Craniodiaphyseal dysplasia

Summary

Craniodiaphyseal dysplasia (MONDO:0009031) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include fenfluramine hydrochloride.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 13
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000256	Macrocephaly	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000772	Abnormal rib morphology	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0002007	Frontal bossing	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0004493	Craniofacial hyperostosis	Very frequent (80-99%)
HP:0005019	Diaphyseal thickening	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0000402	Stenosis of the external auditory canal	Frequent (30-79%)
HP:0000405	Conductive hearing impairment	Frequent (30-79%)
HP:0000648	Optic atrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	craniodiaphyseal dysplasia
Mondo ID	MONDO:0009031
MeSH	C562940
OMIM	218300
Orphanet	1513
DOID	DOID:0080032
ICD-11	505073582
NCIT	C131429
SNOMED CT	205506004
UMLS	C0410539
MedGen	96080
GARD	0001567
Is cancer (heuristic)	no

Also known as: CDD · craniodiaphyseal dysplasia · Lionitis

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone remodeling disease › hyperostosis › craniodiaphyseal dysplasia

Related subtypes (8): exostosis, bone Paget disease, diffuse idiopathic skeletal hyperostosis, Caffey disease, autosomal dominant osteosclerosis, Worth type, hyperostosis corticalis generalisata, X-linked calvarial hyperostosis, sclerosteosis

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: 8 · Orphanet: 3 · 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
SOST	Supportive	Autosomal dominant	craniodiaphyseal dysplasia	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOST	Orphanet:1513	Craniodiaphyseal dysplasia
SOST	Orphanet:3152	Sclerosteosis
SOST	Orphanet:3416	Hyperostosis corticalis generalisata

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
SOST	HGNC:13771	ENSG00000167941	Q9BQB4	Sclerostin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOST	Sclerostin	Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.

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)
SOST	Other/Unknown	no		Cys_knot_C, Sclerostin/SOSTDC1, Cystine-knot_cytokine

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
descending thoracic aorta	1
male germ line stem cell (sensu Vertebrata) in testis	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOST	73	broad	marker	trabecular bone tissue, descending thoracic aorta, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOST	2,417

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOST	Q9BQB4	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	713.8×	0.006	SOST
TCF dependent signaling in response to WNT	1	117.7×	0.012	SOST
Signaling by WNT	1	112.0×	0.012	SOST
Signal Transduction	1	10.2×	0.098	SOST

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
cellular response to parathyroid hormone stimulus	1	1404.3×	0.006	SOST
negative regulation of ossification	1	624.1×	0.006	SOST
negative regulation of protein-containing complex assembly	1	455.5×	0.006	SOST
negative regulation of Wnt signaling pathway	1	343.9×	0.006	SOST
response to mechanical stimulus	1	300.9×	0.006	SOST
negative regulation of BMP signaling pathway	1	290.6×	0.006	SOST
ossification	1	227.7×	0.007	SOST
BMP signaling pathway	1	200.6×	0.007	SOST
canonical Wnt signaling pathway	1	153.2×	0.008	SOST
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.009	SOST
positive regulation of DNA-templated transcription	1	27.9×	0.036	SOST

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SOST	CIANIDANOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SOST	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CIANIDANOL	4	SOST
COUMARIN	4	SOST

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SOST	9	Binding:9

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
CIANIDANOL	4	SOST
COUMARIN	4	SOST

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SOST
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	0

Undrugged target profiles

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

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
NCT03861871	PHASE2	COMPLETED	Fenfluramine in CDKL5 Deficiency Disorder (CDD)
NCT05558371	Not specified	RECRUITING	International CDKL5 Clinical Research Network

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FENFLURAMINE HYDROCHLORIDE	4	1