phocomelia, Schinzel type

Summary

phocomelia, Schinzel type (MONDO:0010164) is a disease caused by WNT7A (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: WNT7A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12
• Phenotypes (HPO): 31

Clinical features

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0009380	Finger aplasia	Very frequent (80-99%)
HP:0001849	Foot oligodactyly	Very frequent (80-99%)
HP:0002164	Nail dysplasia	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0002990	Fibular aplasia	Very frequent (80-99%)
HP:0002992	Abnormality of tibia morphology	Very frequent (80-99%)
HP:0003498	Disproportionate short stature	Very frequent (80-99%)
HP:0003982	Absent ulna	Very frequent (80-99%)
HP:0006487	Bowing of the long bones	Very frequent (80-99%)
HP:0008517	Aplasia/Hypoplasia of the sacrum	Very frequent (80-99%)
HP:0009103	Aplasia/Hypoplasia involving the pelvis	Very frequent (80-99%)
HP:0100257	Ectrodactyly	Very frequent (80-99%)
HP:0000151	Aplasia of the uterus	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000470	Short neck	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0002984	Hypoplasia of the radius	Frequent (30-79%)
HP:0002986	Radial bowing	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000411	Protruding ear	Occasional (5-29%)
HP:0001362	Skull defect	Occasional (5-29%)
HP:0001789	Hydrops fetalis	Occasional (5-29%)
HP:0001883	Talipes	Occasional (5-29%)
HP:0002023	Anal atresia	Occasional (5-29%)
HP:0002435	Meningocele	Occasional (5-29%)
HP:0002575	Tracheoesophageal fistula	Occasional (5-29%)
HP:0002705	High, narrow palate	Occasional (5-29%)
HP:0003041	Humeroradial synostosis	Occasional (5-29%)
HP:0003196	Short nose	Occasional (5-29%)
HP:0008736	Hypoplasia of penis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	phocomelia, Schinzel type
Mondo ID	MONDO:0010164
MeSH	C535612
OMIM	276820
Orphanet	2879
DOID	DOID:0112181
ICD-11	1732271544
SNOMED CT	715522000
UMLS	C1848651
MedGen	336388
GARD	0009212
Is cancer (heuristic)	no

Also known as: AARRS · absence of ulna and fibula with severe limb deficiency · Al Awadi Teebi Farag syndrome · Al Awadi-Raas-Rothschild syndrome · Al-Awadi-Raas-Rothschild syndrome · Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome · aplasia/hypoplasia of limbs and pelvis · congenital absence of ulna and fibula · profound limb deficiency, thoracic dystrophy, unusual facies, and normal intelligence · severe limb deficit · Teebi Naguib Al Awadi syndrome · ulna and fibula absence of with severe limb deficiency

Data availability: 12 ClinVar variants · 2 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 › phocomelia, Schinzel type

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, pelviscapular dysplasia, rapadilino syndrome, EEC syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, tetraamelia-multiple malformations syndrome, thrombocytopenia-absent radius syndrome, 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

