Pelviscapular dysplasia

Summary

Pelviscapular dysplasia (MONDO:0009845) is a disease caused by TBX15 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TBX15 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 21
• Phenotypes (HPO): 24

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000256	Macrocephaly	Obligate (100%)
HP:0000470	Short neck	Obligate (100%)
HP:0000882	Hypoplastic scapulae	Obligate (100%)
HP:0000946	Hypoplastic ilia	Obligate (100%)
HP:0001156	Brachydactyly	Obligate (100%)
HP:0001374	Congenital hip dislocation	Obligate (100%)
HP:0002987	Elbow flexion contracture	Obligate (100%)
HP:0003041	Humeroradial synostosis	Obligate (100%)
HP:0003097	Short femur	Obligate (100%)
HP:0003943	Abnormality of the joint spaces of the elbow	Obligate (100%)
HP:0004987	Mesomelic leg shortening	Obligate (100%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0002693	Abnormality of the skull base	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000377	Abnormal pinna morphology	Frequent (30-79%)
HP:0000402	Stenosis of the external auditory canal	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000490	Deeply set eye	Frequent (30-79%)
HP:0000581	Blepharophimosis	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002162	Low posterior hairline	Frequent (30-79%)
HP:0005989	Redundant neck skin	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pelviscapular dysplasia
Mondo ID	MONDO:0009845
MeSH	C535550
OMIM	260660
Orphanet	93333
SNOMED CT	719299009
UMLS	C1850040
MedGen	342400
GARD	0001555
Is cancer (heuristic)	no

Also known as: Cousin syndrome · craniofacial dysmorphism, hypoplasia of scapula and pelvis and short stature · familial pelvis-scapular dysplasia · pelviscapular dysplasia

Data availability: 21 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › dysostosis › pelviscapular dysplasia

Related subtypes (107): trigonocephaly, spondylocostal dysostosis, synostosis, Adams-Oliver syndrome, adactylia, unilateral, ADULT syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, Cooks syndrome, brachydactyly-arterial hypertension syndrome, fibular aplasia-ectrodactyly syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, congenital pseudoarthrosis of clavicle, external auditory canal atresia-vertical talus-hypertelorism syndrome, femoral-facial syndrome, hand-foot-genital syndrome, oculoauriculovertebral spectrum with radial defects, IVIC syndrome, nail-patella syndrome, patella aplasia/hypoplasia, pelvis-shoulder dysplasia, phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome, postaxial tetramelic oligodactyly, Currarino triad, radio-renal syndrome, splenogonadal fusion-limb defects-micrognathia syndrome, Karsch-Neugebauer syndrome, tetramelic monodactyly, tibia, hypoplasia or aplasia of, with polydactyly, humerus trochlea aplasia, Aphalangy-hemivertebrae-urogenital-intestinal dysgenesis syndrome, camptodactyly syndrome, Guadalajara type 2, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, split hand-foot malformation 1 with sensorineural hearing loss, EEM syndrome, lethal faciocardiomelic dysplasia, femur-fibula-ulna complex, Gollop-Wolfgang complex, acromesomelic dysplasia 2B, Fuhrmann syndrome, absence deformity of leg-cataract syndrome, intellectual disability-spasticity-ectrodactyly syndrome, fibular aplasia, tibial campomelia, and oligosyndactyly syndrome, otoonychoperoneal syndrome, rapadilino syndrome, EEC syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, tetraamelia-multiple malformations syndrome, thrombocytopenia-absent radius syndrome, phocomelia, Schinzel type, ulna hypoplasia-intellectual disability syndrome, absent radius-anogenital anomalies syndrome, ulnar hypoplasia-split foot syndrome, aphalangy-syndactyly-microcephaly syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, autosomal recessive amelia, pelvic dysplasia-arthrogryposis of lower limbs syndrome, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, genitopatellar syndrome, Duane-radial ray syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, camptodactyly syndrome, Guadalajara type 3, mammary-digital-nail syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, split-foot malformation-mesoaxial polydactyly syndrome, amniotic band syndrome, radial deficiency-tibial hypoplasia syndrome, mandibulofacial dysostosis, oromandibular-limb anomalies syndrome, congenital pseudoarthrosis of the limbs, oculomaxillofacial dysostosis, shoulder and thorax deformity-congenital heart disease syndrome, femoral agenesis/hypoplasia, progressive non-infectious anterior vertebral fusion, hemimelia, heart-hand syndrome, split hand-foot malformation, Melhem-Fahl syndrome, limb transversal defect-cardiac anomaly syndrome, frontonasal dysplasia, imperforate oropharynx-costo vetebral anomalies syndrome, non-syndromic amelia, congenital absence of upper arm and forearm with hand present, congenital absence of thigh and lower leg with foot present, congenital absence of both forearm and hand, congenital absence of both lower leg and foot, acheiria, apodia, split hand, split foot, hyperphalangy, Prata-Liberal-Goncalves syndrome, syngnathia multiple anomalies, hereditary thrombocytosis with transverse limb defect, thalidomide embryopathy, tibial aplasia-ectrodactyly syndrome, bipartite talus, acrofacial dysostosis, adactyly of foot, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, Rubinstein-Taybi syndrome, ischio-vertebral syndrome, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, preaxial digit brachydactyly-webbed fingers, proximal femoral focal deficiency, dysostosis multiplex, Ain-Naz type

