SPG51
MCID: SPS152
MIFTS: 40

Spastic Paraplegia 51, Autosomal Recessive (SPG51)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Spastic Paraplegia 51, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 51, Autosomal Recessive:

Name: Spastic Paraplegia 51, Autosomal Recessive 56 52 73 29 13 6 71
Spg51 56 52 73
Severe Intellectual Disability and Progressive Spastic Paraplegia 52 58
Ap4 Deficiency Syndrome 52 58
Spastic Paraplegia 51 52 29
Cerebral Palsy, Spastic Quadriplegic, 4, Formerly; Cpsq4, Formerly 56
Cerebral Palsy, Spastic Quadriplegic, 4, Formerly 56
Autosomal Recessive Spastic Paraplegia 51 52
Cerebral Palsy, Spastic Quadriplegic 4 73
Cpsq4, Formerly 56
Cpsq4 73

Characteristics:

Orphanet epidemiological data:

58
severe intellectual disability and progressive spastic paraplegia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
two families have been reported (as of june 2011)


HPO:

31
spastic paraplegia 51, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spastic Paraplegia 51, Autosomal Recessive

UniProtKB/Swiss-Prot : 73 Spastic paraplegia 51, autosomal recessive: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG51 is a non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest motor and posture impairments often associated with epilepsy and disturbances of cognition, behavior, sensation, and communication.

MalaCards based summary : Spastic Paraplegia 51, Autosomal Recessive, also known as spg51, is related to hereditary spastic paraplegia 51 and ap-4-associated hereditary spastic paraplegia, and has symptoms including seizures An important gene associated with Spastic Paraplegia 51, Autosomal Recessive is AP4E1 (Adaptor Related Protein Complex 4 Subunit Epsilon 1), and among its related pathways/superpathways are Vesicle-mediated transport and Clathrin derived vesicle budding. Related phenotypes are microcephaly and intellectual disability, severe

OMIM : 56 Spastic paraplegia-51 is an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development (summary by Moreno-De-Luca et al., 2011). (613744)

Related Diseases for Spastic Paraplegia 51, Autosomal Recessive

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23, Autosomal Recessive Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Dominant
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Spastic Paraplegia 80, Autosomal Dominant
Spastic Paraplegia 81, Autosomal Recessive Spastic Paraplegia 82, Autosomal Recessive
Hereditary Spastic Paraplegia 23 Hereditary Spastic Paraplegia 30
Hereditary Spastic Paraplegia 51 Hereditary Spastic Paraplegia 72
Hereditary Spastic Paraplegia Spastic Paraplegia 4
Spastic Paraplegia 8 Spastic Paraplegia 11
Spastic Paraplegia 10 Spastic Paraplegia 12
Spastic Paraplegia 13 Spastic Paraplegia 14
Spastic Paraplegia 15 Spastic Paraplegia 16
Spastic Paraplegia 17 Spastic Paraplegia 18
Spastic Paraplegia 19 Spastic Paraplegia 24
Spastic Paraplegia 25 Spastic Paraplegia 26
Spastic Paraplegia 29 Spastic Paraplegia 3
Spastic Paraplegia 32 Spastic Paraplegia 39
Spastic Paraplegia 47 Spastic Paraplegia 5a
Spastic Paraplegia 5b Spastic Paraplegia 6
Spastic Paraplegia 9 Spastic Paraplegia Type 49
Autosomal Recessive Spastic Paraplegia Type 60 Autosomal Recessive Spastic Paraplegia Type 59
Autosomal Recessive Spastic Paraplegia Type 69 Autosomal Recessive Spastic Paraplegia Type 70
Autosomal Recessive Spastic Paraplegia Type 71 Autosomal Recessive Spastic Paraplegia Type 66
Autosomal Recessive Spastic Paraplegia Type 67 Autosomal Dominant Spastic Paraplegia Type 9b

Diseases related to Spastic Paraplegia 51, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(showing 16, show less)
# Related Disease Score Top Affiliating Genes
1 hereditary spastic paraplegia 51 30.6 AP4S1 AP4M1 AP4E1 AP4B1
2 ap-4-associated hereditary spastic paraplegia 30.3 AP4S1 AP4M1 AP4E1 AP4B1
3 autosomal dominant non-syndromic intellectual disability 9 9.7 AP4S1 AP4B1
4 neuropathy, hereditary sensory, type iic 9.6 AP4E1 AP4B1
5 hermansky-pudlak syndrome 2 9.4 AP4M1 AP4E1
6 spastic paraplegia 32, autosomal recessive 9.4 AP4S1 AP4E1 AP4B1
7 spastic paraplegia 53, autosomal recessive 9.3 AP4S1 AP4E1 AP4B1
8 stuttering 9.2 AP4M1 AP4E1
9 hypertonia 9.1 AP4S1 AP4M1 AP4B1
10 hereditary spastic paraplegia 8.8 AP4S1 AP4M1 AP4E1 AP4B1
11 paraplegia 8.8 AP4S1 AP4M1 AP4E1 AP4B1
12 spastic paraplegia 52, autosomal recessive 8.8 AP4S1 AP4M1 AP4E1 AP4B1
13 spastic paraplegia 50, autosomal recessive 8.8 AP4S1 AP4M1 AP4E1 AP4B1
14 spastic paraplegia 47, autosomal recessive 8.8 AP4S1 AP4M1 AP4E1 AP4B1
15 quadriplegia 8.8 AP4S1 AP4M1 AP4E1 AP4B1
16 cerebral palsy 8.7 AP4S1 AP4M1 AP4E1 AP4B1

