MCID: SLT014
MIFTS: 37

Salt and Pepper Developmental Regression Syndrome

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Skin diseases, Metabolic diseases, Mental diseases

Aliases & Classifications for Salt and Pepper Developmental Regression Syndrome

MalaCards integrated aliases for Salt and Pepper Developmental Regression Syndrome:

Name: Salt and Pepper Developmental Regression Syndrome 57 75
Amish Infantile Epilepsy Syndrome 57 53 25 59 75 37 29 13 6 73
Gm3 Synthase Deficiency 57 53 25 75
Epilepsy Syndrome, Infantile-Onset Symptomatic 57 53 25
Salt and Pepper Mental Retardation Syndrome 57 75
Spdrs 57 75
Infantile-Onset Symptomatic Epilepsy Syndrome-Developmental Stagnation-Blindness Syndrome 59
Infantile-Onset Symptomatic Epilepsy Syndrome - Developmental Stagnation - Blindness 53
Infantile-Onset Symptomatic Epilepsy Syndrome 25
Epilepsy Syndrome Infantile-Onset Symptomatic 75
Ganglioside Gm3 Synthase Deficiency 25
Epilepsy, Infantile, Amish Syndrome 40
Salt-and-Pepper Syndrome 59
St3gal5-Cdg 53
Aies 75

Characteristics:

Orphanet epidemiological data:

59
amish infantile epilepsy syndrome
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;
salt-and-pepper syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in early infancy, between 2 weeks and 3 months
old order amish, african american, french, and korean patients have been described
hyperpigmented skin macules appear after age 3 years and increase in frequency with age


HPO:

32
salt and pepper developmental regression syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Salt and Pepper Developmental Regression Syndrome

NIH Rare Diseases : 53 GM3 synthase deficiency is a rare neurological disorder in which the brain does not develop normally. Symptoms of the disease begin within the first weeks or months of life and include difficulty feeding, irritability, vomiting, and seizures accompanied by loss of consciousness (grand mal seizures). Vision and hearing loss, spots of darker skin color (hyperpigmentation), and intellectual and developmental delays develop as the disease progresses. GM3 synthase deficiency is a congenital disorder of glycosylation and includes both cases described as Amish infantile epilepsysyndrome and cases described as salt & pepper syndrome. GM3 synthase deficiency is caused by a mutation in the ST3GAL5 gene and is inherited in an autosomal recessive manner. The ST3GAL5 gene tells the body to make an enzyme that supports gangliosides, which are molecules that are important for brain development and function. GM3 synthase deficiency is suspected when a child presents with symptoms characteristic of the disease. Genetic testing confirms the diagnosis. Treatment is focused on relieving symptoms of the disease, which may include nutritional and feeding support and medications to lessen the severity of seizures. Although there is no cure for the condition, children with GM3 synthase deficiency have lived into early adulthood.

MalaCards based summary : Salt and Pepper Developmental Regression Syndrome, also known as amish infantile epilepsy syndrome, is related to salt and pepper syndrome and androgen insensitivity syndrome, and has symptoms including vomiting and unspecified visual loss. An important gene associated with Salt and Pepper Developmental Regression Syndrome is ST3GAL5 (ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5), and among its related pathways/superpathways is Glycosphingolipid biosynthesis - ganglio series. Affiliated tissues include skin, brain and testes, and related phenotypes are microcephaly and hearing impairment

Genetics Home Reference : 25 GM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first few weeks after birth, affected infants become irritable and develop feeding difficulties and vomiting that prevent them from growing and gaining weight at the usual rate. Seizures begin within the first year of life and worsen over time. Multiple types of seizures are possible, including generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Some affected children also experience prolonged episodes of seizure activity called nonconvulsive status epilepticus. The seizures associated with GM3 synthase deficiency tend to be resistant (refractory) to treatment with antiseizure medications.

OMIM : 57 Salt and pepper developmental regression syndrome, also known as Amish infantile epilepsy syndrome, is an autosomal recessive neurocutaneous disorder characterized by infantile onset of refractory and recurrent seizures associated with profoundly delayed psychomotor development and/or developmental regression as well as abnormal movements and visual loss (summary by Fragaki et al., 2013). Affected individuals develop hypo- or hyperpigmented skin macules on the trunk, face, and extremities in early childhood (summary by Boccuto et al., 2014). Not all patients have overt seizures (Lee et al., 2016). (609056)

CDC : 3 Español: Norovirus

UniProtKB/Swiss-Prot : 75 Salt and pepper developmental regression syndrome: A rare autosomal recessive disorder characterized by infantile onset of severe, recurrent and refractory seizures, failure to thrive, psychomotor delay, developmental stagnation, and cortical blindness. Deafness is observed in some patients. Affected individuals have patches of skin hypo- or hyperpigmentation on the trunk, face, and extremities.

