Cystic hygroma

Summary

Cystic hygroma (MONDO:0009761) is a disease with 2 cohort genes and 2 clinical trials. Top therapeutic interventions include alpelisib and mirdametinib.

At a glance

• Cohort genes: 2
• ClinVar variants: 4
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cystic hygroma
Mondo ID	MONDO:0009761
EFO	EFO:1000888
MeSH	D018191
OMIM	257350
Orphanet	79486
DOID	DOID:3081
NCIT	C3724
SNOMED CT	399882002
UMLS	C0206620
MedGen	60195
GARD	0006234
MedDRA	10058949
Is cancer (heuristic)	no

Also known as: cystic hygroma · cystic hygroma, foetal · cystic lymphangioma · hygroma · macrocystic lymphatic malformation

Data availability: 4 ClinVar variants · 2 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › benign neoplasm › cardiovascular organ benign neoplasm › lymphangioma › cystic hygroma

Related subtypes (11): colonic lymphangioma, capillary lymphangioma, lymphangioendothelioma, Gorham-Stout disease, lymphedema-posterior choanal atresia syndrome, diffuse lymphatic malformation, mixed cystic lymphatic malformation, multifocal lymphangioendotheliomatosis-thrombocytopenia syndrome, macrocystic lymphatic malformation, microcystic lymphatic malformation, skin lymphangioma

Subtypes (1): abdominal cystic lymphangioma

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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
267930	46;XX;t(6;17)(q13;q21)dn		Likely pathogenic	criteria provided, single submitter
497724	NM_080680.3(COL11A2):c.966dup (p.Thr323fs)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
978633	NM_080680.3(COL11A2):c.1773+8T>A	COL11A2	Uncertain significance	criteria provided, single submitter
1705938	GRCh37/hg19 15q11.2(chr15:22770421-23082328)x1	CYFIP1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
CYFIP1	HGNC:13759	ENSG00000273749	Q7L576	Cytoplasmic FMR1-interacting protein 1	clinvar
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYFIP1	Cytoplasmic FMR1-interacting protein 1	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression.
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.

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)
CYFIP1	Other/Unknown	no		Cytoplasmic_FMR1-int, CYRIA/CYRIB_Rac1-bd
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
epithelium of esophagus	1
esophagus squamous epithelium	1
germinal epithelium of ovary	1
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYFIP1	295	ubiquitous	marker	esophagus squamous epithelium, germinal epithelium of ovary, epithelium of esophagus
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYFIP1	2,156
COL11A2	1,583

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYFIP1	Q7L576	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A2	P13942	50.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
MET activates PTK2 signaling	1	190.3×	0.019	COL11A2
RHO GTPases Activate WASPs and WAVEs	1	158.6×	0.019	CYFIP1
Collagen chain trimerization	1	129.8×	0.019	COL11A2
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.019	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.019	COL11A2
FCGR3A-mediated phagocytosis	1	93.6×	0.019	CYFIP1
Regulation of actin dynamics for phagocytic cup formation	1	92.1×	0.019	CYFIP1
Collagen degradation	1	87.8×	0.019	COL11A2
Collagen biosynthesis and modifying enzymes	1	85.2×	0.019	COL11A2
Non-integrin membrane-ECM interactions	1	77.2×	0.019	COL11A2
RHOG GTPase cycle	1	74.2×	0.019	CYFIP1
VEGFA-VEGFR2 Pathway	1	69.6×	0.019	CYFIP1
RAC2 GTPase cycle	1	63.4×	0.019	CYFIP1
RAC3 GTPase cycle	1	59.5×	0.019	CYFIP1
RAC1 GTPase cycle	1	30.5×	0.035	CYFIP1
Neutrophil degranulation	1	11.5×	0.085	CYFIP1

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
regulation of translation at postsynapse, modulating synaptic transmission	1	2808.7×	0.004	CYFIP1
positive regulation of neurotrophin TRK receptor signaling pathway	1	1685.2×	0.004	CYFIP1
soft palate development	1	1685.2×	0.004	COL11A2
regulation of modification of postsynaptic actin cytoskeleton	1	1203.7×	0.004	CYFIP1
positive regulation of Arp2/3 complex-mediated actin nucleation	1	1053.2×	0.004	CYFIP1
dendrite extension	1	842.6×	0.004	CYFIP1
ruffle organization	1	648.1×	0.005	CYFIP1
positive regulation of lamellipodium assembly	1	300.9×	0.008	CYFIP1
regulation of actin filament polymerization	1	290.6×	0.008	CYFIP1
Rac protein signal transduction	1	280.9×	0.008	CYFIP1
axon extension	1	247.8×	0.008	CYFIP1
lamellipodium assembly	1	221.7×	0.008	CYFIP1
cognition	1	142.8×	0.012	CYFIP1
cartilage development	1	125.8×	0.012	COL11A2
roof of mouth development	1	123.9×	0.012	COL11A2
collagen fibril organization	1	112.3×	0.012	COL11A2
regulation of translation	1	109.4×	0.012	CYFIP1
cell morphogenesis	1	78.8×	0.015	CYFIP1
skeletal system development	1	62.9×	0.018	COL11A2
regulation of cell shape	1	61.5×	0.018	CYFIP1
sensory perception of sound	1	50.5×	0.021	COL11A2
axon guidance	1	45.3×	0.022	CYFIP1

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
CYFIP1	0	0
COL11A2	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
CYFIP1	7	Binding:7

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	CYFIP1, COL11A2

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)
CYFIP1	7	—
COL11A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05983159	PHASE2	RECRUITING	A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
NCT07246928	Not specified	COMPLETED	Ultraspound-guided Intralesional Injection of Cystic Hygroma - A Case Report

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALPELISIB	4	1
MIRDAMETINIB	2	1