriptions

From OMIM
Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a complex neurodegenerative disorder usually characterized by early childhood onset of cerebellar ataxia, pyramidal tract signs, and peripheral neuropathy. Most patients become wheelchair-bound; cognitive function is usually not affected. Some patients may have atypical features, such as later onset or initial presentation of peripheral neuropathy (summary by Baets et al., 2010).  http://www.omim.org/entry/270550
From GHR
Autosomal recessive spastic ataxia of Charlevoix-Saguenay, more commonly known as ARSACS, is a condition affecting muscle movement. People with ARSACS typically have abnormal tensing of the muscles (spasticity), problems with balance and coordination (cerebellar ataxia), and reduced sensation and weakness in the arms and legs (peripheral neuropathy).Additional muscle problems that can occur in ARSACS include muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and difficulty swallowing (dysphagia) and speaking (dysarthria). Other features of ARSACS involve high-arched feet (pes cavus), a spine that curves to the side (scoliosis), yellow streaks of fatty tissue in the light-sensitive tissue at the back of the eye (hypermyelination of the retina), urinary tract problems, intellectual disability, hearing loss, and recurrent seizures (epilepsy).An unsteady walking style (gait) is the first symptom of ARSACS. Walking problems usually begin between the ages of 12 months and 18 months, as toddlers are learning to walk. These movement problems worsen over time, with increased spasticity and ataxia of the arms and legs. In some cases spasticity goes away, but this apparent improvement is thought to be due to the wasting away (atrophy) of nerves in the arms and legs. Most affected individuals require wheelchair assistance by the time they are in their thirties or forties.While this condition was named after the area in which it was first seen, the Charlevoix-Saguenay region of Quebec, Canada, ARSACS has been identified in individuals worldwide.  https://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay

Clinical features

From HPO
Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
An acute and compelling urge to urinate.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from CRANIAL NERVE DISEASES; NEUROMUSCULAR DISEASES; CEREBELLAR DISEASES; BASAL GANGLIA DISEASES; BRAIN STEM diseases; or diseases of the corticobulbar tracts (see PYRAMIDAL TRACTS). The cortical language centers are intact in this condition. (From Adams et al., Principles of Neurology, 6th ed, p489)
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a "free interval") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
A reflex characterized by upward movement of the great toe and an outward movement of the rest of the toes, when the sole of the foot is stroked. It is a normal reflex up to the age of two. Its presence beyond that age indicates neurological damage.
Falls
MedGen UID:
39084
Concept ID:
C0085639
Finding
A sudden movement downward, usually resulting in injury.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Autonomic nervous system overreaction to stimuli, most commonly after spinal cord injury at a T-5 level and above.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Scanning speech
MedGen UID:
82928
Concept ID:
C0278184
Sign or Symptom
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Cerebellar vermis atrophy
MedGen UID:
149271
Concept ID:
C0742028
Finding
Wasting (atrophy) of the vermis of cerebellum.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Progressive gait ataxia
MedGen UID:
375309
Concept ID:
C1843885
Finding
A type of gait ataxia displaying progression of clinical severity.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Impaired vibration sensation in the lower limbs
MedGen UID:
338617
Concept ID:
C1849134
Finding
A decrease in the ability to perceive vibration in the legs.
Progressive truncal ataxia
MedGen UID:
341389
Concept ID:
C1849143
Finding
Loss of Purkinje cells in the cerebellar vermis
MedGen UID:
336510
Concept ID:
C1849146
Finding
Decreased sensory nerve conduction velocity
MedGen UID:
336512
Concept ID:
C1849148
Finding
Reduced speed of conduction of the action potential along a sensory nerve.
Hypermyelinated retinal nerve fibers
MedGen UID:
336515
Concept ID:
C1849151
Finding
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Decreased number of large peripheral myelinated nerve fibers
MedGen UID:
395303
Concept ID:
C1859606
Finding
A reduced number of large myelinated nerve fibers.
Spastic ataxia
MedGen UID:
462969
Concept ID:
C3151619
Disease or Syndrome
This progressive neurodegenerative disorder is characterized by early childhood onset of spastic ataxia with mental retardation, cerebellar signs, and variable optic atrophy (Hogan and Bauman, 1977).
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Swan neck-like deformities of the fingers
MedGen UID:
336516
Concept ID:
C1849152
Finding
A swan neck deformity describes a finger with a hyperextended PIP joint and a flexed DIP joint. The most common cause for a swan neck-like deformity is a disruption of the end of the extensor tendon. Conditions that loosen the PIP joint and allow it to hyperextend, for example conditions that weaken the volar plate, can produce a swan neck deformity of the finger. One example is rheumatoid arthritis. Another cause are conditions that tighten up the small (intrinsic) muscles of the hand and fingers, for example hand trauma or nerve disorders, such as cerebral palsy, Parkinson's disease, or stroke.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a "free interval") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Swan neck-like deformities of the fingers
MedGen UID:
336516
Concept ID:
C1849152
Finding
A swan neck deformity describes a finger with a hyperextended PIP joint and a flexed DIP joint. The most common cause for a swan neck-like deformity is a disruption of the end of the extensor tendon. Conditions that loosen the PIP joint and allow it to hyperextend, for example conditions that weaken the volar plate, can produce a swan neck deformity of the finger. One example is rheumatoid arthritis. Another cause are conditions that tighten up the small (intrinsic) muscles of the hand and fingers, for example hand trauma or nerve disorders, such as cerebral palsy, Parkinson's disease, or stroke.
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)
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.
Hypermyelinated retinal nerve fibers
MedGen UID:
336515
Concept ID:
C1849151
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpastic ataxia Charlevoix-Saguenay type
Follow this link to review classifications for Spastic ataxia Charlevoix-Saguenay type in Orphanet.