Related Diseases for Salt and Pepper Developmental Regression Syndrome

Diseases related to Salt and Pepper Developmental Regression Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 144)
# Related Disease Score Top Affiliating Genes
1 salt and pepper syndrome 12.4
2 androgen insensitivity syndrome 11.9
3 amelogenesis imperfecta 11.8
4 autoimmune inner ear disease 11.8
5 aland island eye disease 11.7
6 scoliosis, isolated 1 11.4
7 hereditary amyloidosis 11.2
8 aortic valve insufficiency 11.1
9 childhood-onset cerebral x-linked adrenoleukodystrophy 11.1
10 pediatric arterial ischemic stroke 11.0
11 amelogenesis imperfecta, type ib 11.0
12 jalili syndrome 10.8
13 amelogenesis imperfecta, type ie 10.8
14 amelogenesis imperfecta, type ij 10.8
15 alzheimer disease 10.7
16 neuronitis 10.3
17 cerebritis 10.2
18 amyloidosis 10.2
19 aging 10.2
20 adenocarcinoma 10.1
21 dementia 10.1
22 adenocarcinoma in situ 10.1
23 cerebral amyloid angiopathy, cst3-related 10.1
24 arteries, anomalies of 10.1
25 scoliosis 10.1
26 idiopathic scoliosis 10.1
27 coronary artery anomaly 10.0
28 endotheliitis 10.0
29 diabetes mellitus 10.0
30 depression 10.0
31 neuroblastoma 9.9
32 cervicitis 9.9
33 inclusion body myositis 9.9
34 myositis 9.9
35 dysfibrinogenemia 9.9
36 rett syndrome 9.9
37 epilepsy 9.9
38 coronary heart disease 1 9.8
39 myocardial infarction 9.8
40 hepatitis 9.8
41 endocervical adenocarcinoma 9.8
42 heart disease 9.8
43 endocervicitis 9.8
44 creutzfeldt-jakob disease 9.8
45 hyperlipidemia, familial combined 9.8
46 anxiety 9.8
47 afibrinogenemia 9.8
48 breast cancer 9.7
49 hypercholesterolemia, familial 9.7
50 lung cancer 9.7

Graphical network of the top 20 diseases related to Salt and Pepper Developmental Regression Syndrome:



Diseases related to Salt and Pepper Developmental Regression Syndrome

Symptoms & Phenotypes for Salt and Pepper Developmental Regression Syndrome

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Head And Neck Eyes:
optic atrophy
cortical visual impairment
loss of vision
decreased eye contact
eye deviation

Neurologic Behavioral Psychiatric Manifestations:
irritability

Head And Neck Head:
microcephaly (in some patients)

Neurologic Peripheral Nervous System:
hyporeflexia in the upper limbs
hyperreflexia in the lower limbs

Neurologic Central Nervous System:
developmental regression
status epilepticus
hypotonia
delayed psychomotor development
diffuse brain atrophy
more
Abdomen Gastrointestinal:
vomiting
poor feeding

Head And Neck Ears:
deafness (in some patients)

Skin Nails Hair Skin:
dyspigmentation
hyperpigmented 2 to 5-mm macules mainly on the extremities
de- or hypo-pigmented macules (less common)


Clinical features from OMIM:

609056

Human phenotypes related to Salt and Pepper Developmental Regression Syndrome:

32 (show all 23)
# Description HPO Frequency HPO Source Accession
1 microcephaly 32 occasional (7.5%) HP:0000252
2 hearing impairment 32 occasional (7.5%) HP:0000365
3 visual loss 32 HP:0000572
4 optic atrophy 32 HP:0000648
5 irritability 32 HP:0000737
6 hypermelanotic macule 32 HP:0001034
7 muscular hypotonia 32 HP:0001252
8 global developmental delay 32 HP:0001263
9 choreoathetosis 32 HP:0001266
10 generalized hypotonia 32 HP:0001290
11 myoclonus 32 HP:0001336
12 absent speech 32 HP:0001344
13 failure to thrive 32 HP:0001508
14 vomiting 32 HP:0002013
15 generalized tonic-clonic seizures 32 HP:0002069
16 status epilepticus 32 HP:0002133
17 global brain atrophy 32 HP:0002283
18 developmental regression 32 HP:0002376
19 lower limb hyperreflexia 32 HP:0002395
20 developmental stagnation at onset of seizures 32 HP:0006834
21 feeding difficulties in infancy 32 HP:0008872
22 hyporeflexia of upper limbs 32 HP:0012391
23 cortical visual impairment 32 HP:0100704

