SEMDG
MCID: SPN352
MIFTS: 29

Spondyloepimetaphyseal Dysplasia, Genevieve Type (SEMDG)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Spondyloepimetaphyseal Dysplasia, Genevieve Type

MalaCards integrated aliases for Spondyloepimetaphyseal Dysplasia, Genevieve Type:

Name: Spondyloepimetaphyseal Dysplasia, Genevieve Type 57 58 72 29 6
Semdg 57 58 72
Semd, Genevieve Type 57 58
Semd Genevieve Type 20 72
Nans Deficiency 57 72
Dysplasia, Spondyloepimetaphyseal, Camera-Genevieve Type 39
Spondyloepimetaphyseal Dysplasia, Camera-Genevieve Type 57
Spondyloepimetaphyseal Dysplasia, Genevieve-Type 12
Spondyloepimetaphyseal Dysplasia Genevieve Type 20

Characteristics:

Orphanet epidemiological data:

58
spondyloepimetaphyseal dysplasia, genevieve type
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
vertebral bodies appear severely dysplastic in childhood, but have normal shape in adulthood
metaphyseal striations at the knees in childhood disappear in adulthood


HPO:

31
spondyloepimetaphyseal dysplasia, genevieve type:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Spondyloepimetaphyseal Dysplasia, Genevieve Type

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 168454 Definition Spondyloepimetaphyseal dysplasia, Genevieve type is a rare primary bone dysplasia characterized by severe developmental delay and skeletal dysplasia (including short stature, premature carpal ossification, platyspondyly, longitudinal metaphyseal striations, and small epiphyses), as well as moderate to severe intellectual disability and facial dysmorphism, including prominent forehead, mild synophrys, depressed nasal bridge, prominent bulbous nasal tip and full lips.

MalaCards based summary : Spondyloepimetaphyseal Dysplasia, Genevieve Type, is also known as semdg. An important gene associated with Spondyloepimetaphyseal Dysplasia, Genevieve Type is NANS (N-Acetylneuraminate Synthase). The drug Azacitidine has been mentioned in the context of this disorder. Affiliated tissues include bone, and related phenotypes are strabismus and joint laxity

Disease Ontology : 12 A spondyloepimetaphyseal dysplasia that is characterized by infantile-onset severe developmental delay and skeletal dysplasia, including short stature, premature carpal ossification, platyspondyly, longitudinal metaphyseal striations, and small epiphyses and has material basis in homozygous or compound heterozygous mutation in the NANS gene on chromosome 9q22.

OMIM® : 57 Spondyloepiphyseal dysplasia of the Genevieve type (SEMDG) is characterized by infantile-onset severe developmental delay and skeletal dysplasia, including short stature, premature carpal ossification, platyspondyly, longitudinal metaphyseal striations, and small epiphyses (summary by van Karnebeek et al., 2016). (610442) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Spondyloepimetaphyseal dysplasia, Genevieve type: An autosomal recessive disorder characterized by global developmental delay with infantile onset, mental retardation, skeletal dysplasia, and short stature. Skeletal findings include flat vertebral bodies with irregular vertebral plates, irregular and flared metaphyses with vertical striations, small and irregular epiphyses, premature carpal ossification and small carpal bones.

Related Diseases for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Symptoms & Phenotypes for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Human phenotypes related to Spondyloepimetaphyseal Dysplasia, Genevieve Type:

31 (show all 40)
# Description HPO Frequency HPO Source Accession
1 strabismus 31 occasional (7.5%) HP:0000486
2 joint laxity 31 occasional (7.5%) HP:0001388
3 ventriculomegaly 31 occasional (7.5%) HP:0002119
4 hypoplasia of the corpus callosum 31 occasional (7.5%) HP:0002079
5 small basal ganglia 31 occasional (7.5%) HP:0012697
6 seizure 31 occasional (7.5%) HP:0001250
7 intellectual disability 31 HP:0001249
8 nystagmus 31 HP:0000639
9 ataxia 31 HP:0001251
10 short neck 31 HP:0000470
11 coarse facial features 31 HP:0000280
12 microcephaly 31 HP:0000252
13 brachycephaly 31 HP:0000248
14 intellectual disability, severe 31 HP:0010864
15 prominent forehead 31 HP:0011220
16 thick lower lip vermilion 31 HP:0000179
17 low posterior hairline 31 HP:0002162
18 epicanthus 31 HP:0000286
19 platyspondyly 31 HP:0000926
20 low anterior hairline 31 HP:0000294
21 synophrys 31 HP:0000664
22 wide nose 31 HP:0000445
23 narrow iliac wings 31 HP:0002868
24 abnormality of the skin 31 HP:0000951
25 cerebral atrophy 31 HP:0002059
26 hirsutism 31 HP:0001007
27 generalized hypotonia 31 HP:0001290
28 abnormality of the pinna 31 HP:0000377
29 long fibula 31 HP:0003085
30 flat acetabular roof 31 HP:0003180
31 irregular vertebral endplates 31 HP:0003301
32 irregular epiphyses 31 HP:0010582
33 short femoral neck 31 HP:0100864
34 posterior scalloping of vertebral bodies 31 HP:0005121
35 flared metaphysis 31 HP:0003015
36 metaphyseal irregularity 31 HP:0003025
37 spondyloepimetaphyseal dysplasia 31 HP:0002651
38 small epiphyses 31 HP:0010585
39 carpal bone hypoplasia 31 HP:0001498
40 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
nystagmus
synophrys
epicanthal folds
strabismus (in some patients)

Head And Neck Neck:
short neck

Skin Nails Hair Hair:
low posterior hairline
low anterior hairline
synophrys
hirsutism (back and legs)

Skeletal Pelvis:
narrow iliac wings
flat acetabular roofs
short femoral necks

Head And Neck Nose:
broad nose
sunken nasal bridge
prominent bulbous nasal tip

Head And Neck Face:
coarse face

Head And Neck Mouth:
full lips
eversion of lower lip

Head And Neck Teeth:
dental misalignment (in some patients)

Neurologic Central Nervous System:
ataxia
hypotonia
mental retardation, severe
seizures (in some patients)
hypoplastic corpus callosum (in some patients)
more
Head And Neck Head:
microcephaly
brachycephaly
prominent forehead

Skeletal Spine:
platyspondyly
posterior scalloping of vertebral bodies
coronal clefts at birth
irregular vertebral plates

Skeletal:
spondyloepimetaphyseal dysplasia

Head And Neck Ears:
simple ears

Skeletal Limbs:
small, irregular epiphyses
joint laxity (in some patients)
irregular, flared metaphyses
vertical striations of metaphyses
disproportionately long fibula

Skeletal Hands:
small carpals
advanced carpal ossification in childhood

Skin Nails Hair Skin Electron Microscopy:
large number of small vacuoles near cytoplasmic membrane in fibroblasts and macrophages
large vacuoles with either myelinic or granular osmiophilic bodies

Clinical features from OMIM®:

610442 (Updated 05-Apr-2021)

Drugs & Therapeutics for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Drugs for Spondyloepimetaphyseal Dysplasia, Genevieve Type (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Azacitidine Approved, Investigational 320-67-2 9444

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Sialic Acid Supplementation in NANS Deficiency: An Open-label, Proof of Concept, Two-centers Study Completed NCT03545568

Search NIH Clinical Center for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Genetic Tests for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Genetic tests related to Spondyloepimetaphyseal Dysplasia, Genevieve Type:

# Genetic test Affiliating Genes
1 Spondyloepimetaphyseal Dysplasia, Genevieve Type 29 NANS

Anatomical Context for Spondyloepimetaphyseal Dysplasia, Genevieve Type

MalaCards organs/tissues related to Spondyloepimetaphyseal Dysplasia, Genevieve Type:

40
Bone

Publications for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Articles related to Spondyloepimetaphyseal Dysplasia, Genevieve Type:

# Title Authors PMID Year
1
NANS-mediated synthesis of sialic acid is required for brain and skeletal development. 6 57
27213289 2016
2
Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation. 57 6
15726110 2005
3
Sponastrime dysplasia: report on two siblings with metal retardation. 57 6
8152878 1993
4
Sponastrime dysplasia: five new cases and review of nine previously published cases. 57
8723082 1996
5
Heterogeneity of SPONASTRIME dysplasia: delineation of a variant form with severe mental retardation. 57
7551156 1995
6
[Using repeated measurement of 'analysis of variance' on hypertension patients to evaluate the self-management program in the communities]. 61
19173846 2008

Variations for Spondyloepimetaphyseal Dysplasia, Genevieve Type

ClinVar genetic disease variations for Spondyloepimetaphyseal Dysplasia, Genevieve Type:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NANS , TRIM14 NM_018946.4(NANS):c.449-10_449-5delinsATGG Indel Pathogenic 235184 rs879255602 GRCh37: 9:100840465-100840470
GRCh38: 9:98078183-98078188
2 NANS , TRIM14 NM_018946.4(NANS):c.562T>C (p.Tyr188His) SNV Pathogenic 235190 rs878852981 GRCh37: 9:100840588-100840588
GRCh38: 9:98078306-98078306
3 NANS , TRIM14 NM_018946.4(NANS):c.452G>A (p.Arg151His) SNV Pathogenic 235187 rs140402727 GRCh37: 9:100840478-100840478
GRCh38: 9:98078196-98078196
4 NANS , TRIM14 NM_018946.4(NANS):c.389dup (p.Lys131fs) Duplication Pathogenic 235185 rs878853267 GRCh37: 9:100839235-100839236
GRCh38: 9:98076953-98076954
5 NANS , TRIM14 NM_018946.4(NANS):c.709C>T (p.Arg237Cys) SNV Pathogenic 235191 rs878852982 GRCh37: 9:100843203-100843203
GRCh38: 9:98080921-98080921
6 NANS , TRIM14 NM_018946.4(NANS):c.398G>T (p.Gly133Val) SNV Pathogenic 235188 rs878852980 GRCh37: 9:100839249-100839249
GRCh38: 9:98076967-98076967
7 NANS , TRIM14 NM_018946.4(NANS):c.979_981dup (p.Ile327dup) Duplication Pathogenic 235189 rs878853268 GRCh37: 9:100845234-100845235
GRCh38: 9:98082952-98082953
8 NANS , TRIM14 NM_018946.4(NANS):c.448+1G>A SNV Pathogenic 235186 rs779218846 GRCh37: 9:100839300-100839300
GRCh38: 9:98077018-98077018
9 NANS , TRIM14 NM_018946.4(NANS):c.1070del (p.Ile357fs) Deletion Pathogenic 1030682 GRCh37: 9:100845327-100845327
GRCh38: 9:98083045-98083045

UniProtKB/Swiss-Prot genetic disease variations for Spondyloepimetaphyseal Dysplasia, Genevieve Type:

72
# Symbol AA change Variation ID SNP ID
1 NANS p.His29Asn VAR_076571 rs127726356
2 NANS p.Gly133Val VAR_076572 rs878852980
3 NANS p.Arg151His VAR_076573 rs140402727
4 NANS p.Tyr188His VAR_076574 rs878852981
5 NANS p.Pro189Leu VAR_076575 rs102402572
6 NANS p.Arg237Cys VAR_076576 rs878852982

Expression for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Search GEO for disease gene expression data for Spondyloepimetaphyseal Dysplasia, Genevieve Type.

Pathways for Spondyloepimetaphyseal Dysplasia, Genevieve Type

GO Terms for Spondyloepimetaphyseal Dysplasia, Genevieve Type

Sources for Spondyloepimetaphyseal Dysplasia, Genevieve Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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