Graphical network of the top 20 diseases related to Spastic Paraplegia 51, Autosomal Recessive:



Diseases related to Spastic Paraplegia 51, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 51, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 51, Autosomal Recessive:

58 31 (showing 52, show less)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
2 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
3 progressive spastic paraplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0007020
4 coarse facial features 58 31 frequent (33%) Frequent (79-30%) HP:0000280
5 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
6 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
7 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
8 waddling gait 58 31 frequent (33%) Frequent (79-30%) HP:0002515
9 cerebral cortical atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002120
10 bulbous nose 58 31 frequent (33%) Frequent (79-30%) HP:0000414
11 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
12 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
13 cerebellar atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001272
14 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
15 poor speech 58 31 frequent (33%) Frequent (79-30%) HP:0002465
16 drooling 58 31 frequent (33%) Frequent (79-30%) HP:0002307
17 facial hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0000297
18 spastic dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0002464
19 pes planus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001763
20 stereotypy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000733
21 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
22 wide mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000154
23 short philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000322
24 everted upper lip vermilion 58 31 occasional (7.5%) Occasional (29-5%) HP:0010803
25 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
26 abnormality of the periventricular white matter 58 31 occasional (7.5%) Occasional (29-5%) HP:0002518
27 narrow forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000341
28 shyness 58 31 occasional (7.5%) Occasional (29-5%) HP:0100962
29 overweight 58 31 occasional (7.5%) Occasional (29-5%) HP:0025502
30 seizure 31 occasional (7.5%) HP:0001250
31 strabismus 58 31 very rare (1%) Very rare (<4-1%) HP:0000486
32 genu recurvatum 58 31 very rare (1%) Very rare (<4-1%) HP:0002816
33 amblyopia 58 31 very rare (1%) Very rare (<4-1%) HP:0000646
34 generalized joint laxity 58 31 very rare (1%) Very rare (<4-1%) HP:0002761
35 acetabular dysplasia 58 31 very rare (1%) Very rare (<4-1%) HP:0008807
36 muscular hypotonia 58 Very frequent (99-80%)
37 wide nasal bridge 31 HP:0000431
38 seizures 58 Occasional (29-5%)
39 neonatal hypotonia 31 HP:0001319
40 flexion contracture 31 HP:0001371
41 spasticity 58 Frequent (79-30%)
42 spastic tetraplegia 31 HP:0002510
43 decreased muscle mass 31 HP:0003199
44 nystagmus 31 HP:0000639
45 talipes equinovarus 31 HP:0001762
46 narrow face 31 HP:0000275
47 downslanted palpebral fissures 31 HP:0000494
48 ventriculomegaly 31 HP:0002119
49 pointed chin 31 HP:0000307
50 spastic paraplegia 31 HP:0001258
51 long nose 31 HP:0003189
52 prominent antihelix 31 HP:0000395

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Face:
coarse facial features
short philtrum
facial hypotonia
bitemporal narrowing
long narrow face
more
Neurologic Central Nervous System:
seizures
hyperreflexia
cerebellar atrophy
enlarged ventricles
extensor plantar responses
more
Growth Height:
short stature

Skeletal Feet:
talipes equinovarus

Head And Neck Ears:
prominent antihelix

Neurologic Behavioral Psychiatric Manifestations:
shy behavior
stereotypic laughter
amicable behavior

Head And Neck Nose:
wide nasal bridge
bulbous nose
long nose

Head And Neck Head:
microcephaly

Head And Neck Eyes:
nystagmus
downslanting palpebral fissures

Head And Neck Mouth:
wide mouth
drooling

Skeletal:
joint contractures

Muscle Soft Tissue:
hypotonia, neonatal and later
decreased muscle mass in the thighs

Clinical features from OMIM:

613744

UMLS symptoms related to Spastic Paraplegia 51, Autosomal Recessive:


seizures

Drugs & Therapeutics for Spastic Paraplegia 51, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 51, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 51, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 51, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 51, Autosomal Recessive 29 AP4E1
2 Spastic Paraplegia 51 29

Anatomical Context for Spastic Paraplegia 51, Autosomal Recessive

Publications for Spastic Paraplegia 51, Autosomal Recessive

Articles related to Spastic Paraplegia 51, Autosomal Recessive:

(showing 14, show less)
# Title Authors PMID Year
1
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 6 56
21937992 2011
2
Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. 6 56
21620353 2011
3
Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. 6 56
20972249 2011
4
AP-4-Associated Hereditary Spastic Paraplegia 6
30543385 2018
5
Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly. 6
25552650 2015
6
An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome. 6
24781758 2015
7
Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features. 6
24700674 2014
8
Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) . 6
22290197 2012
9
Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. 6
19559397 2009
10
Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. 6
15037681 2004
11
Hereditary Spastic Paraplegia Overview 6
20301682 2000
12
Adaptor protein complex 4 deficiency: a paradigm of childhood-onset hereditary spastic paraplegia caused by defective protein trafficking. 61
31915823 2020
13
Generation and characterization of six human induced pluripotent stem cell lines (iPSC) from three families with AP4B1-associated hereditary spastic paraplegia (SPG47). 61
31525725 2019
14
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. 61
23897027 2013

Variations for Spastic Paraplegia 51, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 51, Autosomal Recessive:

6 (showing 9, show less) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AP4E1 NC_000015.10:g.50755991_50948682deldeletion Pathogenic 30659 15:51048188-51240879 15:50755991-50948682
2 AP4E1 AP4E1, 4-BP DEL, IVS5DS, 542+1GTAAdeletion Pathogenic 30660
3 AP4E1 AP4E1, VAL454FSinsertion Pathogenic 30661
4 AP4E1 NM_007347.5(AP4E1):c.1317-2A>CSNV Likely pathogenic 635026 rs1567230528 15:51242021-51242021 15:50949824-50949824
5 AP4E1 NM_007347.5(AP4E1):c.2149C>T (p.Pro717Ser)SNV Uncertain significance 458249 rs150743968 15:51285625-51285625 15:50993428-50993428
6 AP4E1 NM_007347.5(AP4E1):c.613C>A (p.His205Asn)SNV Uncertain significance 128402 rs148499164 15:51221276-51221276 15:50929079-50929079
7 AP4E1 NM_007347.5(AP4E1):c.222+18G>ASNV Benign 380768 rs1147129 15:51204364-51204364 15:50912167-50912167
8 AP4E1 NM_007347.5(AP4E1):c.3387G>A (p.Gln1129=)SNV Benign 128400 rs3825798 15:51294832-51294832 15:51002635-51002635
9 AP4E1 NM_007347.5(AP4E1):c.487T>C (p.Cys163Arg)SNV Benign 128401 rs2306331 15:51217361-51217361 15:50925164-50925164

Expression for Spastic Paraplegia 51, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 51, Autosomal Recessive.

Pathways for Spastic Paraplegia 51, Autosomal Recessive

Pathways related to Spastic Paraplegia 51, Autosomal Recessive according to GeneCards Suite gene sharing:

(showing 3, show less)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.56 AP4S1 AP4M1 AP4E1 AP4B1
2
Show member pathways
11.64 AP4S1 AP4M1 AP4E1 AP4B1
3 11.03 AP4S1 AP4M1 AP4E1 AP4B1

GO Terms for Spastic Paraplegia 51, Autosomal Recessive

Cellular components related to Spastic Paraplegia 51, Autosomal Recessive according to GeneCards Suite gene sharing:

(showing 7, show less)
# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.62 AP4S1 AP4M1 AP4E1 AP4B1
2 trans-Golgi network membrane GO:0032588 9.46 AP4S1 AP4M1 AP4E1 AP4B1
3 trans-Golgi network GO:0005802 9.4 AP4M1 AP4B1
4 membrane coat GO:0030117 9.37 AP4E1 AP4B1
5 clathrin adaptor complex GO:0030131 9.26 AP4M1 AP4B1
6 endosome lumen GO:0031904 9.26 AP4S1 AP4M1 AP4E1 AP4B1
7 AP-4 adaptor complex GO:0030124 8.92 AP4S1 AP4M1 AP4E1 AP4B1

Biological processes related to Spastic Paraplegia 51, Autosomal Recessive according to GeneCards Suite gene sharing:

(showing 5, show less)
# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.62 AP4S1 AP4M1 AP4E1 AP4B1
2 intracellular protein transport GO:0006886 9.56 AP4S1 AP4M1 AP4E1 AP4B1
3 vesicle-mediated transport GO:0016192 9.46 AP4S1 AP4M1 AP4E1 AP4B1
4 protein localization GO:0008104 9.26 AP4S1 AP4M1 AP4E1 AP4B1
5 protein targeting GO:0006605 8.92 AP4S1 AP4M1 AP4E1 AP4B1

Sources for Spastic Paraplegia 51, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
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43 MeSH
44 MESH via Orphanet
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50 NDF-RT
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57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
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70 Tocris
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72 UMLS via Orphanet
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