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

21 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 6 benign, 2 benign/likely benign, 2 pathogenic, 1 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
5822	NM_001330677.2(TBX15):c.1348del (p.Ile450fs)	TBX15	Pathogenic	no assertion criteria provided
5823	NM_001330677.2(TBX15):c.1350del (p.Pro451fs)	TBX15	Pathogenic	no assertion criteria provided
289694	NM_001330677.2(TBX15):c.1325G>A (p.Arg442Lys)	TBX15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029193	NM_001330677.2(TBX15):c.943A>G (p.Ile315Val)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1376334	NM_001330677.2(TBX15):c.1404G>C (p.Gln468His)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1408298	NM_001330677.2(TBX15):c.1208C>T (p.Ala403Val)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1408532	NM_001330677.2(TBX15):c.1721A>G (p.Asn574Ser)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1433420	NM_001330677.2(TBX15):c.752T>C (p.Phe251Ser)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1434092	NM_001330677.2(TBX15):c.1150G>A (p.Val384Met)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1905650	NM_001330677.2(TBX15):c.493A>G (p.Ile165Val)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
2056128	NM_001330677.2(TBX15):c.1609G>A (p.Ala537Thr)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
500123	NM_001330677.2(TBX15):c.979C>T (p.Arg327Cys)	TBX15	Uncertain significance	criteria provided, multiple submitters, no conflicts
1221451	NM_001330677.2(TBX15):c.1710C>T (p.Ser570=)	TBX15	Benign	criteria provided, multiple submitters, no conflicts
1240908	NM_001330677.2(TBX15):c.466C>A (p.His156Asn)	TBX15	Benign	criteria provided, multiple submitters, no conflicts
1263403	NM_001330677.2(TBX15):c.694-49T>C	TBX15	Benign	criteria provided, multiple submitters, no conflicts
1600982	NM_001330677.2(TBX15):c.861+14C>G	TBX15	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
287637	NM_001330677.2(TBX15):c.980G>A (p.Arg327His)	TBX15	Likely benign	criteria provided, multiple submitters, no conflicts
593097	NM_001330677.2(TBX15):c.837A>G (p.Thr279=)	TBX15	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
594474	NM_001330677.2(TBX15):c.1697T>G (p.Met566Arg)	TBX15	Benign	criteria provided, multiple submitters, no conflicts
767693	NM_001330677.2(TBX15):c.1477C>G (p.Pro493Ala)	TBX15	Benign	criteria provided, multiple submitters, no conflicts
783944	NM_001330677.2(TBX15):c.519C>T (p.Tyr173=)	TBX15	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
TBX15	Definitive	Autosomal recessive	pelviscapular dysplasia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBX15	Orphanet:93333	Pelviscapular dysplasia

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
TBX15	HGNC:11594	ENSG00000092607	Q96SF7	T-box transcription factor TBX15	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBX15	T-box transcription factor TBX15	Probable transcriptional regulator involved in the development of the skeleton of the limb, vertebral column and head.

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)
TBX15	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS

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
gastrocnemius	1
muscle of leg	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBX15	172	broad	marker	gastrocnemius, muscle of leg, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBX15	1,204

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBX15	Q96SF7	61.41

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
embryonic cranial skeleton morphogenesis	1	581.1×	0.004	TBX15
cell fate specification	1	526.6×	0.004	TBX15
positive regulation of DNA-templated transcription	1	27.9×	0.048	TBX15
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TBX15

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
TBX15	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	TBX15

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)
TBX15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.