Blepharocheilodontic syndrome

Summary

Blepharocheilodontic syndrome (MONDO:0007339) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 14
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		55	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0000492	Abnormal eyelid morphology	Very frequent (80-99%)
HP:0007651	Ectropion of lower eyelids	Very frequent (80-99%)
HP:0009743	Distichiasis	Very frequent (80-99%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000405	Conductive hearing impairment	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0000504	Abnormality of vision	Frequent (30-79%)
HP:0000670	Carious teeth	Frequent (30-79%)
HP:0000698	Conical tooth	Frequent (30-79%)
HP:0006101	Finger syndactyly	Frequent (30-79%)
HP:0012905	Euryblepharon	Frequent (30-79%)
HP:0002023	Anal atresia	Occasional (5-29%)
HP:0011362	Abnormal hair quantity	Occasional (5-29%)
HP:0200040	Epidermoid cyst	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	blepharocheilodontic syndrome
Mondo ID	MONDO:0007339
MeSH	C536188
OMIM	119580
Orphanet	1997
DOID	DOID:0080344
ICD-11	755252042
SNOMED CT	717911008
UMLS	C1861536
MedGen	349302
GARD	0002071
Is cancer (heuristic)	no

Also known as: BCD syndrome · BCDS · BCDS1 · blepharo-cheilo-dontic syndrome · blepharo-cheilo-odontic syndrome · blepharocheilodontic syndrome · clefting, ectropion, and conical teeth · clefting-ectropion-conical teeth syndrome · ectropion inferior cleft lip and or palate · ectropion inferior-cleft lip and or palate syndrome · ectropion inferior-cleft lip and/or palate syndrome · Elsching syndrome · Elschnig syndrome · lagophthalmia with bilateral cleft lip and palate · lagophthalmia-cleft lip and palate syndrome

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › blepharocheilodontic syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (3): Martinez Monasterio Pinheiro syndrome, blepharocheilodontic syndrome 2, blepharocheilodontic syndrome 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 6 · 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
CDH1	Definitive	Autosomal dominant	blepharocheilodontic syndrome 1	15
CTNND1	Definitive	Autosomal dominant	blepharocheilodontic syndrome 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH1	Orphanet:1331	Familial prostate cancer
CDH1	Orphanet:199306	Cleft lip/palate
CDH1	Orphanet:1997	Blepharo-cheilo-odontic syndrome
CDH1	Orphanet:227535	Hereditary breast cancer
CDH1	Orphanet:26106	Hereditary diffuse gastric cancer
CTNND1	Orphanet:1997	Blepharo-cheilo-odontic syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	gencc
CTNND1	HGNC:2515	ENSG00000198561	O60716	Catenin delta-1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
CTNND1	Catenin delta-1	Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
CTNND1	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
esophagus squamous epithelium	1
gingival epithelium	1
jejunal mucosa	1
esophagus mucosa	1
lower esophagus mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium
CTNND1	134	ubiquitous	marker	ventricular zone, esophagus mucosa, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH1	8,738
CTNND1	2,883

