Autosomal recessive spastic paraplegia type 7

General Information (adopted from Orphanet):

Synonyms, Signs: SPG7
Number of Symptoms 51
OrphanetNr: 99013
OMIM Id: 600146
607259
ICD-10: G11.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: <= 6 of 100 000 - PMID: 20108356 [IBIS]
Inheritance: Monogenic
Autosomal recessive
Sporadic
- PMID: 22266886 [IBIS]
Age of onset: Childhood
Adolescent
Adult
- PMID: 20108356 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal recessive syndromic optic atrophy
 -Rare eye disease
 -Rare genetic disease
Mitochondrial disorder due to a defect in mitochondrial protein synthesis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
Pure or complex autosomal recessive spastic paraplegia
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Hereditary spastic paraplegias (HSPs) are clinically and genetically highly heterogeneous. The autosomal recessive hereditary spastic paraplegia 7 (SPG7) is caused by mutations in the SGP7 gene (= CAR, CMAR, PGN, SPG5C) encoding the mitochondrial AAA metalloproteinase paraplegin. The mutational spectrum comprises missense and nonsense mutations as well as rarer small indels. Additionally, at least studies of two families with large intragenic paraplegin deletions have been published. The phenotype of SPG7 is complicated by mild to moderate cerebellar signs as well as cerebellar atrophy on MRI in the majority of cases. The prevalence of paraplegin mutations in sporadic or autosomal recessive HSP index cases ranges from as low as 1.5% to about 7% (PMID:22266886). Mutations in the SPG7 gene, mapped to Chromosome 16q24.3, are responsible for autosomal recessive HSP (ARHSP) forms leading to both pure and complicated phenotypes. (PMID:20108356). The prevalence of SPG7-HSP is estimated to be around 2 to 6 of 100,000 (PMID:20108356). Onset is usually in adulthood, but ranges between 10–72 years (PMID:24466038).

