Stüve-Wiedemann syndrome 1

Summary

Stüve-Wiedemann syndrome 1 (MONDO:0800043) is a disease caused by LIFR (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: LIFR (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 191
• Phenotypes (HPO): 44

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		56	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Prevalence at birth	1-5 / 10 000	20	United Arab Emirates	Validated

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0000478	Abnormality of the eye	Very frequent (80-99%)
HP:0000504	Abnormality of vision	Very frequent (80-99%)
HP:0000935	Thickened cortex of long bones	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0000966	Hypohidrosis	Very frequent (80-99%)
HP:0000975	Hyperhidrosis	Very frequent (80-99%)
HP:0001954	Recurrent fever	Very frequent (80-99%)
HP:0002652	Skeletal dysplasia	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0003016	Metaphyseal widening	Very frequent (80-99%)
HP:0003103	Abnormal cortical bone morphology	Very frequent (80-99%)
HP:0003401	Paresthesia	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0006487	Bowing of the long bones	Very frequent (80-99%)
HP:0008872	Feeding difficulties in infancy	Very frequent (80-99%)
HP:0012332	Abnormal autonomic nervous system physiology	Very frequent (80-99%)
HP:0100490	Camptodactyly of finger	Very frequent (80-99%)
HP:0000211	Trismus	Frequent (30-79%)
HP:0000632	Lacrimation abnormality	Frequent (30-79%)
HP:0000938	Osteopenia	Frequent (30-79%)
HP:0000939	Osteoporosis	Frequent (30-79%)
HP:0001371	Flexion contracture	Frequent (30-79%)
HP:0001376	Limitation of joint mobility	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001562	Oligohydramnios	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)
HP:0002099	Asthma	Frequent (30-79%)
HP:0002104	Apnea	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002757	Recurrent fractures	Frequent (30-79%)
HP:0002857	Genu valgum	Frequent (30-79%)
HP:0002987	Elbow flexion contracture	Frequent (30-79%)
HP:0006380	Knee flexion contracture	Frequent (30-79%)
HP:0007328	Impaired pain sensation	Frequent (30-79%)
HP:0010298	Smooth tongue	Frequent (30-79%)
HP:0012785	Flexion contracture of finger	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0000960	Sacral dimple	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0006844	Absent patellar reflexes	Occasional (5-29%)
HP:0008000	Decreased corneal reflex	Occasional (5-29%)
HP:0100028	Ectopic thyroid	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Stüve-Wiedemann syndrome 1
Mondo ID	MONDO:0800043
MeSH	C537502
OMIM	601559
Orphanet	3206
SNOMED CT	254097005
UMLS	C5676888
MedGen	1803541
GARD	0005045
Is cancer (heuristic)	no

Also known as: neonatal Schwartz-Jampel syndrome · neonatal Schwartz-Jampel syndrome type 2 · Schwartz-Jampel syndrome neonatal · Schwartz-Jampel syndrome type 2 · Schwartz-Jampel syndrome, neonatal · SJS2 · STUVE-Wiedemann syndrome · Stuve-Wiedemann syndrome · Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome · STWS · Stws · Stüve-Wiedemann dysplasia · Stüve-Wiedemann syndrome · Stüve-Wiedemann/Schwartz-Jampel type 2 syndrome · SWS

Data availability: 191 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Schwartz-Jampel syndrome › Stüve-Wiedemann syndrome 1

Related subtypes (1): Schwartz-Jampel syndrome 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

191 retrieved; paginated sample, class counts are floors:

