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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; Charlevoix-Saguenay spastic ataxia; 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
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
 
Gene: SACS
Cytogenetic location: 13q12.12
OMIM: 270550

Disease characteristics

Excerpted from the GeneReview: ARSACS
ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is characterized in individuals born in Quebec Province by early-onset (age 12-18 months) difficulty in walking and gait unsteadiness. In individuals with ARSACS born outside the Province of Quebec, onset is often delayed until later childhood and even adulthood. Ataxia, dysarthria, spasticity, extensor plantar reflexes, distal muscle wasting, a distal sensorimotor neuropathy predominant in the legs, and horizontal gaze-evoked nystagmus constitute the most frequent progressive neurologic signs. Increased demarcation of the retinal nerve fibers located near the vessels close to the optic disc (formerly designated as yellow streaks of hypermyelinated fibers) is very common in individuals with ARSACS who originate from Quebec but may be absent in non-Quebec born individuals. Individuals with ARSACS born in the Province of Quebec become wheelchair bound at the average age of 41 years; cognitive skills are preserved in the long term as individuals remain able to perform daily living tasks late into adulthood. Death commonly occurs in the sixth decade.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Sascha Vermeer  |  Bart P van de Warrenburg  |  Erik-Jan Kamsteeg   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), difficulty coordinating movements (ataxia), muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and speech difficulties (dysarthria). Other problems may include deformities of the fingers and feet, reduced sensation and weakness in the arms and legs (peripheral neuropathy), yellow streaks of fatty tissue in the light-sensitive tissue at the back of the eye (hypermyelination of the retina), and less commonly, leaks in one of the valves that control blood flow through the heart (mitral valve prolapse). An unsteady gait is the first symptom of ARSACS. It usually appears between the age of 12 months and 18 months, as toddlers are learning to walk. The signs and symptoms worsen over the years, with increased spasticity and ataxia of the arms and legs. In some cases spasticity disappears, but this apparent improvement is thought to be due to degeneration of nerves in the arms and legs. Most affected individuals require a wheelchair by the time they are in their thirties or forties. This condition was first seen in people of the Charlevoix-Saguenay region of Quebec, Canada. The majority of people with ARSACS live in Quebec or have recent ancestors from Quebec. People with ARSACS have also been identified in Japan, Turkey, Tunisia, Spain, Italy, and Belgium. The signs and symptoms of ARSACS seen in other countries differ from those in Quebec. In people with ARSACS outside of Quebec, hypermyelination of the retina is seen less often, intelligence may be below normal, and symptoms tend to appear at a later age.  http://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay

Clinical features

Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
A sudden compelling urge to urinate.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
An abnormal reflex consisting of dorsiflexion of the great toe and abduction of the other toes in response to cutaneous stimulation of the plantar surface of the foot.
Falls
MedGen UID:
39084
Concept ID:
C0085639
Finding
A fall can change your life. If you're elderly, it can lead to disability and a loss of independence. If your bones are fragile from osteoporosis, you could break a bone, often a hip. But aging alone doesn't make people fall. Diabetes and heart disease affect balance. So do problems with circulation, thyroid or nervous systems. Some medicines make people dizzy. Eye problems or alcohol can be factors. Any of these things can make a fall more likely. Babies and young children are also at risk of falling - off of furniture and down stairs, for example. Falls and accidents seldom just happen. Taking care of your health by exercising and getting regular eye exams and physicals may help reduce your chance of falling. Getting rid of tripping hazards in your home and wearing nonskid shoes may also help. To reduce the chances of breaking a bone if you do fall, make sure that you get enough calcium and vitamin D. . NIH: National Institute on Aging.
Decreased nerve conduction velocity
MedGen UID:
500893
Concept ID:
CN000716
Finding
A reduction in the speed at which electrical signals propagate along the axon of a `neuron` (FMA:54527).
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Impaired vibration sensation in the lower limbs
MedGen UID:
505135
Concept ID:
CN001963
Finding
A decrease in the ability to perceive vibration in the legs.
Decreased number of large peripheral myelinated nerve fibers
MedGen UID:
505529
Concept ID:
CN003056
Finding
A reduced number of large myelinated nerve fibers.
Cerebellar vermis atrophy
MedGen UID:
505991
Concept ID:
CN005971
Finding
Wasting (atrophy) of the `vermis of cerebellum` (FMA:76928).
Pes cavus
MedGen UID:
425071
Concept ID:
CN001601
Finding
The presence of an unusually high `plantar arch` (FMA:43942). 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:
504946
Concept ID:
CN001605
Finding
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Distal amyotrophy
MedGen UID:
505575
Concept ID:
CN003339
Finding
Muscular atrophy affecting muscles in the distal portions of the extremities.

