Heart defect - tongue hamartoma - polysyndactyly syndrome

Summary

Heart defect - tongue hamartoma - polysyndactyly syndrome (MONDO:0009008) is a disease caused by WDPCP (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: WDPCP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 172
• Phenotypes (HPO): 6

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)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0001643	Patent ductus arteriosus	Very frequent (80-99%)
HP:0001682	Subvalvular aortic stenosis	Very frequent (80-99%)
HP:0011802	Hamartoma of tongue	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0001233	2-3 finger syndactyly	Frequent (30-79%)
HP:0100835	Benign neoplasm of the central nervous system	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	heart defect - tongue hamartoma - polysyndactyly syndrome
Mondo ID	MONDO:0009008
MeSH	C535849
OMIM	217085
Orphanet	1338
DOID	DOID:0111591
UMLS	C1857587
MedGen	341804
GARD	0004166
Is cancer (heuristic)	no

Also known as: CHDTHP · congenital heart defects, hamartomas of tongue, and polysyndactyly · heart defect - tongue hamartoma - polysyndactyly syndrome · heart defect, tongue hamartoma and polysyndactyly · Orstavik Lindemann Solberg syndrome · Ostravik-Lindemann-Solberg syndrome

Data availability: 172 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome without intellectual disability › heart defect - tongue hamartoma - polysyndactyly syndrome

Related subtypes (167): Treacher-Collins syndrome, branchio-oto-renal syndrome, acrorenal syndrome, Townes-Brocks syndrome, Ascher syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, branchiooculofacial syndrome, Gordon syndrome, cataract-aberrant oral frenula-growth delay syndrome, cherubism, Alagille syndrome, cleft palate-lateral synechia syndrome, blepharocheilodontic syndrome, craniofacial-deafness-hand syndrome, cryptomicrotia-brachydactyly-excess fingertip arch syndrome, Beare-Stevenson cutis gyrata syndrome, Cyprus facial-neuromusculoskeletal syndrome, deafness-craniofacial syndrome, short stature-valvular heart disease-characteristic facies syndrome, 3-M syndrome, external auditory canal atresia-vertical talus-hypertelorism syndrome, femoral-facial syndrome, multinodular goiter-cystic kidney-polydactyly syndrome, hand-foot-genital syndrome, Bencze syndrome, oculoauriculovertebral spectrum with radial defects, Holt-Oram syndrome, mullerian duct anomalies-limb anomalies syndrome, Aase-Smith syndrome, LADD syndrome, Noonan syndrome with multiple lentigines, median nodule of the upper lip, Nager acrofacial dysostosis, Marshall syndrome, Binder syndrome, Schilbach-Rott syndrome, nasopalpebral lipoma-coloboma syndrome, autosomal dominant prognathism, short stature-craniofacial anomalies-genital hypoplasia syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, scalp-ear-nipple syndrome, flat face-microstomia-ear anomaly syndrome, Czeizel-Losonci syndrome, otospondylomegaepiphyseal dysplasia, autosomal dominant, ventricular extrasystoles with syncopal episodes-perodactyly-robin sequence syndrome, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, acrofacial dysostosis, Weyers type, Freeman-Sheldon syndrome, Ackerman syndrome, acro-renal-mandibular syndrome, acrocraniofacial dysostosis, PAGOD syndrome, alar cartilages hypoplasia-coloboma-telecanthus syndrome, microcephaly-albinism-digital anomalies syndrome, fetal akinesia deformation sequence, Cooper-Jabs syndrome, Barber-Say syndrome, Beemer-Ertbruggen syndrome, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, camptodactyly syndrome, Guadalajara type 1, camptodactyly syndrome, Guadalajara type 2, heart defects-limb shortening syndrome, Verloove Vanhorick-Brubakk syndrome, Juberg-Hayward syndrome, Fraser syndrome, split hand-foot malformation 1 with sensorineural hearing loss, von