Symptom Information: Sort by abundance 

1
 (HPO:0000648) Optic atrophy 22266886 IBIS 238 / 7739
2
 (HPO:0000488) Retinopathy 24466038 IBIS 75 / 7739
3
 (HPO:0000590) Progressive external ophthalmoplegia 24727571 IBIS 23 / 7739
4
 (HPO:0000639) Nystagmus 20108356 IBIS 555 / 7739
5
 (HPO:0001488) Bilateral ptosis 20108356 IBIS 42 / 7739
6
 (HPO:0007838) Progressive ptosis 20108356 IBIS 2 / 7739
7
 (HPO:0008972) Decreased activity of mitochondrial respiratory chain Occasional [IBIS] 22266886 IBIS 34 / 7739
8
 (HPO:0011923) Decreased activity of mitochondrial complex I Occasional [IBIS] 22266886 IBIS 35 / 7739
9
 (HPO:0011924) Decreased activity of mitochondrial complex III 24466038 IBIS 22 / 7739
10
 (HPO:0008347) Decreased activity of mitochondrial complex IV 24466038 IBIS 31 / 7739
11
 (HPO:0003200) Ragged-red muscle fibers Occasional [IBIS] 22266886 IBIS 37 / 7739
12
 (HPO:0003202) Skeletal muscle atrophy 24466038 IBIS 281 / 7739
13
 (HPO:0008969) Leg muscle stiffness 20108356 IBIS 5 / 7739
14
 (HPO:0007340) Lower limb muscle weakness Frequent [IBIS] 11377972 IBIS 61 / 7739
15
 (HPO:0003484) Upper limb muscle weakness 24466038 IBIS 19 / 7739
16
 (HPO:0003474) Sensory impairment 20108356 IBIS 54 / 7739
17
 (HPO:0002495) Impaired vibratory sensation 24466038 IBIS 26 / 7739
18
 (HPO:0002166) Impaired vibration sensation in the lower limbs 11377972 IBIS 26 / 7739
19
 (HPO:0009830) Peripheral neuropathy Occasional [IBIS] 22266886 IBIS 206 / 7739
20
 (HPO:0001271) Polyneuropathy 24954637 IBIS 56 / 7739
21
 (HPO:0002066) Gait ataxia 24727571 IBIS 327 / 7739
22
 (HPO:0002070) Limb ataxia 24466038 IBIS 41 / 7739
23
 (HPO:0002497) Spastic ataxia Very frequent [IBIS] 100% (n=9) 20108356 IBIS 13 / 7739
24
 (HPO:0002078) Truncal ataxia 24466038 IBIS 41 / 7739
25
 (HPO:0007256) Abnormal pyramidal signs 20108356 IBIS 116 / 7739
26
 (HPO:0003487) Babinski sign 24466038 IBIS 179 / 7739
27
 (HPO:0001347) Hyperreflexia 20108356 IBIS 363 / 7739
28
 (HPO:0002061) Lower limb spasticity 20108356 IBIS 56 / 7739
29
 (HPO:0002313) Spastic paraparesis 20108356 IBIS 33 / 7739
30
 (HPO:0001258) Spastic paraplegia Very frequent [IBIS] 22266886 IBIS 97 / 7739
31
 (HPO:0002064) Spastic gait 24727571 IBIS 46 / 7739
32
 (HPO:0006986) Upper limb spasticity 24466038 IBIS 15 / 7739
33
 (HPO:0001332) Dystonia 24466038 IBIS 197 / 7739
34
 (HPO:0001260) Dysarthria Frequent [IBIS] 44% (n=9) 24727571 IBIS 329 / 7739
35
 (HPO:0100543) Cognitive impairment 24466038 IBIS 230 / 7739
36
 (MedDRA:10048327) Supranuclear palsy 22266886 IBIS 2 / 7739
37
 (HPO:0002015) Dysphagia 20108356 IBIS 301 / 7739
38
 (HPO:0001761) Pes cavus 24466038 IBIS 225 / 7739
39
 (HPO:0002650) Scoliosis 24466038 IBIS 705 / 7739
40
 (HPO:0007370) Aplasia/Hypoplasia of the corpus callosum 24466038 IBIS 180 / 7739
41
 (HPO:0000492) Abnormality of the eyelid 20108356 IBIS 41 / 7739
42
 (HPO:0002839) Urinary bladder sphincter dysfunction Frequent [IBIS] 33% (n=9) 24727571 IBIS 34 / 7739
43
 (HPO:0000020) Urinary incontinence 24466038 IBIS 75 / 7739
44
 (HPO:0000012) Urinary urgency 24466038 IBIS 35 / 7739
45
 (HPO:0000365) Hearing impairment 24466038 IBIS 539 / 7739
46
 (HPO:0003688) Decreased activity of cytochrome C oxidase in muscle tissue Occasional [IBIS] 22266886 IBIS 20 / 7739
47
 (HPO:0002500) Abnormality of the cerebral white matter 20108356 IBIS 73 / 7739
48
 (HPO:0001273) Abnormality of the corpus callosum 20108356 IBIS 20 / 7739
49
 (HPO:0001272) Cerebellar atrophy Frequent [IBIS] 24466038 IBIS 197 / 7739
50
 (HPO:0002314) Degeneration of the lateral corticospinal tracts 24727571 IBIS 9 / 7739
51
 (MedDRA:10046494) Urge incontinence 24466038 IBIS 2 / 7739

Associated genes:

SPG7;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM De Michele et al. (1998) reported a large consanguineous family with autosomal recessive spastic paraplegia with age of onset between 25 and 42 years (mean 30 +/- 8 years). Abnormal gait was the presenting symptom in all cases, ...
Molecular genetics OMIM Casari et al. (1998) found that all affected individuals from the SPG7 family reported by De Michele et al. (1998) were homozygous for a 9.5-kb deletion (602783.0003) in the SPG7 gene.

In 1 of 2 brothers from ...