neonatal Marfan syndrome

Summary

neonatal Marfan syndrome (MONDO:0017309) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 8
• Phenotypes (HPO): 43

Clinical features

Signs & symptoms

Clinical features (HPO)

43 HPO clinical features (Orphanet curated; top 43 by frequency):

HPO ID	Term	Frequency
HP:0001653	Mitral regurgitation	Obligate (100%)
HP:0002097	Emphysema	Obligate (100%)
HP:0005180	Tricuspid regurgitation	Obligate (100%)
HP:0000268	Dolichocephaly	Very frequent (80-99%)
HP:0000485	Megalocornea	Very frequent (80-99%)
HP:0000768	Pectus carinatum	Very frequent (80-99%)
HP:0000973	Cutis laxa	Very frequent (80-99%)
HP:0001083	Ectopia lentis	Very frequent (80-99%)
HP:0001166	Arachnodactyly	Very frequent (80-99%)
HP:0001181	Adducted thumb	Very frequent (80-99%)
HP:0001270	Motor delay	Very frequent (80-99%)
HP:0001371	Flexion contracture	Very frequent (80-99%)
HP:0001518	Small for gestational age	Very frequent (80-99%)
HP:0001626	Abnormality of the cardiovascular system	Very frequent (80-99%)
HP:0001634	Mitral valve prolapse	Very frequent (80-99%)
HP:0001704	Tricuspid valve prolapse	Very frequent (80-99%)
HP:0001713	Abnormal cardiac ventricle morphology	Very frequent (80-99%)
HP:0002643	Neonatal respiratory distress	Very frequent (80-99%)
HP:0004970	Ascending tubular aorta aneurysm	Very frequent (80-99%)
HP:0008124	Talipes calcaneovarus	Very frequent (80-99%)
HP:0008734	Decreased testicular size	Very frequent (80-99%)
HP:0010511	Long toe	Very frequent (80-99%)
HP:0011003	High myopia	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)
HP:0012418	Hypoxemia	Very frequent (80-99%)
HP:0030148	Heart murmur	Very frequent (80-99%)
HP:0100578	Lipoatrophy	Very frequent (80-99%)
HP:0100625	Enlarged thorax	Very frequent (80-99%)
HP:0100693	Iridodonesis	Very frequent (80-99%)
HP:0100807	Long fingers	Very frequent (80-99%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000490	Deeply set eye	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000592	Blue sclerae	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001265	Hyporeflexia	Frequent (30-79%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0002616	Aortic root aneurysm	Frequent (30-79%)
HP:0002705	High, narrow palate	Frequent (30-79%)
HP:0009901	Crumpled ear	Frequent (30-79%)
HP:0012771	Increased arm span	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	neonatal Marfan syndrome
Mondo ID	MONDO:0017309
Orphanet	284979
ICD-11	1102890898
SNOMED CT	763839005
UMLS	C4016054
MedGen	864491
GARD	0021128
Is cancer (heuristic)	no

Also known as: neonatal MFS

Data availability: 8 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › neonatal Marfan syndrome

Related subtypes (59): arterial disorder, ischemic colitis, thrombotic disease, capillary disorder, angiodysplasia, hepatic vascular disorder, vascular hemostatic disease, vein disorder, ischemic disease, peripheral vascular disease, venous thromboembolism, ocular vascular disorder, cholesterol embolism, thoracic outlet syndrome, idiopathic spontaneous coronary artery dissection, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, angioosteohypertrophic syndrome, Bannayan-Riley-Ruvalcaba syndrome, arterial tortuosity syndrome, hereditary arterial and articular multiple calcification syndrome, pulmonary venoocclusive disease, multiple cutaneous and mucosal venous malformations, arterial dissection-lentiginosis syndrome, patent ductus arteriosus, multisystemic smooth muscle dysfunction syndrome, STING-associated vasculopathy with onset in infancy, capillary malformation, Ehlers-Danlos syndrome, vascular-like type, calciphylaxis, Ehlers-Danlos syndrome, vascular type, lethal arteriopathy syndrome due to fibulin-4 deficiency, congenital portosystemic shunt, arterial calcification of infancy, vasculitis, Loeys-Dietz syndrome, skin vascular disease, lymphatic malformation, familial thoracic aortic aneurysm and aortic dissection, congenital anomaly of superior vena cava, congenital anomaly of the inferior vena cava, congenital anomaly of hepatic vein, congenital renal artery stenosis, internal carotid agenesis, coronary sinus stenosis, coronary sinus atresia, vascular occlusion disorder, vascular insufficiency disorder, blood vessel neoplasm, vascular ectasia, vascular disorder of penis, fibrocartilaginous embolism, vascular malformation, lymphatic vessel neoplasm, neurovascular disorder, superior vena cava syndrome, coronary microvascular disorder, segmental arterial mediolysis, bleeding disorder, vascular-type, arterial tortuosity-bone fragility 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