UMLS symptoms related to Salt and Pepper Developmental Regression Syndrome:


vomiting, unspecified visual loss

Drugs & Therapeutics for Salt and Pepper Developmental Regression Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Oral Supplementation of Gangliosides to Treat a Rare Metabolic Disorder Enrolling by invitation NCT02234024 Not Applicable

Search NIH Clinical Center for Salt and Pepper Developmental Regression Syndrome

Genetic Tests for Salt and Pepper Developmental Regression Syndrome

Genetic tests related to Salt and Pepper Developmental Regression Syndrome:

# Genetic test Affiliating Genes
1 Amish Infantile Epilepsy Syndrome 29 ST3GAL5

Anatomical Context for Salt and Pepper Developmental Regression Syndrome

MalaCards organs/tissues related to Salt and Pepper Developmental Regression Syndrome:

41
Skin, Brain, Testes, Eye

Publications for Salt and Pepper Developmental Regression Syndrome

Articles related to Salt and Pepper Developmental Regression Syndrome:

# Title Authors Year
1
Early growth and development impairments in patients with ganglioside GM3 synthase deficiency. ( 26649472 )
2016
2
GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype. ( 27232954 )
2016
3
Cutaneous dyspigmentation in patients with ganglioside GM3 synthase deficiency. ( 23436467 )
2013
4
Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency. ( 22990144 )
2013
5
Ganglioside depletion and EGF responses of human GM3 synthase-deficient fibroblasts. ( 18480157 )
2008
6
Etiology of vision loss in ganglioside GM3 synthase deficiency. ( 17050284 )
2006

Variations for Salt and Pepper Developmental Regression Syndrome

ClinVar genetic disease variations for Salt and Pepper Developmental Regression Syndrome:

6
(show top 50) (show all 104)
# Gene Variation Type Significance SNP ID Assembly Location
1 ST3GAL5 NM_003896.3(ST3GAL5): c.862C> T (p.Arg288Ter) single nucleotide variant Pathogenic rs104893668 GRCh37 Chromosome 2, 86071665: 86071665
2 ST3GAL5 NM_003896.3(ST3GAL5): c.862C> T (p.Arg288Ter) single nucleotide variant Pathogenic rs104893668 GRCh38 Chromosome 2, 85844542: 85844542
3 ST3GAL5 NM_003896.3(ST3GAL5): c.1063G> A (p.Glu355Lys) single nucleotide variant Pathogenic rs534438354 GRCh37 Chromosome 2, 86067461: 86067461
4 ST3GAL5 NM_003896.3(ST3GAL5): c.1063G> A (p.Glu355Lys) single nucleotide variant Pathogenic rs534438354 GRCh38 Chromosome 2, 85840338: 85840338
5 ST3GAL5 NM_003896.3(ST3GAL5): c.37C> T (p.Pro13Ser) single nucleotide variant Benign/Likely benign rs559756386 GRCh37 Chromosome 2, 86115992: 86115992
6 ST3GAL5 NM_003896.3(ST3GAL5): c.37C> T (p.Pro13Ser) single nucleotide variant Benign/Likely benign rs559756386 GRCh38 Chromosome 2, 85888869: 85888869
7 ST3GAL5 NM_003896.3(ST3GAL5): c.648C> T (p.Phe216=) single nucleotide variant Conflicting interpretations of pathogenicity rs149309844 GRCh37 Chromosome 2, 86074998: 86074998
8 ST3GAL5 NM_003896.3(ST3GAL5): c.648C> T (p.Phe216=) single nucleotide variant Conflicting interpretations of pathogenicity rs149309844 GRCh38 Chromosome 2, 85847875: 85847875
9 ST3GAL5 NM_003896.3(ST3GAL5): c.1212G> A (p.Glu404=) single nucleotide variant Conflicting interpretations of pathogenicity rs148195895 GRCh37 Chromosome 2, 86067312: 86067312
10 ST3GAL5 NM_003896.3(ST3GAL5): c.1212G> A (p.Glu404=) single nucleotide variant Conflicting interpretations of pathogenicity rs148195895 GRCh38 Chromosome 2, 85840189: 85840189
11 ST3GAL5 NM_003896.3(ST3GAL5): c.1247G> T (p.Arg416Leu) single nucleotide variant Uncertain significance rs200683924 GRCh37 Chromosome 2, 86067277: 86067277
12 ST3GAL5 NM_003896.3(ST3GAL5): c.1247G> T (p.Arg416Leu) single nucleotide variant Uncertain significance rs200683924 GRCh38 Chromosome 2, 85840154: 85840154
13 ST3GAL5 NM_003896.3(ST3GAL5): c.850-5C> T single nucleotide variant Benign rs113976691 GRCh37 Chromosome 2, 86071682: 86071682
14 ST3GAL5 NM_003896.3(ST3GAL5): c.850-5C> T single nucleotide variant Benign rs113976691 GRCh38 Chromosome 2, 85844559: 85844559
15 ST3GAL5 NM_003896.3(ST3GAL5): c.82+1G> C single nucleotide variant Likely pathogenic rs878854615 GRCh37 Chromosome 2, 86115946: 86115946
16 ST3GAL5 NM_003896.3(ST3GAL5): c.82+1G> C single nucleotide variant Likely pathogenic rs878854615 GRCh38 Chromosome 2, 85888823: 85888823
17 ST3GAL5 NM_003896.3(ST3GAL5): c.584G> C (p.Cys195Ser) single nucleotide variant Pathogenic rs886037930 GRCh38 Chromosome 2, 85847939: 85847939
18 ST3GAL5 NM_003896.3(ST3GAL5): c.584G> C (p.Cys195Ser) single nucleotide variant Pathogenic rs886037930 GRCh37 Chromosome 2, 86075062: 86075062
19 ST3GAL5 NM_003896.3(ST3GAL5): c.601G> A (p.Gly201Arg) single nucleotide variant Pathogenic rs771732955 GRCh38 Chromosome 2, 85847922: 85847922
20 ST3GAL5 NM_003896.3(ST3GAL5): c.601G> A (p.Gly201Arg) single nucleotide variant Pathogenic rs771732955 GRCh37 Chromosome 2, 86075045: 86075045
21 ST3GAL5 NM_003896.3(ST3GAL5): c.465G> A (p.Glu155=) single nucleotide variant Conflicting interpretations of pathogenicity rs199590656 GRCh37 Chromosome 2, 86075181: 86075181
22 ST3GAL5 NM_003896.3(ST3GAL5): c.465G> A (p.Glu155=) single nucleotide variant Conflicting interpretations of pathogenicity rs199590656 GRCh38 Chromosome 2, 85848058: 85848058
23 ST3GAL5 NM_003896.3(ST3GAL5): c.*976G> T single nucleotide variant Uncertain significance rs775357214 GRCh37 Chromosome 2, 86066291: 86066291
24 ST3GAL5 NM_003896.3(ST3GAL5): c.*976G> T single nucleotide variant Uncertain significance rs775357214 GRCh38 Chromosome 2, 85839168: 85839168
25 ST3GAL5 NM_003896.3(ST3GAL5): c.*678C> T single nucleotide variant Uncertain significance rs188807604 GRCh37 Chromosome 2, 86066589: 86066589
26 ST3GAL5 NM_003896.3(ST3GAL5): c.*678C> T single nucleotide variant Uncertain significance rs188807604 GRCh38 Chromosome 2, 85839466: 85839466
27 ST3GAL5 NM_003896.3(ST3GAL5): c.*594G> A single nucleotide variant Uncertain significance rs116456890 GRCh37 Chromosome 2, 86066673: 86066673