12 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
253008	NM_004625.4(WNT7A):c.304C>T (p.Arg102Trp)	LOC126806608	Pathogenic	no assertion criteria provided
1338765	NM_004625.4:c.(71+1_72-1)_(298+1_299-1)del	WNT7A	Pathogenic	no assertion criteria provided
3393509	NM_004625.4(WNT7A):c.814G>T (p.Glu272Ter)	WNT7A	Pathogenic	no assertion criteria provided
35537	NM_004625.4(WNT7A):c.610G>A (p.Gly204Ser)	WNT7A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
40130	NM_004625.4(WNT7A):c.664C>T (p.Arg222Trp)	WNT7A	Pathogenic	no assertion criteria provided
40302	NM_004625.4(WNT7A):c.214G>A (p.Glu72Lys)	WNT7A	Pathogenic	no assertion criteria provided
4526604	NM_004625.4(WNT7A):c.399C>A (p.Cys133Ter)	LOC126806608	Likely pathogenic	criteria provided, single submitter
8060	NM_004625.4(WNT7A):c.874C>T (p.Arg292Cys)	WNT7A	Likely pathogenic	criteria provided, single submitter
497790	NM_004625.4(WNT7A):c.1028C>T (p.Thr343Met)	WNT7A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3333230	NM_004625.4(WNT7A):c.889A>G (p.Thr297Ala)	WNT7A	Uncertain significance	criteria provided, multiple submitters, no conflicts
4277606	NM_004625.4(WNT7A):c.735dup (p.Asn246fs)	WNT7A	Uncertain significance	criteria provided, single submitter
1286438	NM_004625.4(WNT7A):c.298+37C>A	WNT7A	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
WNT7A	Strong	Autosomal recessive	phocomelia, Schinzel type	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT7A	Orphanet:2854	Fuhrmann syndrome
WNT7A	Orphanet:2879	Phocomelia, Schinzel type

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
WNT7A	HGNC:12786	ENSG00000154764	O00755	Protein Wnt-7a	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT7A	Protein Wnt-7a	Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WNT7A	Other/Unknown	no		Wnt, Wnt7, Wnt_CS

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
cortical plate	1
endometrium epithelium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT7A	96	broad	yes	cortical plate, endometrium epithelium, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WNT7A	1,809

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WNT7A	O00755	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
WNT ligand biogenesis and trafficking	1	423.0×	0.005	WNT7A
Class B/2 (Secretin family receptors)	1	190.3×	0.005	WNT7A

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
asymmetric protein localization involved in cell fate determination	1	16852.0×	0.002	WNT7A
postsynapse assembly	1	8426.0×	0.002	WNT7A
positive regulation of protein localization to presynapse	1	8426.0×	0.002	WNT7A
skeletal muscle satellite cell activation	1	5617.3×	0.002	WNT7A
oviduct development	1	5617.3×	0.002	WNT7A
positive regulation of excitatory synapse assembly	1	5617.3×	0.002	WNT7A
central nervous system vasculogenesis	1	3370.4×	0.002	WNT7A
regulation of axon diameter	1	3370.4×	0.002	WNT7A
skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration	1	2808.7×	0.002	WNT7A
uterus morphogenesis	1	2808.7×	0.002	WNT7A
embryonic axis specification	1	2407.4×	0.002	WNT7A
stem cell development	1	2407.4×	0.002	WNT7A
cerebellar granule cell differentiation	1	2106.5×	0.002	WNT7A
lens fiber cell development	1	2106.5×	0.002	WNT7A
positive regulation of epithelial cell proliferation involved in wound healing	1	1685.2×	0.002	WNT7A
somatic stem cell division	1	1532.0×	0.002	WNT7A
establishment of blood-brain barrier	1	1404.3×	0.002	WNT7A
cell proliferation in forebrain	1	1296.3×	0.002	WNT7A
excitatory synapse assembly	1	1296.3×	0.002	WNT7A
synaptic vesicle recycling	1	1203.7×	0.002	WNT7A
secondary palate development	1	1203.7×	0.002	WNT7A
presynapse assembly	1	1203.7×	0.002	WNT7A
wound healing, spreading of epidermal cells	1	1053.2×	0.002	WNT7A
positive regulation of protein metabolic process	1	991.3×	0.002	WNT7A
dendritic spine morphogenesis	1	887.0×	0.003	WNT7A
sex differentiation	1	842.6×	0.003	WNT7A
cartilage condensation	1	766.0×	0.003	WNT7A
neurotransmitter secretion	1	702.2×	0.003	WNT7A
negative regulation of neurogenesis	1	624.1×	0.003	WNT7A
embryonic hindlimb morphogenesis	1	581.1×	0.003	WNT7A

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
WNT7A	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	WNT7A

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)
WNT7A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.