Ehlers-Danlos syndrome, spondylodysplastic type

Summary

Ehlers-Danlos syndrome, spondylodysplastic type (MONDO:0007526) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 320
• Phenotypes (HPO): 37

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		34	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000230	Gingivitis	Very frequent (80-99%)
HP:0000256	Macrocephaly	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000963	Thin skin	Very frequent (80-99%)
HP:0000973	Cutis laxa	Very frequent (80-99%)
HP:0000974	Hyperextensible skin	Very frequent (80-99%)
HP:0001166	Arachnodactyly	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001371	Flexion contracture	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0001642	Pulmonic stenosis	Very frequent (80-99%)
HP:0001650	Aortic valve stenosis	Very frequent (80-99%)
HP:0001763	Pes planus	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005328	Progeroid facial appearance	Very frequent (80-99%)
HP:0007469	Palmoplantar cutis gyrata	Very frequent (80-99%)
HP:0009125	Lipodystrophy	Very frequent (80-99%)
HP:0010511	Long toe	Very frequent (80-99%)
HP:0100813	Testicular torsion	Very frequent (80-99%)
HP:0000160	Narrow mouth	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000506	Telecanthus	Frequent (30-79%)
HP:0000653	Sparse eyelashes	Frequent (30-79%)
HP:0000938	Osteopenia	Frequent (30-79%)
HP:0000987	Atypical scarring of skin	Frequent (30-79%)
HP:0001000	Abnormality of skin pigmentation	Frequent (30-79%)
HP:0001075	Atrophic scars	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002209	Sparse scalp hair	Frequent (30-79%)
HP:0002652	Skeletal dysplasia	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)
HP:0045075	Sparse eyebrow	Frequent (30-79%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0002751	Kyphoscoliosis	Occasional (5-29%)
HP:0006481	Abnormality of primary teeth	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, spondylodysplastic type
Mondo ID	MONDO:0007526
MeSH	C536201
Orphanet	75496
DOID	DOID:0050802
SNOMED CT	720861000
GARD	0009991
Is cancer (heuristic)	no

Also known as: B4GALT7-CDG · defective biosynthesis of proteodermatan sulfate · defective biosynthesis of proteodermatan sulphate · dermatan sulfate proteoglycan · dermatan sulphate proteoglycan · EDS, progeroid type · EDSSPD1 · Ehlers-Danlos syndrome with short stature and limb anomalies · Ehlers-Danlos syndrome, progeroid type (former) · Ehlers-Danlos syndrome, spondylodysplastic type, 1 · galactosyltransferase 1 deficiency · galactosyltransferase I deficiency · PDS · Pds, defective biosynthesis of · proteodermatan sulfate, defective biosynthesis of · spondylodysplastic Ehlers-Danlos syndrome · XGPT deficiency · xylosylprotein 4-beta-galactosyltransferase deficiency

Data availability: 320 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › Ehlers-Danlos syndrome, spondylodysplastic type

Related subtypes (56): Neu-Laxova syndrome, inborn mitochondrial metabolism disorder, MGAT2-congenital disorder of glycosylation, ALDH18A1-related de Barsy syndrome, classic homocystinuria, Larsen-like syndrome, B3GAT3 type, Nijmegen breakage syndrome, Peters plus syndrome, Wiedemann-Rautenstrauch syndrome, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, SHORT syndrome, mucosulfatidosis, CHIME syndrome, creatine transporter deficiency, multiple congenital anomalies-hypotonia-seizures syndrome 2, SLC35A2-congenital disorder of glycosylation, SSR4-congenital disorder of glycosylation, Fabry disease, occipital horn syndrome, Ehlers-Danlos syndrome, musculocontractural type, temtamy preaxial brachydactyly syndrome, B4GALT1-congenital disorder of glycosylation, AICA-ribosiduria, COG7-congenital disorder of glycosylation, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, Al-Gazali syndrome, COG1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, Nijmegen breakage syndrome-like disorder, multiple congenital anomalies-hypotonia-seizures syndrome 1, multiple congenital anomalies-hypotonia-seizures syndrome 3, autism spectrum disorder - epilepsy - arthrogryposis syndrome, cutis laxa, autosomal dominant 3, SLC39A8-CDG, transketolase deficiency, mucopolysaccharidosis-plus syndrome, Cockayne syndrome, pontocerebellar hypoplasia type 1, mandibuloacral dysplasia, hyperphosphatasia-intellectual disability syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, CADDS, XYLT1-congenital disorder of glycosylation, hypophosphatasia, sterol biosynthesis disorder, mucolipidosis, mucopolysaccharidosis, oligosaccharidosis, encephalopathy due to sulfite oxidase deficiency, Fanconi anemia, autosomal recessive cutis laxa type 2, Zellweger spectrum disorders, pseudohypoparathyroidism, developmental and epileptic encephalopathy, 77, glycosylphosphatidylinositol biosynthesis defect 15, progressive hypotonia-intellectual disability-facial dysmorphism syndrome due to FYVE-defective RBSN