116 uncertain significance, 21 likely pathogenic, 17 conflicting classifications of pathogenicity, 12 pathogenic/likely pathogenic, 11 benign/likely benign, 8 pathogenic, 4 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070966	NM_001127671.2(LIFR):c.1469C>G (p.Ser490Ter)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071419	NM_001127671.2(LIFR):c.1252C>T (p.Arg418Ter)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1372780	NM_001127671.2(LIFR):c.325G>T (p.Glu109Ter)	LIFR	Pathogenic	criteria provided, multiple submitters, no conflicts
1457803	NM_001127671.2(LIFR):c.1429_1430insT (p.Gln477fs)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1694459	NM_001127671.2(LIFR):c.2497+1G>A	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189235	NM_001127671.2(LIFR):c.2074C>T (p.Arg692Ter)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2437222	NM_001127671.2(LIFR):c.2472_2476del (p.Ser824fs)	LIFR	Pathogenic	criteria provided, multiple submitters, no conflicts
2444108	NM_001127671.2(LIFR):c.703_704del (p.Trp235fs)	LIFR	Pathogenic	criteria provided, single submitter
2690057	NM_001127671.2(LIFR):c.2034del (p.Ser679fs)	LIFR	Pathogenic	criteria provided, single submitter
2734722	NM_001127671.2(LIFR):c.1621dup (p.Thr541fs)	LIFR	Pathogenic	criteria provided, multiple submitters, no conflicts
2734723	NM_001127671.2(LIFR):c.1231_1234del (p.Asn411fs)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280316	NM_001127671.2(LIFR):c.254del (p.Asn85fs)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
281444	NM_001127671.2(LIFR):c.653dup (p.Glu219fs)	LIFR	Pathogenic	criteria provided, multiple submitters, no conflicts
2908023	NM_001127671.2(LIFR):c.396_397+2del	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
353624	NM_001127671.2(LIFR):c.1756G>T (p.Glu586Ter)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
561052	NM_001127671.2(LIFR):c.503C>G (p.Ser168Ter)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
656451	NM_001127671.2(LIFR):c.478_479del (p.Arg160fs)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
871488	NM_001127671.2(LIFR):c.756dup (p.Lys253Ter)	LIFR	Pathogenic	criteria provided, multiple submitters, no conflicts
936674	NM_001127671.2(LIFR):c.23del (p.Cys7_Leu8insTer)	LIFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
944487	NM_001127671.2(LIFR):c.2434C>T (p.Arg812Ter)	LIFR	Pathogenic	criteria provided, multiple submitters, no conflicts
1324664	NM_001127671.2(LIFR):c.210del (p.Ser71fs)	LIFR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343414	NM_001127671.2(LIFR):c.1105dup (p.Tyr369fs)	LIFR	Likely pathogenic	no assertion criteria provided
191327	NM_001127671.2(LIFR):c.1121+1G>A	LIFR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2094495	NM_001127671.2(LIFR):c.1291+2T>C	LIFR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203641	NM_001127671.2(LIFR):c.1865C>T (p.Ala622Val)	LIFR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2506373	NM_001127671.2(LIFR):c.1136_1137del (p.Tyr379fs)	LIFR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3592614	NM_001127671.2(LIFR):c.2591+2T>C	LIFR	Likely pathogenic	criteria provided, single submitter
3592619	NM_001127671.2(LIFR):c.2231G>A (p.Trp744Ter)	LIFR	Likely pathogenic	criteria provided, single submitter
3592621	NM_001127671.2(LIFR):c.2161G>T (p.Glu721Ter)	LIFR	Likely pathogenic	criteria provided, single submitter
3592625	NM_001127671.2(LIFR):c.2022G>A (p.Trp674Ter)	LIFR	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
LIFR	Definitive	Autosomal recessive	Stüve-Wiedemann syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LIFR	Orphanet:3206	Stüve-Wiedemann 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
LIFR	HGNC:6597	ENSG00000113594	P42702	Leukemia inhibitory factor receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LIFR	Leukemia inhibitory factor receptor	Signal-transducing molecule.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LIFR	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, Ig-like_fold

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
globus pallidus	1
lateral globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LIFR	269	ubiquitous	marker	medial globus pallidus, globus pallidus, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LIFR	2,136

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LIFR	P42702	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
RUNX1 regulates transcription of genes involved in interleukin signaling	1	2284.0×	0.004	LIFR
Interleukin-6 family signaling	1	1427.5×	0.004	LIFR
IL-6-type cytokine receptor ligand interactions	1	634.4×	0.005	LIFR
Transcriptional regulation by RUNX1	1	146.4×	0.017	LIFR
Signaling by Interleukins	1	64.2×	0.031	LIFR
Cytokine Signaling in Immune system	1	40.8×	0.041	LIFR
RNA Polymerase II Transcription	1	22.5×	0.063	LIFR
Gene expression (Transcription)	1	17.8×	0.070	LIFR
Generic Transcription Pathway	1	15.1×	0.074	LIFR
Immune System	1	13.0×	0.077	LIFR

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
oncostatin-M-mediated signaling pathway	1	4213.0×	7e-04	LIFR
leukemia inhibitory factor signaling pathway	1	4213.0×	7e-04	LIFR
ciliary neurotrophic factor-mediated signaling pathway	1	3370.4×	7e-04	LIFR
response to cytokine	1	374.5×	0.005	LIFR
cytokine-mediated signaling pathway	1	130.6×	0.011	LIFR
cell surface receptor signaling pathway	1	64.1×	0.018	LIFR
positive regulation of cell population proliferation	1	33.6×	0.030	LIFR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LIFR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LIFR	6	Binding:6

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	LIFR
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)
LIFR	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.