Professional guidelines

PubMed

van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O
Eur J Neurol 2014 Apr;21(4):552-62. Epub 2014 Jan 13 doi: 10.1111/ene.12341. PMID: 24418350

Recent clinical studies

Etiology

Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Neurology 2019 Oct 15;93(16):e1543-e1549. Epub 2019 Sep 18 doi: 10.1212/WNL.0000000000008313. PMID: 31534027Free PMC Article
Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Orphanet J Rare Dis 2018 Sep 19;13(1):165. doi: 10.1186/s13023-018-0898-z. PMID: 30231904Free PMC Article
Gagnon C, Lessard I, Lavoie C, Côté I, St-Gelais R, Mathieu J, Brais B
Neurology 2018 Oct 2;91(14):e1307-e1311. Epub 2018 Aug 29 doi: 10.1212/WNL.0000000000006290. PMID: 30158165Free PMC Article
Gagnon C, Lessard I, Brais B, Côté I, Lavoie C, Synofzik M, Mathieu J
Arch Phys Med Rehabil 2018 Sep;99(9):1747-1754. Epub 2018 Feb 17 doi: 10.1016/j.apmr.2018.01.026. PMID: 29462597
Tardif J, Pratte A, Laberge AM
Prenat Diagn 2018 Jan;38(1):67-74. Epub 2017 May 12 doi: 10.1002/pd.5055. PMID: 28419508

Diagnosis

Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Neurology 2019 Oct 15;93(16):e1543-e1549. Epub 2019 Sep 18 doi: 10.1212/WNL.0000000000008313. PMID: 31534027Free PMC Article
Kuchay RAH, Mir YR, Zeng X, Hassan A, Musarrat J, Parwez I, Kernstock C, Traschütz A, Synofzik M
Cerebellum 2019 Aug;18(4):807-812. doi: 10.1007/s12311-019-01028-2. PMID: 30963395
Ricca I, Morani F, Bacci GM, Nesti C, Caputo R, Tessa A, Santorelli FM
Neurogenetics 2019 Mar;20(1):45-49. Epub 2019 Jan 24 doi: 10.1007/s10048-019-00564-7. PMID: 30680480
Rezende Filho FM, Pedroso JL, Barsottini OGP
JAMA Neurol 2018 Dec 1;75(12):1566-1567. doi: 10.1001/jamaneurol.2018.3108. PMID: 30326009
Biswas A, Varman M, Yoganathan S, Subhash PK, Mani S
Neurology 2018 Apr 3;90(14):e1271-e1272. doi: 10.1212/WNL.0000000000005252. PMID: 29610238

