spondylodysplastic Ehlers-Danlos syndrome

Summary

spondylodysplastic Ehlers-Danlos syndrome (MONDO:0034021) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 6
• Phenotypes (HPO): 105

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		24	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

105 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0002751	Kyphoscoliosis	Very frequent (80-99%)
HP:0002761	Generalized joint laxity	Very frequent (80-99%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000325	Triangular face	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0000592	Blue sclerae	Frequent (30-79%)
HP:0000926	Platyspondyly	Frequent (30-79%)
HP:0000938	Osteopenia	Frequent (30-79%)
HP:0000946	Hypoplastic ilia	Frequent (30-79%)
HP:0000963	Thin skin	Frequent (30-79%)
HP:0000974	Hyperextensible skin	Frequent (30-79%)
HP:0000977	Soft skin	Frequent (30-79%)
HP:0001027	Soft, doughy skin	Frequent (30-79%)
HP:0001167	Abnormality of finger	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001371	Flexion contracture	Frequent (30-79%)
HP:0001373	Joint dislocation	Frequent (30-79%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0001385	Hip dysplasia	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0001763	Pes planus	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002659	Increased susceptibility to fractures	Frequent (30-79%)
HP:0002828	Multiple joint contractures	Frequent (30-79%)
HP:0003468	Abnormal vertebral morphology	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004993	Slender long bones with narrow diaphyses	Frequent (30-79%)
HP:0008453	Congenital kyphoscoliosis	Frequent (30-79%)
HP:0012368	Flat face	Frequent (30-79%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000337	Broad forehead	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000894	Short clavicles	Occasional (5-29%)
HP:0000954	Single transverse palmar crease	Occasional (5-29%)
HP:0000973	Cutis laxa	Occasional (5-29%)
HP:0001075	Atrophic scars	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0001654	Abnormal heart valve morphology	Occasional (5-29%)
HP:0001772	Talipes equinovalgus	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spondylodysplastic Ehlers-Danlos syndrome
Mondo ID	MONDO:0034021
Orphanet	536471
UMLS	C5680154
MedGen	1814455
GARD	0022214
Is cancer (heuristic)	no

Also known as: spondylodysplastic EDS

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Ehlers-Danlos syndrome › spondylodysplastic Ehlers-Danlos syndrome

Related subtypes (24): Ehlers-Danlos syndrome, classic type, Ehlers-Danlos syndrome, hypermobility type, Ehlers-Danlos syndrome, arthrochalasia type, Ehlers-Danlos syndrome, spondylodysplastic type, Ehlers-Danlos syndrome, periodontitis type, Ehlers-Danlos syndrome, autosomal dominant, type unspecified, joint laxity, familial, Ehlers-Danlos syndrome, fibronectinemic type, Ehlers-Danlos syndrome, dermatosparaxis type, brittle cornea syndrome, X-linked Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, musculocontractural type, Ehlers-Danlos syndrome due to tenascin-X deficiency, Ehlers-Danlos syndrome, Beasley-Cohen type, Ehlers-Danlos syndrome, kyphoscoliotic type, 2, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Ehlers-Danlos syndrome, vascular-like type, Ehlers-Danlos/osteogenesis imperfecta syndrome, Ehlers-Danlos syndrome, vascular type, Bethlem myopathy 2, Ehlers-Danlos syndrome, classic-like, 2, COL1A1-related Ehlers-Danlos syndrome, COL1A2-related Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, classic-like, 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2165476	NM_007255.3(B4GALT7):c.242_243del (p.Pro81fs)	B4GALT7	Pathogenic	criteria provided, multiple submitters, no conflicts
4847121	NM_007255.3(B4GALT7):c.90del (p.Val31fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4847371	NC_000005.9:g.(?177027132)(177027262_177031179)del	B4GALT7	Pathogenic	criteria provided, single submitter
5613	NM_007255.3(B4GALT7):c.808C>T (p.Arg270Cys)	B4GALT7	Pathogenic	criteria provided, multiple submitters, no conflicts
5611	NM_007255.3(B4GALT7):c.557C>A (p.Ala186Asp)	B4GALT7	Likely pathogenic	criteria provided, single submitter
1438619	NM_007255.3(B4GALT7):c.737C>T (p.Ser246Leu)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
B4GALT7	Orphanet:75496	B4GALT7-related spondylodysplastic Ehlers-Danlos syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
B4GALT7	HGNC:930	ENSG00000027847	Q9UBV7	Beta-1,4-galactosyltransferase 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
B4GALT7	Beta-1,4-galactosyltransferase 7	Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
B4GALT7	Enzyme (other)	yes	2.4.1.133	Galactosyl_T, Galactosyl_T_C, Galactosyl_T_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
B4GALT7	259	ubiquitous	marker	tendon of biceps brachii, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
B4GALT7	1,645

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
B4GALT7	Q9UBV7	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chondroitin sulfate/dermatan sulfate metabolism	1	951.7×	0.005	B4GALT7
Diseases associated with glycosaminoglycan metabolism	1	761.3×	0.005	B4GALT7
Defective B4GALT7 causes EDS, progeroid type	1	571.0×	0.005	B4GALT7
Heparan sulfate/heparin (HS-GAG) metabolism	1	543.8×	0.005	B4GALT7
Glycosaminoglycan-protein linkage region biosynthesis	1	393.8×	0.006	B4GALT7
Glycosaminoglycan metabolism	1	219.6×	0.008	B4GALT7
Diseases of glycosylation	1	131.3×	0.011	B4GALT7
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.011	B4GALT7
Diseases of metabolism	1	80.4×	0.015	B4GALT7
Disease	1	13.1×	0.084	B4GALT7
Metabolism	1	11.6×	0.086	B4GALT7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glycosaminoglycan-protein linkage region biosynthetic process	1	4213.0×	0.002	B4GALT7
proteoglycan metabolic process	1	1872.4×	0.002	B4GALT7
supramolecular fiber organization	1	1053.2×	0.002	B4GALT7
glycosaminoglycan biosynthetic process	1	842.6×	0.002	B4GALT7
proteoglycan biosynthetic process	1	842.6×	0.002	B4GALT7
negative regulation of fibroblast proliferation	1	495.6×	0.003	B4GALT7
protein N-linked glycosylation	1	263.3×	0.005	B4GALT7
protein modification process	1	244.2×	0.005	B4GALT7
carbohydrate metabolic process	1	135.9×	0.007	B4GALT7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
B4GALT7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
B4GALT7	2.4.1.133, 2.4.1.38	xylosylprotein 4-beta-galactosyltransferase, beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	B4GALT7
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
B4GALT7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.