Autosomal dominant spastic paraplegia type 6

General Information (adopted from Orphanet):

Synonyms, Signs: SPG6
FSP3
Familial spastic paraplegia, autosomal dominant, 3
Autosomal dominant familial spastic paraplegia type 3
Number of Symptoms 35
OrphanetNr: 100988
OMIM Id: 600363
ICD-10: G11.4
UMLs: C1838192
MeSH: C536866
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 10 families [Orphanet]
Inheritance: Autosomal dominant
17205300 [IBIS]
Age of onset: Childhood
Adolescent
Adult
17205300 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Pure or complex autosomal dominant spastic paraplegia
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder caused by degeneration of corticospinal axons. Most HSP patients have the same core features characterized by spastic gait, lower limb hypertonicity, hyperreflexia, extensor-plantar responses and muscle weakness. Hereditary spastic paraplegia type 6 (SPG6) is caused by mutations in the NIPA1 gene (FSP3; SPG6).

Symptom Information: Sort by abundance 

1
 (HPO:0000505) Visual impairment Occasional [IBIS] 17% (n=6) 17205300 IBIS 297 / 7739
2
 (HPO:0007210) Lower limb amyotrophy Very frequent [IBIS] 100% (n=5) 21419568 IBIS 7 / 7739
3
 (HPO:0004302) Functional motor problems Very frequent [IBIS] 100% (n=6) 17205300 IBIS 2 / 7739
4
 (HPO:0002169) Clonus 21419568 IBIS 37 / 7739
5
 (HPO:0011448) Ankle clonus Very frequent [IBIS] 100% (n=5) 21419568 IBIS 31 / 7739
6
 (HPO:0011449) Knee clonus Frequent [IBIS] 40% (n=5) 21419568 IBIS 10 / 7739
7
 (HPO:0007340) Lower limb muscle weakness Very frequent [IBIS] 100% (n=5) 21419568 IBIS 61 / 7739
8
 (HPO:0002166) Impaired vibration sensation in the lower limbs Frequent [IBIS] 60% (n=5) 21419568 IBIS 26 / 7739
9
 (HPO:0007108) Demyelinating peripheral neuropathy Frequent [IBIS] 40% (n=5) 21419568 IBIS 8 / 7739
10
 (HPO:0001271) Polyneuropathy 24954637 IBIS 56 / 7739
11
 (HPO:0003487) Babinski sign Frequent [IBIS] 75% (n=4) 17205300 IBIS 179 / 7739
12
 (HPO:0001347) Hyperreflexia Frequent [IBIS] 21419568 IBIS 363 / 7739
13
 (HPO:0007350) Hyperreflexia in upper limbs Frequent [IBIS] 60% (n=5) 21419568 IBIS 5 / 7739
14
 (HPO:0002395) Lower limb hyperreflexia Very frequent [IBIS] 100% (n=6) 17205300 IBIS 26 / 7739
15
 (HPO:0007083) Hyperactive patellar reflex Very frequent [IBIS] 100% (n=5) 21419568 IBIS 4 / 7739
16
 (HPO:0002061) Lower limb spasticity Very frequent [IBIS] 17205300 IBIS 56 / 7739
17
 (HPO:0001258) Spastic paraplegia Very frequent [IBIS] 14508710 IBIS 97 / 7739
18
 (HPO:0002191) Progressive spasticity Very frequent [IBIS] 17205300 IBIS 12 / 7739
19
 (HPO:0002064) Spastic gait Very frequent [IBIS] 100% (n=6) 17205300 IBIS 46 / 7739
20
 (HPO:0006986) Upper limb spasticity 24954637 IBIS 15 / 7739
21
 (HPO:0012179) Craniofacial dystonia 24954637 IBIS 4 / 7739
22
 (HPO:0001260) Dysarthria 24954637 IBIS 329 / 7739
23
 (HPO:0000722) Obsessive-compulsive behavior Occasional [IBIS] 17% (n=6) 17205300 IBIS 35 / 7739
24
 (HPO:0100543) Cognitive impairment 24954637 IBIS 230 / 7739
25
 (HPO:0002354) Memory impairment Frequent [IBIS] 67% (n=6) 17205300 IBIS 63 / 7739
26
 (HPO:0001337) Tremor Occasional [IBIS] Rare [HPO:skoehler] 21% (n=14) 15711826 IBIS 200 / 7739
27
 (HPO:0003438) Absent Achilles reflex Very frequent [IBIS] 100% (n=5) 21419568 IBIS 9 / 7739
28
 (HPO:0001250) Seizures Frequent [IBIS] 36% (n=14) 15711826 IBIS 1245 / 7739
29
 (HPO:0001761) Pes cavus Very frequent [IBIS] 100% (n=5) 21419568 IBIS 225 / 7739
30
 (HPO:0006006) Hypotrophy of the small hand muscles 24954637 IBIS 4 / 7739
31
 (HPO:0100515) Pollakisuria Occasional [IBIS] 17% (n=6) 17205300 IBIS 12 / 7739
32
 (HPO:0000016) Urinary retention Occasional [IBIS] 17% (n=6) 17205300 IBIS 7 / 7739
33
 (HPO:0000012) Urinary urgency Frequent [IBIS] 80% (n=5) 21419568 IBIS 35 / 7739
34
 (HPO:0030237) Hand muscle weakness Frequent [IBIS] 40% (n=5) 21419568 IBIS 4 / 7739
35
 (HPO:0003676) Progressive disorder 17205300 IBIS 148 / 7739

Associated genes:

NIPA1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Fink et al. (1995) reported a family in which hereditary spastic paraplegia had been diagnosed in 31 living subjects. The disorder developed insidiously with progressive gait disturbance at age 12 to 35 years. The unimodal distribution of age ...
Molecular genetics OMIM Rainier et al. (2003) analyzed a large kindred in which autosomal dominant hereditary spastic paraplegia mapped to the SPG6 locus (Fink et al., 1995) and found no evidence of genetic imprinting. Therefore, they analyzed as SPG6 candidates the ...