Therapy

Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Orphanet J Rare Dis 2018 Sep 19;13(1):165. doi: 10.1186/s13023-018-0898-z. PMID: 30231904Free PMC Article
Pedroso JL, Braga-Neto P, Abrahão A, Rivero RL, Abdalla C, Abdala N, Barsottini OG
Arq Neuropsiquiatr 2011;69(2B):288-91. doi: 10.1590/s0004-282x2011000300004. PMID: 21625752
Bouhlal Y, Amouri R, El Euch-Fayeche G, Hentati F
Parkinsonism Relat Disord 2011 Jul;17(6):418-22. Epub 2011 Mar 30 doi: 10.1016/j.parkreldis.2011.03.005. PMID: 21450511

Prognosis

Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Neurology 2019 Oct 15;93(16):e1543-e1549. Epub 2019 Sep 18 doi: 10.1212/WNL.0000000000008313. PMID: 31534027Free PMC Article
Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Orphanet J Rare Dis 2018 Sep 19;13(1):165. doi: 10.1186/s13023-018-0898-z. PMID: 30231904Free PMC Article
Gagnon C, Lessard I, Lavoie C, Côté I, St-Gelais R, Mathieu J, Brais B
Neurology 2018 Oct 2;91(14):e1307-e1311. Epub 2018 Aug 29 doi: 10.1212/WNL.0000000000006290. PMID: 30158165Free PMC Article
Ménade M, Kozlov G, Trempe JF, Pande H, Shenker S, Wickremasinghe S, Li X, Hojjat H, Dicaire MJ, Brais B, McPherson PS, Wong MJH, Young JC, Gehring K
J Biol Chem 2018 Aug 17;293(33):12832-12842. Epub 2018 Jun 26 doi: 10.1074/jbc.RA118.003939. PMID: 29945973Free PMC Article
Zeng H, Tang JG, Yang YF, Tan ZP, Tan JQ
Cytogenet Genome Res 2017;152(1):16-21. Epub 2017 Jun 29 doi: 10.1159/000477428. PMID: 28658676

Clinical prediction guides

Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Neurology 2019 Oct 15;93(16):e1543-e1549. Epub 2019 Sep 18 doi: 10.1212/WNL.0000000000008313. PMID: 31534027Free PMC Article
Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Orphanet J Rare Dis 2018 Sep 19;13(1):165. doi: 10.1186/s13023-018-0898-z. PMID: 30231904Free PMC Article
Gagnon C, Lessard I, Lavoie C, Côté I, St-Gelais R, Mathieu J, Brais B
Neurology 2018 Oct 2;91(14):e1307-e1311. Epub 2018 Aug 29 doi: 10.1212/WNL.0000000000006290. PMID: 30158165Free PMC Article
Vogel AP, Rommel N, Oettinger A, Stoll LH, Kraus EM, Gagnon C, Horger M, Krumm P, Timmann D, Storey E, Schöls L, Synofzik M
J Neurol 2018 Sep;265(9):2060-2070. Epub 2018 Jul 2 doi: 10.1007/s00415-018-8950-4. PMID: 29968200
Gagnon C, Lessard I, Brais B, Côté I, Lavoie C, Synofzik M, Mathieu J
Arch Phys Med Rehabil 2018 Sep;99(9):1747-1754. Epub 2018 Feb 17 doi: 10.1016/j.apmr.2018.01.026. PMID: 29462597

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