Voss-Cherstvoy syndrome, autosomal recessive faciodigitogenital syndrome, gingival fibromatosis-facial dysmorphism syndrome, Fibulo-ulnar hypoplasia-renal anomalies syndrome, frontofacionasal dysplasia, genito-palato-cardiac syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Holzgreve-Wagner-Rehder syndrome, hydrocephaly-tall stature-joint laxity syndrome, McKusick-Kaufman syndrome, acrofrontofacionasal dysostosis 2, Vici syndrome, Donohue syndrome, Dahlberg-Borer-Newcomer syndrome, macrosomia-microphthalmia-cleft palate syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, Nijmegen breakage syndrome, lethal congenital contracture syndrome 1, Richieri Costa-da Silva syndrome, Keipert syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, ichthyosis-oral and digital anomalies syndrome, otoonychoperoneal syndrome, PHAVER syndrome, polysyndactyly-cardiac malformation syndrome, postaxial acrofacial dysostosis, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, renal-genital-middle ear anomalies, Richieri Costa-Pereira syndrome, SHORT syndrome, tetraamelia-multiple malformations syndrome, thymic-renal-anal-lung dysplasia, trigonocephaly-bifid nose-acral anomalies syndrome, white forelock with malformations, syndactyly-telecanthus-anogenital and renal malformations syndrome, Abruzzo-Erickson syndrome, CHILD syndrome, pentalogy of Cantrell, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, short tarsus-absence of lower eyelashes syndrome, PARC syndrome, CODAS syndrome, pectus excavatum-macrocephaly-dysplastic nails syndrome, velo-facial-skeletal syndrome, anophthalmia plus syndrome, van den Ende-Gupta syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, diaphragmatic defect-limb deficiency-skull defect syndrome, cleft lip/palate-intestinal malrotation-cardiopathy syndrome, Matthew-Wood syndrome, microcephaly-cardiac defect-lung malsegmentation syndrome, dislocation of the hip-dysmorphism syndrome, short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome, grange syndrome, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, arhinia, choanal atresia, and microphthalmia, anonychia-microcephaly syndrome, developmental malformations-deafness-dystonia syndrome, lethal congenital contracture syndrome 2, craniolenticulosutural dysplasia, 8q22.1 microdeletion syndrome, Braddock syndrome, choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome, BNAR syndrome, Frias syndrome, lethal congenital contracture syndrome 3, Fontaine progeroid syndrome, microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type, Nijmegen breakage syndrome-like disorder, Warsaw breakage syndrome, even-plus syndrome, split-foot malformation-mesoaxial polydactyly syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, digitotalar dysmorphism, heart-hand syndrome type 2, night blindness-skeletal anomalies-dysmorphism syndrome, Charlie M syndrome, facial dysmorphism-anorexia-cachexia-eye and skin anomalies syndrome, cleft lip-retinopathy syndrome, Cole-Carpenter syndrome, progressive non-infectious anterior vertebral fusion, dysmorphism-pectus carinatum-joint laxity syndrome, Hirschsprung disease-type D brachydactyly syndrome, mandibuloacral dysplasia, contractures - webbed neck - micrognathia - hypoplastic nipples syndrome, Thomas syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, branchiootic syndrome, auricular abnormalities-cleft lip with or without cleft palate-ocular abnormalities syndrome, Axenfeld-Rieger syndrome, macrostomia-preauricular tags-external ophthalmoplegia syndrome, pelvis syndrome, Fanconi anemia, van der Woude syndrome, hypertrichosis-acromegaloid facial appearance syndrome, 49,XYYYY syndrome, congenital vertebral-cardiac-renal anomalies syndrome, structural heart defects and renal anomalies syndrome, Greig cephalopolysyndactyly-contiguous gene syndrome

