Cutis marmorata telangiectatica congenita

Summary

Cutis marmorata telangiectatica congenita (MONDO:0009055) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 32

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		300	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0000951	Abnormality of the skin	Very frequent (80-99%)
HP:0000965	Cutis marmorata	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001933	Subcutaneous hemorrhage	Very frequent (80-99%)
HP:0002814	Abnormality of the lower limb	Very frequent (80-99%)
HP:0002817	Abnormality of the upper limb	Very frequent (80-99%)
HP:0006385	Short lower limbs	Very frequent (80-99%)
HP:0100026	Arteriovenous malformation	Very frequent (80-99%)
HP:0200041	Skin erosion	Very frequent (80-99%)
HP:0000541	Retinal detachment	Frequent (30-79%)
HP:0000555	Leukocoria	Frequent (30-79%)
HP:0008065	Aplasia/Hypoplasia of the skin	Frequent (30-79%)
HP:0100585	Telangiectasia of the skin	Frequent (30-79%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0000979	Purpura	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001541	Ascites	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0004349	Reduced bone mineral density	Occasional (5-29%)
HP:0005306	Capillary hemangioma	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0007565	Multiple cafe-au-lait spots	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)
HP:0100545	Arterial stenosis	Occasional (5-29%)
HP:0100555	Asymmetric growth	Occasional (5-29%)
HP:0100627	Displacement of the urethral meatus	Occasional (5-29%)
HP:0100814	Blue nevus	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	cutis marmorata telangiectatica congenita
Mondo ID	MONDO:0009055
MeSH	C536226
OMIM	219250
Orphanet	1556
ICD-11	1359154853
SNOMED CT	254778000
UMLS	C0345419
MedGen	83381
GARD	0006228
Is cancer (heuristic)	no

Also known as: CMTC · cutis marmorata telangiectatica congenita · cutis marmorata telangiectatica congenita (disease) · hereditary cutis marmorata telangiectatica congenita · Van Lohuizen syndrome

Data availability: 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › capillary malformation › cutis marmorata telangiectatica congenita

Related subtypes (5): stork bite, familial multiple nevi flammei, capillary malformation-arteriovenous malformation syndrome, hereditary hemorrhagic telangiectasia, angioma serpiginosum

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: 1 · 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
ARL6IP6	Limited	Autosomal recessive	cutis marmorata telangiectatica congenita

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARL6IP6	Orphanet:1556	Cutis marmorata telangiectatica congenita

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
ARL6IP6	HGNC:24048	ENSG00000177917	Q8N6S5	ADP-ribosylation factor-like protein 6-interacting protein 6	gencc

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)
ARL6IP6	Other/Unknown	no		ARL6IP6

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
ganglionic eminence	1
germinal epithelium of ovary	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARL6IP6	253	ubiquitous	marker	ventricular zone, ganglionic eminence, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARL6IP6	562

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARL6IP6	Q8N6S5	56.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
ARL6IP6	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	ARL6IP6

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)
ARL6IP6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.