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Hereditary spastic paraplegia 8(SPG8)

MedGen UID:
400359
Concept ID:
C1863704
Disease or Syndrome
Synonyms: Spastic paraplegia 8; SPASTIC PARAPLEGIA 8, AUTOSOMAL DOMINANT; SPG8
SNOMED CT: Autosomal dominant spastic paraplegia type 8 (785305006)
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): WASHC5 (8q24.13)
 
Monarch Initiative: MONDO:0011339
OMIM®: 603563
Orphanet: ORPHA100989

Disease characteristics

Excerpted from the GeneReview: Spastic Paraplegia 8
Hereditary spastic paraplegia 8 (SPG8) is a slowly progressive pure spastic paraplegia of the lower limbs (i.e., pyramidal signs including hyperreflexia, spasticity, and occasionally clonus without other neurologic findings). Some affected individuals have urinary urgency that usually becomes apparent at the same time as the spasticity. Onset is between ages ten and 59 years. Affected individuals often become wheelchair dependent. While intra- and interfamilial phenotypic variability is high, SPG8 is typically more severe than other types of hereditary spastic paraplegia. [from GeneReviews]
Authors:
Inge A Meijer  |  Paul N Valdmanis  |  Guy A Rouleau   view full author information

Additional descriptions

From OMIM
Spastic paraplegia-8 is an autosomal dominant neurologic disorder characterized by adult onset of progressive lower limb spasticity and hyperreflexia resulting in difficulty walking. Some patients may become wheelchair-bound after several decades. Other features may include upper limb spasticity, impaired vibration sense in the distal lower limbs, and urinary urgency or incontinence (summary by de Bot et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).  http://www.omim.org/entry/603563
From MedlinePlus Genetics
People with spastic paraplegia type 8 have spasticity and weakness of the leg muscles. Affected individuals may also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, and reduced bladder control. The signs and symptoms of spastic paraplegia type 8 can begin in childhood, although they typically appear in early to mid-adulthood. 

People with spastic paraplegia type 8 tend to be more severely affected than those with other types of hereditary spastic paraplegias; affected individuals typically require wheelchair assistance in adulthood. However, the signs and symptoms of spastic paraplegia type 8 can vary, even among members of the same family.

Spastic paraplegia type 8 belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and weakness. Hereditary spastic paraplegias are divided into two types: pure and complex. The pure (also called uncomplicated) types involve only the nerves and muscles that control the legs and bladder, whereas the complex (also called complicated) types also involve the nervous system in other parts of the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia.  https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-8

Clinical features

From HPO
Low back pain
MedGen UID:
7389
Concept ID:
C0024031
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the lower back.
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
Urge incontinence is the strong, sudden need to urinate.
Urinary bladder sphincter dysfunction
MedGen UID:
334804
Concept ID:
C1843663
Finding
Abnormal function of a sphincter of the urinary bladder.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
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.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Spastic gait
MedGen UID:
115907
Concept ID:
C0231687
Finding
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.
Upper limb spasticity
MedGen UID:
220882
Concept ID:
C1273957
Finding
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Hyperreflexia in upper limbs
MedGen UID:
375112
Concept ID:
C1843175
Finding
Degeneration of the lateral corticospinal tracts
MedGen UID:
375921
Concept ID:
C1846566
Finding
Deterioration of the tissues of the lateral corticospinal tracts.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 8
Follow this link to review classifications for Hereditary spastic paraplegia 8 in Orphanet.

Professional guidelines

PubMed

Bettencourt C, Morris HR, Singleton AB, Hardy J, Houlden H
J Neurol 2013 Sep;260(9):2414-6. Epub 2013 Jul 24 doi: 10.1007/s00415-013-7044-6. PMID: 23881105Free PMC Article

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