28 ST3GAL5 NM_003896.3(ST3GAL5): c.*594G> A single nucleotide variant Uncertain significance rs116456890 GRCh38 Chromosome 2, 85839550: 85839550
29 ST3GAL5 NM_003896.3(ST3GAL5): c.*355G> A single nucleotide variant Uncertain significance rs573408903 GRCh37 Chromosome 2, 86066912: 86066912
30 ST3GAL5 NM_003896.3(ST3GAL5): c.*355G> A single nucleotide variant Uncertain significance rs573408903 GRCh38 Chromosome 2, 85839789: 85839789
31 ST3GAL5 NM_003896.3(ST3GAL5): c.*140delA deletion Uncertain significance rs550737011 GRCh37 Chromosome 2, 86067127: 86067127
32 ST3GAL5 NM_003896.3(ST3GAL5): c.*140delA deletion Uncertain significance rs550737011 GRCh38 Chromosome 2, 85840004: 85840004
33 ST3GAL5 NM_003896.3(ST3GAL5): c.*115C> T single nucleotide variant Uncertain significance rs193077813 GRCh37 Chromosome 2, 86067152: 86067152
34 ST3GAL5 NM_003896.3(ST3GAL5): c.*115C> T single nucleotide variant Uncertain significance rs193077813 GRCh38 Chromosome 2, 85840029: 85840029
35 ST3GAL5 NM_003896.3(ST3GAL5): c.1036G> A (p.Val346Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs145738225 GRCh37 Chromosome 2, 86067488: 86067488
36 ST3GAL5 NM_003896.3(ST3GAL5): c.1036G> A (p.Val346Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs145738225 GRCh38 Chromosome 2, 85840365: 85840365
37 ST3GAL5 NM_003896.3(ST3GAL5): c.415G> T (p.Val139Leu) single nucleotide variant Uncertain significance rs377046345 GRCh38 Chromosome 2, 85848108: 85848108
38 ST3GAL5 NM_003896.3(ST3GAL5): c.415G> T (p.Val139Leu) single nucleotide variant Uncertain significance rs377046345 GRCh37 Chromosome 2, 86075231: 86075231
39 ST3GAL5 NM_003896.3(ST3GAL5): c.84A> C (p.Ala28=) single nucleotide variant Uncertain significance rs530496667 GRCh38 Chromosome 2, 85863484: 85863484
40 ST3GAL5 NM_003896.3(ST3GAL5): c.84A> C (p.Ala28=) single nucleotide variant Uncertain significance rs530496667 GRCh37 Chromosome 2, 86090607: 86090607
41 ST3GAL5 NM_003896.3(ST3GAL5): c.-91G> A single nucleotide variant Uncertain significance rs879798501 GRCh38 Chromosome 2, 85888996: 85888996
42 ST3GAL5 NM_003896.3(ST3GAL5): c.-91G> A single nucleotide variant Uncertain significance rs879798501 GRCh37 Chromosome 2, 86116119: 86116119
43 ST3GAL5 NM_003896.3(ST3GAL5): c.*607C> T single nucleotide variant Uncertain significance rs535114385 GRCh37 Chromosome 2, 86066660: 86066660
44 ST3GAL5 NM_003896.3(ST3GAL5): c.*607C> T single nucleotide variant Uncertain significance rs535114385 GRCh38 Chromosome 2, 85839537: 85839537
45 ST3GAL5 NM_003896.3(ST3GAL5): c.*455G> A single nucleotide variant Uncertain significance rs886056388 GRCh37 Chromosome 2, 86066812: 86066812
46 ST3GAL5 NM_003896.3(ST3GAL5): c.*455G> A single nucleotide variant Uncertain significance rs886056388 GRCh38 Chromosome 2, 85839689: 85839689
47 ST3GAL5 NM_003896.3(ST3GAL5): c.*363A> C single nucleotide variant Uncertain significance rs886056389 GRCh37 Chromosome 2, 86066904: 86066904
48 ST3GAL5 NM_003896.3(ST3GAL5): c.*363A> C single nucleotide variant Uncertain significance rs886056389 GRCh38 Chromosome 2, 85839781: 85839781
49 ST3GAL5 NM_003896.3(ST3GAL5): c.*69A> G single nucleotide variant Uncertain significance rs886056391 GRCh37 Chromosome 2, 86067198: 86067198
50 ST3GAL5 NM_003896.3(ST3GAL5): c.*69A> G single nucleotide variant Uncertain significance rs886056391 GRCh38 Chromosome 2, 85840075: 85840075

Expression for Salt and Pepper Developmental Regression Syndrome

Search GEO for disease gene expression data for Salt and Pepper Developmental Regression Syndrome.

Pathways for Salt and Pepper Developmental Regression Syndrome

Pathways related to Salt and Pepper Developmental Regression Syndrome according to KEGG:

37
# Name Kegg Source Accession
1 Glycosphingolipid biosynthesis - ganglio series hsa00604

GO Terms for Salt and Pepper Developmental Regression Syndrome

Sources for Salt and Pepper Developmental Regression Syndrome

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7 CNVD
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10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
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74 UMLS via Orphanet
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