Intra-cohort edges

A	B	Sources
CDH1	CTNND1	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDH1	P12830	22
CTNND1	O60716	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
InlA-mediated entry of Listeria monocytogenes into host cells	2	1268.9×	2e-05	CDH1, CTNND1
Regulation of CDH1 Function	2	951.7×	2e-05	CDH1, CTNND1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	2	496.5×	6e-05	CDH1, CTNND1
Adherens junctions interactions	2	248.3×	2e-04	CDH1, CTNND1
Degradation of CDH1	2	196.9×	2e-04	CDH1, CTNND1
Activation of STAT3 by cadherin engagement	2	163.1×	3e-04	CDH1, CTNND1
CDH11 homotypic and heterotypic interactions	1	815.7×	0.007	CTNND1
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	713.8×	0.007	CDH1
Regulation of CDH19 Expression and Function	1	713.8×	0.007	CTNND1
Apoptotic cleavage of cell adhesion proteins	1	519.1×	0.007	CDH1
Listeria monocytogenes entry into host cells	1	519.1×	0.007	CDH1
Regulation of CDH11 function	1	519.1×	0.007	CTNND1
Regulation of CDH1 mRNA translation by microRNAs	1	519.1×	0.007	CDH1
Positive Regulation of CDH1 Gene Transcription	1	475.8×	0.007	CDH1
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	439.2×	0.007	CDH1
Developmental Lineage of Mammary Stem Cells	1	380.7×	0.008	CDH1
Formation of definitive endoderm	1	356.9×	0.008	CDH1
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	271.9×	0.010	CDH1
Apoptotic cleavage of cellular proteins	1	237.9×	0.010	CDH1
Apoptotic execution phase	1	237.9×	0.010	CDH1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	228.4×	0.010	CDH1
VEGFR2 mediated vascular permeability	1	203.9×	0.011	CTNND1
RHO GTPases activate IQGAPs	1	173.0×	0.011	CDH1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	167.9×	0.011	CDH1
Bacterial Infection Pathways	1	167.9×	0.011	CDH1
Gastrulation	1	129.8×	0.014	CDH1
Cell-cell junction organization	1	124.1×	0.014	CDH1
Cell junction organization	1	93.6×	0.018	CDH1
MITF-M-dependent gene expression	1	90.6×	0.018	CDH1
Transcriptional and post-translational regulation of MITF-M expression and activity	1	89.2×	0.018	CDH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell-cell adhesion mediated by cadherin	2	411.0×	2e-04	CDH1, CTNND1
negative regulation of blood vessel branching	1	8426.0×	0.001	CTNND1
cell-cell adhesion	2	101.5×	0.001	CDH1, CTNND1
response to heparin	1	2808.7×	0.003	CDH1
positive regulation of protein localization to cell-cell junction	1	2808.7×	0.003	CTNND1
regulation of protein catabolic process at postsynapse, modulating synaptic transmission	1	2106.5×	0.003	CDH1
negative regulation of D-glucose transmembrane transport	1	1685.2×	0.003	CTNND1
cellular response to indole-3-methanol	1	1685.2×	0.003	CDH1
response to Gram-positive bacterium	1	1404.3×	0.003	CDH1
desmosome assembly	1	1203.7×	0.003	CDH1
negative regulation of intracellular signal transduction	1	1053.2×	0.003	CTNND1
positive regulation of protein localization	1	702.2×	0.004	CDH1
cellular response to lithium ion	1	561.7×	0.005	CDH1
negative regulation of cell-cell adhesion	1	495.6×	0.005	CDH1
negative regulation of axon extension	1	366.4×	0.007	CDH1
cell migration involved in sprouting angiogenesis	1	324.1×	0.007	CTNND1
pituitary gland development	1	324.1×	0.007	CDH1
adherens junction organization	1	255.3×	0.007	CDH1
regulation of postsynaptic membrane neurotransmitter receptor levels	1	247.8×	0.007	CTNND1
calcium-dependent cell-cell adhesion	1	240.7×	0.007	CDH1
cell-cell junction assembly	1	221.7×	0.008	CDH1
positive regulation of protein import into nucleus	1	210.7×	0.008	CDH1
synapse assembly	1	115.4×	0.014	CDH1
response to toxic substance	1	105.3×	0.014	CDH1
cell morphogenesis	1	78.8×	0.018	CDH1
homophilic cell-cell adhesion	1	70.2×	0.020	CDH1
neuron projection development	1	61.1×	0.022	CDH1
negative regulation of cell migration	1	55.8×	0.023	CDH1
protein localization to plasma membrane	1	54.4×	0.023	CDH1
Wnt signaling pathway	1	49.9×	0.024	CTNND1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
CDH1	0	0
CTNND1	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
CDH1	18	Binding:18
CTNND1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	CDH1, CTNND1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CDH1	18	—
CTNND1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07133464	Not specified	RECRUITING	CDH1-associated Blepharocheilodontic Syndrome Registry