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Spastic paraplegia 4, autosomal dominant(SPG4)

MedGen UID:
401097
Concept ID:
C1866855
Disease or Syndrome
Synonyms: Autosomal Dominant Hereditary Spastic Paraplegia; Familial spastic paraplegia autosomal dominant 2; Hereditary Spastic Paraplegia; Spastic Paraplegia 4; Spastic paraplegia 4; spastic paraplegia type 4; SPG4
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Genetic anticipation
MedGen UID:
109454
Concept ID:
C0600498
Organism Attribute
The apparent tendency of certain diseases to appear at earlier AGE OF ONSET and with increasing severity in successive generations. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
 
Gene: SPAST
Cytogenetic location: 2p22.3
OMIM®: 182601
Orphanet: ORPHA100985

Disease characteristics

Excerpted from the GeneReview: Spastic Paraplegia 4
Spastic paraplegia 4 (SPG4; also known as SPAST-associated HSP) is characterized by insidiously progressive bilateral lower-limb gait spasticity. More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles. About one third have sphincter disturbances. Onset is insidious, mostly in young adulthood, although symptoms may start as early as age one year and as late as age 76 years. Intrafamilial variation is considerable.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Alexandra Dürr  |  Chantal Tallaksen  |  Christel Depienne   view full author information

Additional descriptions

From OMIM
The hereditary spastic paraplegias (SPG, HSP) are a group of clinically and genetically diverse inherited disorders characterized predominantly by progressive lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated') or with other neurologic abnormalities ('complicated'). Pure SPG4 is the most common form of autosomal dominant hereditary SPG, comprising up to 45% of cases (Svenson et al., 2001; Crippa et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).  http://www.omim.org/entry/182601
From GHR
Spastic paraplegia type 4 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and the nervous system. Spastic paraplegia type 4 is a pure hereditary spastic paraplegia. Like all hereditary spastic paraplegias, spastic paraplegia type 4 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), ankle spasms, high-arched feet (pes cavus), and reduced bladder control. Spastic paraplegia type 4 generally affects nerve and muscle function in the lower half of the body only.  http://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4

Clinical features

Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
A sudden compelling urge to urinate.
Urinary bladder sphincter dysfunction
MedGen UID:
334804
Concept ID:
C1843663
Finding
Urinary incontinence
MedGen UID:
776587
Concept ID:
C2712331
Finding
Nystagmus
MedGen UID:
409575
Concept ID:
C1963184
Finding
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Spastic gait
MedGen UID:
115907
Concept ID:
C0231687
Finding
Depression
MedGen UID:
137999
Concept ID:
C0344315
Finding
Apathy
MedGen UID:
612589
Concept ID:
C0436596
Finding
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Degeneration of the lateral corticospinal tracts
MedGen UID:
375921
Concept ID:
C1846566
Finding
Spastic paraplegia
MedGen UID:
335468
Concept ID:
C1846589
Finding
Memory impairment
MedGen UID:
368424
Concept ID:
C1963167
Finding
Agitation
MedGen UID:
504568
Concept ID:
CN000670
Finding
Aggressive behavior
MedGen UID:
504570
Concept ID:
CN000675
Finding
Aggressive behavior can denote verbal aggression, physical aggression against objects, physical aggression against people, and may also include aggression towards oneself.
Dementia
MedGen UID:
504574
Concept ID:
CN000683
Finding
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Disinhibition
MedGen UID:
504576
Concept ID:
CN000690
Finding
A lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment.
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.
Paraplegia
MedGen UID:
506382
Concept ID:
CN009381
Finding
Severe or complete weakness of both lower extremities with sparing of the upper extremities.
Low back pain
MedGen UID:
505536
Concept ID:
CN003084
Finding
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the lower back.
Spastic gait
MedGen UID:
115907
Concept ID:
C0231687
Finding
Spastic paraplegia
MedGen UID:
335468
Concept ID:
C1846589
Finding
Lower limb muscle weakness
MedGen UID:
446811
Concept ID:
CN006423
Finding
Weakness of the muscles of the legs.
Lower limb muscle weakness
MedGen UID:
446811
Concept ID:
CN006423
Finding
Weakness of the muscles of the legs.

Recent clinical studies

Prognosis

Boone PM, Yuan B, Campbell IM, Scull JC, Withers MA, Baggett BC, Beck CR, Shaw CJ, Stankiewicz P, Moretti P, Goodwin WE, Hein N, Fink JK, Seong MW, Seo SH, Park SS, Karbassi ID, Batish SD, Ordóñez-Ugalde A, Quintáns B, Sobrido MJ, Stemmler S, Lupski JR
Am J Hum Genet 2014 Aug 7;95(2):143-61. Epub 2014 Jul 24 doi: 10.1016/j.ajhg.2014.06.014. [Epub ahead of print] PMID: 25065914Free PMC Article

Clinical prediction guides

Boone PM, Yuan B, Campbell IM, Scull JC, Withers MA, Baggett BC, Beck CR, Shaw CJ, Stankiewicz P, Moretti P, Goodwin WE, Hein N, Fink JK, Seong MW, Seo SH, Park SS, Karbassi ID, Batish SD, Ordóñez-Ugalde A, Quintáns B, Sobrido MJ, Stemmler S, Lupski JR
Am J Hum Genet 2014 Aug 7;95(2):143-61. Epub 2014 Jul 24 doi: 10.1016/j.ajhg.2014.06.014. [Epub ahead of print] PMID: 25065914Free PMC Article
Miura S, Shibata H, Kida H, Noda K, Toyama T, Iwasaki N, Iwaki A, Ayabe M, Aizawa H, Taniwaki T, Fukumaki Y
Neurogenetics 2011 Feb;12(1):25-31. Epub 2010 Sep 22 doi: 10.1007/s10048-010-0260-7. [Epub ahead of print] PMID: 20857310

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