8 retrieved; paginated sample, class counts are floors:

7 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
16438	NM_000138.5(FBN1):c.3220T>C (p.Cys1074Arg)	FBN1	Pathogenic	no assertion criteria provided
16441	NM_000138.5(FBN1):c.3965-2A>T	FBN1	Pathogenic	no assertion criteria provided
16442	NM_000138.5(FBN1):c.4087+1G>A	FBN1	Pathogenic	criteria provided, single submitter
16447	NM_000138.5(FBN1):c.3391A>T (p.Asn1131Tyr)	FBN1	Pathogenic	no assertion criteria provided
16457	NM_000138.5(FBN1):c.3217G>A (p.Glu1073Lys)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
16462	NM_000138.5(FBN1):c.3095G>A (p.Cys1032Tyr)	FBN1	Pathogenic	criteria provided, single submitter
16465	NM_000138.5(FBN1):c.3257G>A (p.Cys1086Tyr)	FBN1	Pathogenic	no assertion criteria provided
16446	NM_000138.5(FBN1):c.3128A>G (p.Lys1043Arg)	FBN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 24 · Orphanet: 11 · 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
FBN1	Definitive	Autosomal dominant	Marfan syndrome	24

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia

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
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.

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)
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

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
decidua	1
skin of hip	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBN1	3,640

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBN1	P35555	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Elastic fibre formation	1	335.9×	0.008	FBN1
TGF-beta receptor signaling activates SMADs	1	326.3×	0.008	FBN1
Molecules associated with elastic fibres	1	308.6×	0.008	FBN1
Integrin cell surface interactions	1	134.3×	0.012	FBN1
Degradation of the extracellular matrix	1	117.7×	0.012	FBN1
Post-translational protein phosphorylation	1	100.2×	0.012	FBN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	FBN1

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
post-embryonic eye morphogenesis	1	5617.3×	0.001	FBN1
obsolete sequestering of BMP in extracellular matrix	1	4213.0×	0.001	FBN1
obsolete sequestering of TGFbeta in extracellular matrix	1	4213.0×	0.001	FBN1
negative regulation of osteoclast development	1	3370.4×	0.001	FBN1
embryonic eye morphogenesis	1	1532.0×	0.002	FBN1
cellular response to insulin-like growth factor stimulus	1	1296.3×	0.002	FBN1
cell adhesion mediated by integrin	1	674.1×	0.004	FBN1
negative regulation of osteoclast differentiation	1	543.6×	0.004	FBN1
metanephros development	1	510.7×	0.004	FBN1
camera-type eye development	1	358.6×	0.004	FBN1
lung alveolus development	1	351.1×	0.004	FBN1
cellular response to transforming growth factor beta stimulus	1	276.3×	0.005	FBN1
glucose metabolic process	1	255.3×	0.005	FBN1
glucose homeostasis	1	130.6×	0.009	FBN1
skeletal system development	1	125.8×	0.009	FBN1
gene expression	1	79.9×	0.013	FBN1
heart development	1	78.8×	0.013	FBN1

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
FBN1	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	FBN1

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)
FBN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.