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

172 retrieved; paginated sample, class counts are floors:

112 uncertain significance, 20 conflicting classifications of pathogenicity, 20 likely benign, 11 likely pathogenic, 4 pathogenic/likely pathogenic, 3 pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076112	NM_015910.7(WDPCP):c.547A>T (p.Lys183Ter)	WDPCP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172573	GRCh37/hg19 2p15(chr2:63521229-63572056)x1	WDPCP	Pathogenic	criteria provided, single submitter
1179146	NM_015910.7(WDPCP):c.1809_1812+6del	WDPCP	Pathogenic	criteria provided, single submitter
1451557	NM_015910.7(WDPCP):c.755G>A (p.Trp252Ter)	WDPCP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162668	NM_015910.7(WDPCP):c.552_553del (p.Cys185fs)	WDPCP	Pathogenic	criteria provided, multiple submitters, no conflicts
2882889	NM_015910.7(WDPCP):c.512_515del (p.Asp171fs)	WDPCP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
690307	NM_015910.7(WDPCP):c.526_527del (p.Leu176fs)	WDPCP	Pathogenic/Likely pathogenic	no assertion criteria provided
1327998	NM_015910.7(WDPCP):c.541C>T (p.Gln181Ter)	WDPCP	Likely pathogenic	criteria provided, single submitter
2584976	NM_015910.7(WDPCP):c.2101G>T (p.Glu701Ter)	WDPCP	Likely pathogenic	criteria provided, single submitter
3062312	NM_015910.7(WDPCP):c.2050_2053del (p.Gln684fs)	WDPCP	Likely pathogenic	criteria provided, single submitter
3586811	NM_015910.7(WDPCP):c.1600C>T (p.Gln534Ter)	WDPCP	Likely pathogenic	criteria provided, single submitter
3586817	NM_015910.7(WDPCP):c.1436-1G>A	WDPCP	Likely pathogenic	criteria provided, single submitter
3586825	NM_015910.7(WDPCP):c.917dup (p.Ser307fs)	WDPCP	Likely pathogenic	criteria provided, single submitter
3586844	NM_015910.7(WDPCP):c.3G>A (p.Met1Ile)	WDPCP	Likely pathogenic	criteria provided, single submitter
3767117	NM_015910.7(WDPCP):c.256C>T (p.Arg86Ter)	WDPCP	Likely pathogenic	criteria provided, single submitter
3780795	NM_015910.7(WDPCP):c.881_884del (p.Lys294fs)	WDPCP	Likely pathogenic	criteria provided, single submitter
631865	NM_015910.7(WDPCP):c.209-1G>A	WDPCP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
969340	NM_015910.7(WDPCP):c.633+2T>C	WDPCP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1005664	NM_015910.7(WDPCP):c.691A>G (p.Ile231Val)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1058192	NM_015910.7(WDPCP):c.771T>A (p.Ser257=)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1339333	NM_015910.7(WDPCP):c.1492T>G (p.Cys498Gly)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1446584	NM_015910.7(WDPCP):c.1435+18A>G	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162669	NM_015910.7(WDPCP):c.160G>A (p.Asp54Asn)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193387	NM_015910.7(WDPCP):c.13T>C (p.Phe5Leu)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2052283	NM_015910.7(WDPCP):c.500-17_500-13del	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220911	NM_015910.7(WDPCP):c.176T>A (p.Ile59Asn)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2240187	NM_015910.7(WDPCP):c.2068T>C (p.Ser690Pro)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
336767	NM_015910.7(WDPCP):c.1079C>T (p.Ser360Leu)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522195	NM_015910.7(WDPCP):c.1448G>A (p.Arg483Gln)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
531833	NM_015910.7(WDPCP):c.159G>A (p.Ala53=)	WDPCP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
WDPCP	Strong	Autosomal recessive	heart defect - tongue hamartoma - polysyndactyly syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDPCP	Orphanet:110	Bardet-Biedl syndrome
WDPCP	Orphanet:1338	Heart defect-tongue hamartoma-polysyndactyly 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
WDPCP	HGNC:28027	ENSG00000143951	O95876	WD repeat-containing and planar cell polarity effector protein fritz homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDPCP	WD repeat-containing and planar cell polarity effector protein fritz homolog	Probable effector of the planar cell polarity signaling pathway which regulates the septin cytoskeleton in both ciliogenesis and collective cell movements.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDPCP	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Frtz, WD40_repeat_dom_sf

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
kidney epithelium	1
mucosa of paranasal sinus	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDPCP	253	ubiquitous	marker	pancreatic ductal cell, kidney epithelium, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDPCP	787

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDPCP	O95876	1

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
regulation of embryonic cell shape	1	8426.0×	0.001	WDPCP
auditory receptor cell morphogenesis	1	4213.0×	0.001	WDPCP
septin cytoskeleton organization	1	4213.0×	0.001	WDPCP
tongue morphogenesis	1	3370.4×	0.001	WDPCP
digestive system development	1	3370.4×	0.001	WDPCP
respiratory system development	1	3370.4×	0.001	WDPCP
podocyte cell migration	1	2407.4×	0.002	WDPCP
regulation of ruffle assembly	1	2106.5×	0.002	WDPCP
circulatory system development	1	1404.3×	0.002	WDPCP
regulation of fibroblast migration	1	1296.3×	0.002	WDPCP
establishment of planar polarity	1	1053.2×	0.002	WDPCP
regulation of establishment of cell polarity	1	936.2×	0.002	WDPCP
cilium organization	1	601.9×	0.003	WDPCP
regulation of focal adhesion assembly	1	601.9×	0.003	WDPCP
regulation of cilium assembly	1	601.9×	0.003	WDPCP
intraciliary transport	1	561.7×	0.003	WDPCP
neural tube development	1	526.6×	0.003	WDPCP
establishment of protein localization	1	432.1×	0.003	WDPCP
camera-type eye development	1	358.6×	0.004	WDPCP
embryonic digit morphogenesis	1	300.9×	0.004	WDPCP
roof of mouth development	1	247.8×	0.005	WDPCP
regulation of protein localization	1	205.5×	0.006	WDPCP
smoothened signaling pathway	1	181.2×	0.006	WDPCP
kidney development	1	140.4×	0.008	WDPCP
cilium assembly	1	73.6×	0.014	WDPCP
nervous system development	1	45.9×	0.022	WDPCP

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
WDPCP	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	WDPCP

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)
WDPCP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.