Leri-Weill dyschondrosteosis

Summary

Leri-Weill dyschondrosteosis (MONDO:0007481) is a disease caused by SHOX (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: SHOX (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 48
• Phenotypes (HPO): 37

Clinical features

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0031095	Abnormal humerus morphology	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0001191	Abnormal carpal morphology	Very frequent (80-99%)
HP:0001387	Joint stiffness	Very frequent (80-99%)
HP:0001804	Hypoplastic fingernail	Very frequent (80-99%)
HP:0002644	Abnormality of pelvic girdle bone morphology	Very frequent (80-99%)
HP:0002818	Abnormal morphology of the radius	Very frequent (80-99%)
HP:0002823	Abnormality of femur morphology	Very frequent (80-99%)
HP:0002970	Genu varum	Very frequent (80-99%)
HP:0002982	Tibial bowing	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0002984	Hypoplasia of the radius	Very frequent (80-99%)
HP:0002986	Radial bowing	Very frequent (80-99%)
HP:0002992	Abnormality of tibia morphology	Very frequent (80-99%)
HP:0003022	Hypoplasia of the ulna	Very frequent (80-99%)
HP:0003027	Mesomelia	Very frequent (80-99%)
HP:0003031	Ulnar bowing	Very frequent (80-99%)
HP:0003067	Madelung deformity	Very frequent (80-99%)
HP:0003272	Abnormality of the hip bone	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0005019	Diaphyseal thickening	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0005736	Short tibia	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0006248	Limited wrist movement	Very frequent (80-99%)
HP:0006443	Patellar aplasia	Very frequent (80-99%)
HP:0006459	Dorsal subluxation of ulna	Very frequent (80-99%)
HP:0008873	Disproportionate short-limb short stature	Very frequent (80-99%)
HP:0010579	Cone-shaped epiphysis	Very frequent (80-99%)
HP:0010624	Aplastic/hypoplastic toenail	Very frequent (80-99%)
HP:0040071	Abnormal morphology of ulna	Very frequent (80-99%)
HP:0100777	Exostoses	Very frequent (80-99%)
HP:0002683	Abnormality of the calvaria	Frequent (30-79%)
HP:0002857	Genu valgum	Frequent (30-79%)
HP:0003042	Elbow dislocation	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Leri-Weill dyschondrosteosis
Mondo ID	MONDO:0007481
OMIM	127300
Orphanet	240
DOID	DOID:0060847
NCIT	C126560
SNOMED CT	17818006
UMLS	C0265309
MedGen	75562
GARD	0003224
NORD	1070
Is cancer (heuristic)	no

Also known as: DCo · dyschondrosteosis · Leri Weill dyschondrosteosis · Leri-Weill dyschondrosteosis · Leri-Weill dyschondrosteosis, Pseudoautosomal dominant · Leri-Weill dyschondrostosis · Leri-Weill syndrome · LWD · Léri-Weill dyschondrosteosis · Léri-Weill syndrome

Data availability: 48 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › Leri-Weill dyschondrosteosis

Related subtypes (49): atelosteogenesis, midface dysplasia, Kashin-Beck disease, achondroplasia, Boomerang dysplasia, campomelic dysplasia, cleidocranial dysplasia 1, hypochondroplasia, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, Kniest dysplasia, pseudoachondroplasia, ulna metaphyseal dysplasia syndrome, acheiropody, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, bone dysplasia, lethal Holmgren type, cleidocranial dysplasia, recessive form, diastrophic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, lethal Kniest-like dysplasia, metaphyseal chondrodysplasia, Kaitila type, metaphyseal chondrodysplasia, Spahr type, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, pycnodysostosis, pyknoachondrogenesis, Pyle disease, schneckenbecken dysplasia, mesomelia-synostoses syndrome, lethal chondrodysplasia, Seller type, acrocapitofemoral dysplasia, brachyolmia, Desbuquois dysplasia, fibrochondrogenesis, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, spondyloepimetaphyseal dysplasia, cleidocranial dysplasia 2, arterial tortuosity-bone fragility syndrome, linkeropathy

Subtypes (1): Madelung deformity

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

48 retrieved; paginated sample, class counts are floors:

20 pathogenic, 8 uncertain significance, 6 likely pathogenic, 5 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 3 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4795120	NC_000023.11:g.(790906_867686)del		Pathogenic	criteria provided, single submitter
1686186	NM_000451.4(SHOX):c.334C>T (p.Gln112Ter)	LOC107652445	Pathogenic	criteria provided, single submitter
1807413	NM_000451.4(SHOX):c.454C>T (p.Gln152Ter)	LOC107652445	Pathogenic	criteria provided, multiple submitters, no conflicts
9875	NM_000451.4(SHOX):c.394C>G (p.Leu132Val)	LOC107652445	Pathogenic	no assertion criteria provided
1256555	NM_000451.4(SHOX):c.518G>A (p.Arg173His)	SHOX	Pathogenic	criteria provided, multiple submitters, no conflicts
1686187	NM_000451.4(SHOX):c.335A>C (p.Gln112Pro)	SHOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686189	NM_000451.4(SHOX):c.463G>C (p.Gly155Arg)	SHOX	Pathogenic	criteria provided, single submitter
1686190	NM_000451.4(SHOX):c.670G>A (p.Ala224Thr)	SHOX	Pathogenic	criteria provided, single submitter
1686191	NM_000451.4(SHOX):c.673CACCCGCACCTG[1] (p.225HPHL[1])	SHOX	Pathogenic	criteria provided, single submitter
1686193	NM_000451.4(SHOX):c.805del (p.Ser269fs)	SHOX	Pathogenic	criteria provided, single submitter
29994	NM_000451.4(SHOX):c.508G>C (p.Ala170Pro)	SHOX	Pathogenic	criteria provided, single submitter
29995	NM_000451.4(SHOX):c.509C>A (p.Ala170Asp)	SHOX	Pathogenic	no assertion criteria provided
586575	NM_000451.4(SHOX):c.352_353del (p.Arg118fs)	SHOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66087	NC_000024.9:g.730550_778092del	SHOX	Pathogenic	no assertion criteria provided
933226	NM_000451.4(SHOX):c.-19G>A	SHOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9872	NM_000451.4(SHOX):c.583C>T (p.Arg195Ter)	SHOX	Pathogenic	criteria provided, multiple submitters, no conflicts
9873	NM_000451.4(SHOX):c.597C>G (p.Tyr199Ter)	SHOX	Pathogenic	no assertion criteria provided
9874	NG_009385.2:g.(?5001)(40068_?)del	SHOX	Pathogenic	no assertion criteria provided
9877	NM_000451.4(SHOX):c.181del (p.Glu61fs)	SHOX	Pathogenic	no assertion criteria provided
9878	NM_000451.4(SHOX):c.517C>T (p.Arg173Cys)	SHOX	Pathogenic	criteria provided, multiple submitters, no conflicts
9879	NM_000451.4(SHOX):c.502C>T (p.Arg168Trp)	SHOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9880	NM_000451.4(SHOX):c.728dup (p.Pro244fs)	SHOX	Pathogenic	criteria provided, single submitter
9882	NM_000451.4(SHOX):c.304G>T (p.Glu102Ter)	SHOX	Pathogenic	no assertion criteria provided
9884	NC_000023.11:g.(651585_658784)_(659412_1759412)del	SHOX	Pathogenic	no assertion criteria provided
3062248	NM_000451.4(SHOX):c.419del (p.His140fs)	LOC107652445	Likely pathogenic	criteria provided, single submitter
4688006	NM_000451.4(SHOX):c.425C>G (p.Pro142Arg)	LOC107652445	Likely pathogenic	criteria provided, single submitter
1333444	NM_000451.4(SHOX):c.250G>T (p.Glu84Ter)	SHOX	Likely pathogenic	criteria provided, single submitter
3069196	NM_000451.4(SHOX):c.675_676insA (p.Pro226fs)	SHOX	Likely pathogenic	criteria provided, single submitter
3601963	NM_000451.4(SHOX):c.379G>T (p.Glu127Ter)	SHOX	Likely pathogenic	criteria provided, single submitter
9876	NM_000451.4(SHOX):c.458G>T (p.Arg153Leu)	SHOX	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · 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
SHOX	Definitive	X-linked	Leri-Weill dyschondrosteosis	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SHOX	Orphanet:240	Léri-Weill dyschondrosteosis
SHOX	Orphanet:2632	Langer mesomelic dysplasia
SHOX	Orphanet:314795	SHOX-related short stature

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
SHOX	HGNC:10853	ENSG00000185960	O15266	Short stature homeobox protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SHOX	Short stature homeobox protein	Transcription factor that controls fundamental aspects of growth.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SHOX	Transcription factor	no		HTH_motif, HD, OAR_dom

Expression context

Cohort genes with no expression data: 0.

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
calcaneal tendon	1
subcutaneous adipose tissue	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SHOX	31	tissue_specific	yes	calcaneal tendon, subcutaneous adipose tissue, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SHOX	1,001

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SHOX	O15266	63.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
skeletal system development	1	125.8×	0.024	SHOX
positive regulation of transcription by RNA polymerase II	1	14.9×	0.086	SHOX
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SHOX

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
SHOX	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SHOX

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)
SHOX	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.