Subtypes (3): Ehlers-Danlos syndrome, spondylocheirodysplastic type, Ehlers-Danlos syndrome, spondylodysplastic type, 2, Ehlers-Danlos syndrome, spondylodysplastic type, 1

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

320 retrieved; paginated sample, class counts are floors:

157 likely benign, 109 uncertain significance, 16 conflicting classifications of pathogenicity, 16 pathogenic, 9 benign, 5 benign/likely benign, 5 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1354563	NM_007255.3(B4GALT7):c.225C>A (p.Cys75Ter)	B4GALT7	Pathogenic	criteria provided, single submitter
1406837	NM_007255.3(B4GALT7):c.325del (p.Leu109fs)	B4GALT7	Pathogenic	criteria provided, single submitter
2165476	NM_007255.3(B4GALT7):c.242_243del (p.Pro81fs)	B4GALT7	Pathogenic	criteria provided, multiple submitters, no conflicts
225691	NM_007255.3(B4GALT7):c.122T>C (p.Leu41Pro)	B4GALT7	Pathogenic	no assertion criteria provided
253108	NM_007255.3(B4GALT7):c.421C>T (p.Arg141Trp)	B4GALT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253109	NM_007255.3(B4GALT7):c.277dup (p.His93fs)	B4GALT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
423889	NM_007255.3(B4GALT7):c.268del (p.Trp90fs)	B4GALT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4759179	NM_007255.3(B4GALT7):c.579_580del (p.Tyr194fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4759187	NM_007255.3(B4GALT7):c.474_475del (p.Ile159fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4759191	NM_007255.3(B4GALT7):c.118_119del (p.Ser40fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4759192	NM_007255.3(B4GALT7):c.39G>A (p.Trp13Ter)	B4GALT7	Pathogenic	criteria provided, single submitter
4769041	NM_007255.3(B4GALT7):c.230dup (p.Glu78fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4771301	NM_007255.3(B4GALT7):c.397C>T (p.Gln133Ter)	B4GALT7	Pathogenic	criteria provided, single submitter
4773076	NM_007255.3(B4GALT7):c.276_277dup (p.His93fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4799475	NM_007255.3(B4GALT7):c.99_100insGA (p.Leu34fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4808196	NM_007255.3(B4GALT7):c.678_679del (p.Glu227fs)	B4GALT7	Pathogenic	criteria provided, single submitter
4810085	NM_007255.3(B4GALT7):c.448dup (p.Leu150fs)	B4GALT7	Pathogenic	criteria provided, single submitter
5612	NM_007255.3(B4GALT7):c.617T>C (p.Leu206Pro)	B4GALT7	Pathogenic	no assertion criteria provided
5613	NM_007255.3(B4GALT7):c.808C>T (p.Arg270Cys)	B4GALT7	Pathogenic	criteria provided, multiple submitters, no conflicts
2064958	NM_007255.3(B4GALT7):c.414-2A>G	B4GALT7	Likely pathogenic	criteria provided, single submitter
2129648	NM_007255.3(B4GALT7):c.179_413+354del	B4GALT7	Likely pathogenic	criteria provided, single submitter
2179225	NM_007255.3(B4GALT7):c.50+1G>A	B4GALT7	Likely pathogenic	criteria provided, single submitter
4771556	NM_007255.3(B4GALT7):c.639+1G>A	B4GALT7	Likely pathogenic	criteria provided, single submitter
5611	NM_007255.3(B4GALT7):c.557C>A (p.Ala186Asp)	B4GALT7	Likely pathogenic	criteria provided, single submitter
1096969	NM_007255.3(B4GALT7):c.517C>T (p.Leu173=)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1186652	NM_007255.3(B4GALT7):c.767G>A (p.Arg256His)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1519959	NM_007255.3(B4GALT7):c.128T>G (p.Phe43Cys)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197288	NM_007255.3(B4GALT7):c.687C>T (p.Asp229=)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2139658	NM_007255.3(B4GALT7):c.762_763del (p.Phe255fs)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
253110	NM_007255.3(B4GALT7):c.641G>A (p.Cys214Tyr)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
B4GALT7	Definitive	Autosomal recessive	Ehlers-Danlos syndrome, spondylodysplastic type, 1	7

Orphanet rare-disease linkage (cohort genes)

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
B4GALT7	HGNC:930	ENSG00000027847	Q9UBV7	Beta-1,4-galactosyltransferase 7	gencc,clinvar
FAM153A	HGNC:29940	ENSG00000170074	Q9UHL3	Protein FAM153A	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: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

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
FAM153A	Other/Unknown	no		FAM153

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
tendon of biceps brachii	1
left testis	1
right testis	1
testis	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
FAM153A	131		yes	right testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
B4GALT7	1,645
FAM153A	358

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
B4GALT7	Q9UBV7	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM153A	Q9UHL3	52.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 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: 2

Druggability breadth: 0 of 2 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
FAM153A	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: 2; 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	1	FAM153A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
B4GALT7	0	—
FAM153A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.