Autosomal recessive spastic paraplegia type 15

General Information (adopted from Orphanet):

Synonyms, Signs: SPG15
Spastic paraplegia - retinal degeneration
Hereditary spastic paraparesis type 15
Spastic paraplegia and retinal degeneration
Kjellin syndrome
Number of Symptoms 33
OrphanetNr: 100996
OMIM Id: 270700
ICD-10: G11.4
UMLs: C1849128
MeSH: C536642
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 10 families [Orphanet]
Inheritance: Autosomal recessive
18332254; 22554690 [IBIS]
Age of onset: Adolescent
18332254 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal recessive complex spastic paraplegia
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by slowly progressive spasticity of the lower extremities. Pathologically, HSP is characterized by axonal degeneration in the long descending and ascending tracts of the spinal cord, especially in their terminal portions. Autosomal recessive HSP-TCC (e.g. SPG15, SPG11) is characterized clinically by slowly progressive spastic paraparesis and mental deterioration that begins mainly in the second decade of life. The neurological and radiological findings in SPG11 and SPG15 patients were relatively similar (PMID:18332254). SPG15 and SPG11 are accessory proteins of the AP5 complex of sorting of vesicles, putatively involved in endosomal trafficking. SPG15 is due to mutations in the ZFYVE26 gene which encodes a zinc-finger protein with a FYVE domain, called spastizin. Spastizin is expressed in the same tissues as spatacsin (SPG11) and partially co-localises with microtubules, mitochondria and the nucleus. Spastizin is also detected at the midbody during cytokinesis. The protein interacts with spatacsin and with KIAA0415 (SPG48), a member of the AP5 complex. SPG15 is the second most common cause of SPG with TCC (thin corpus callosum). It shows an early-onset (first to second decade) (PMID:22554690, 23825025).

Symptom Information: Sort by abundance 

1
 (HPO:0000608) Macular degeneration 22554690 IBIS 36 / 7739
2
 (HPO:0000580) Pigmentary retinopathy 22554690 IBIS 49 / 7739
3
 (HPO:0000546) Retinal degeneration 3/7 [HPO:probinson] 19805727 IBIS 61 / 7739
4
 (HPO:0000639) Nystagmus 4/10 [HPO:probinson] 19805727 IBIS 555 / 7739
5
 (HPO:0003693) Distal amyotrophy 18394578 IBIS 118 / 7739
6
 (HPO:0002169) Clonus 24999486 IBIS 37 / 7739
7
 (HPO:0011448) Ankle clonus 24999486 IBIS 31 / 7739
8
 (HPO:0007340) Lower limb muscle weakness 18332254 IBIS 61 / 7739
9
 (HPO:0003477) Peripheral axonal neuropathy 5/9 [HPO:probinson] 19805727 IBIS 62 / 7739
10
 (HPO:0001271) Polyneuropathy 22554690 IBIS 56 / 7739
11
 (HPO:0002200) Pseudobulbar signs 18332254 IBIS 15 / 7739
12
 (HPO:0003487) Babinski sign 18332254 IBIS 179 / 7739
13
 (HPO:0001347) Hyperreflexia 18332254 IBIS 363 / 7739
14
 (HPO:0001348) Brisk reflexes 18332254 IBIS 15 / 7739
15
 (HPO:0007350) Hyperreflexia in upper limbs 18332254 IBIS 5 / 7739
16
 (HPO:0002395) Lower limb hyperreflexia 18332254 IBIS 26 / 7739
17
 (HPO:0002061) Lower limb spasticity 18332254 IBIS 56 / 7739
18
 (HPO:0001258) Spastic paraplegia 18394578 IBIS 97 / 7739
19
 (HPO:0002064) Spastic gait 24999486 IBIS 46 / 7739
20
 (HPO:0001285) Spastic tetraparesis 22554690 IBIS 29 / 7739
21
 (HPO:0006986) Upper limb spasticity 18332254 IBIS 15 / 7739
22
 (HPO:0001251) Ataxia 24999486 IBIS 413 / 7739
23
 (HPO:0001300) Parkinsonism 22554690 IBIS 75 / 7739
24
 (HPO:0001260) Dysarthria 18332254 IBIS 329 / 7739
25
 (HPO:0001268) Mental deterioration 18332254 IBIS 88 / 7739
26
 (HPO:0001249) Intellectual disability 22554690 IBIS 1089 / 7739
27
 (HPO:0001761) Pes cavus 18332254 IBIS 225 / 7739
28
 (HPO:0002079) Hypoplasia of the corpus callosum 18332254 IBIS 161 / 7739
29
 (HPO:0001317) Abnormality of the cerebellum 22554690 IBIS 36 / 7739
30
 (HPO:0002500) Abnormality of the cerebral white matter 18332254 IBIS 73 / 7739
31
 (HPO:0001272) Cerebellar atrophy 18332254 IBIS 197 / 7739
32
 (HPO:0002059) Cerebral atrophy 18332254 IBIS 171 / 7739
33
 (HPO:0003676) Progressive disorder 24999486 IBIS 148 / 7739

Associated genes:

ZFYVE26;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Spastic paraplegia-15 is an autosomal recessive neurodegenerative disorder characterized by progressive spasticity primarily affecting the lower limbs. It is a complex form of spastic paraplegia, associated with other neurologic dysfunction, including variable mental retardation, hearing and visual defects, ...
Clinical Description OMIM Louis-Bar and Pirot (1945) described 2 brothers with macular degeneration and spastic paraplegia referred to by the authors as 'Strumpell type.' A third brother was said to have a forme fruste of spastic paraplegia. They could find no ...
Molecular genetics OMIM Mannan et al. (2006) failed to identify mutations in the coding or flanking intronic sequences of the RTN1 gene (600865) on chromosome 14q23.1 in 2 index patients from the SPG15 families reported by Hughes et al. (2001). ...
Population genetics OMIM Boukhris et al. (2009) identified a molecular basis for hereditary spastic paraplegia in 13 (34.2%) of 38 unrelated families from southern Tunisia with the disorder. The most common forms of SPG were SPG11 in 7 (18.4%) families and ...