Recent clinical studies

Etiology

Chen Z, Wang JL, Tang BS, Sun ZF, Shi YT, Shen L, Lei LF, Wei XM, Xiao JJ, Hu ZM, Pan Q, Xia K, Zhang QY, Dai MZ, Liu Y, Ashizawa T, Jiang H
Neurobiol Aging 2013 Oct;34(10):2442.e11-7. Epub 2013 May 30 doi: 10.1016/j.neurobiolaging.2013.04.029. [Epub ahead of print] PMID: 23726790
Thiffault I, Dicaire MJ, Tetreault M, Huang KN, Demers-Lamarche J, Bernard G, Duquette A, Larivière R, Gehring K, Montpetit A, McPherson PS, Richter A, Montermini L, Mercier J, Mitchell GA, Dupré N, Prévost C, Bouchard JP, Mathieu J, Brais B
Can J Neurol Sci 2013 Jan;40(1):61-6. PMID: 23250129

Diagnosis

Pyle A, Griffin H, Duff J, Bennett S, Zwolinski S, Smertenko T, Yu-Wai Man P, Santibanez-Koref M, Horvath R, Chinnery PF
J Neurogenet 2013 Dec;27(4):176-82. Epub 2013 Nov 4 doi: 10.3109/01677063.2013.831094. [Epub ahead of print] PMID: 24180463Free PMC Article
Garcia-Martin E, Pablo LE, Gazulla J, Vela A, Larrosa JM, Polo V, Marques ML, Alfaro J
Invest Ophthalmol Vis Sci 2013 Oct 29;54(10):7137-42. doi: 10.1167/iovs.13-12726. PMID: 24114536
Duquette A, Brais B, Bouchard JP, Mathieu J
Mov Disord 2013 Dec;28(14):2011-4. Epub 2013 Aug 2 doi: 10.1002/mds.25604. [Epub ahead of print] PMID: 23913799
Chen Z, Wang JL, Tang BS, Sun ZF, Shi YT, Shen L, Lei LF, Wei XM, Xiao JJ, Hu ZM, Pan Q, Xia K, Zhang QY, Dai MZ, Liu Y, Ashizawa T, Jiang H
Neurobiol Aging 2013 Oct;34(10):2442.e11-7. Epub 2013 May 30 doi: 10.1016/j.neurobiolaging.2013.04.029. [Epub ahead of print] PMID: 23726790
McElroy JP, Krupp LB, Johnson BA, McCauley JL, Qi Z, Caillier SJ, Gourraud PA, Yu J, Nathanson L, Belman AL, Hauser SL, Waubant E, Hedges DJ, Oksenberg JR
Mult Scler 2013 Jul;19(8):1014-21. Epub 2012 Dec 13 doi: 10.1177/1352458512469696. [Epub ahead of print] PMID: 23239789

Therapy

Pedroso JL, Braga-Neto P, Abrahão A, Rivero RL, Abdalla C, Abdala N, Barsottini OG
Arq Neuropsiquiatr 2011;69(2B):288-91. 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. [Epub ahead of print] PMID: 21450511

Prognosis

Mignarri A, Tessa A, Carluccio MA, Rufa A, Storti E, Bonelli G, Marcotulli C, Santorelli FM, Leonardi L, Casali C, Federico A, Dotti MT
Neurol Sci 2014 Jan;35(1):95-7. Epub 2013 Dec 7 doi: 10.1007/s10072-013-1592-5. [Epub ahead of print] PMID: 24318559
McElroy JP, Krupp LB, Johnson BA, McCauley JL, Qi Z, Caillier SJ, Gourraud PA, Yu J, Nathanson L, Belman AL, Hauser SL, Waubant E, Hedges DJ, Oksenberg JR
Mult Scler 2013 Jul;19(8):1014-21. Epub 2012 Dec 13 doi: 10.1177/1352458512469696. [Epub ahead of print] PMID: 23239789

Clinical prediction guides

Liew WK, Ben-Omran T, Darras BT, Prabhu SP, De Vivo DC, Vatta M, Yang Y, Eng CM, Chung WK
JAMA Neurol 2013 Jun;70(6):788-91. doi: 10.1001/jamaneurol.2013.247. PMID: 23699708
Synofzik M, Soehn AS, Gburek-Augustat J, Schicks J, Karle KN, Schüle R, Haack TB, Schöning M, Biskup S, Rudnik-Schöneborn S, Senderek J, Hoffmann KT, MacLeod P, Schwarz J, Bender B, Krüger S, Kreuz F, Bauer P, Schöls L
Orphanet J Rare Dis 2013 Mar 15;8:41. doi: 10.1186/1750-1172-8-41. [Epub ahead of print] PMID: 23497566Free PMC Article
Romano A, Tessa A, Barca A, Fattori F, de Leva MF, Terracciano A, Storelli C, Santorelli FM, Verri T
Hum Mutat 2013 Mar;34(3):525-37. doi: 10.1002/humu.22269. PMID: 23280630Free PMC Article
Verhoeven WM, Egger JI, Ahmed AI, Kremer BP, Vermeer S, van de Warrenburg BP
Psychopathology 2012;45(3):193-9. Epub 2012 Mar 22 doi: 10.1159/000331319. [Epub ahead of print] PMID: 22441213
Girard M, Larivière R, Parfitt DA, Deane EC, Gaudet R, Nossova N, Blondeau F, Prenosil G, Vermeulen EG, Duchen MR, Richter A, Shoubridge EA, Gehring K, McKinney RA, Brais B, Chapple JP, McPherson PS
Proc Natl Acad Sci U S A 2012 Jan 31;109(5):1661-6. Epub 2012 Jan 17 doi: 10.1073/pnas.1113166109. [Epub ahead of print] PMID: 22307627Free PMC Article

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