microcephalic osteodysplastic primordial dwarfism type II

Summary

microcephalic osteodysplastic primordial dwarfism type II (MONDO:0008872) is a disease caused by PCNT (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: PCNT (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 666
• Phenotypes (HPO): 52
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

52 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000448	Prominent nose	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0001611	Hypernasal speech	Very frequent (80-99%)
HP:0001620	Abnormally high-pitched voice	Very frequent (80-99%)
HP:0002213	Fine hair	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0002812	Coxa vara	Very frequent (80-99%)
HP:0002866	Hypoplastic iliac wing	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0003275	Narrow pelvis bone	Very frequent (80-99%)
HP:0003498	Disproportionate short stature	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0009804	Tooth agenesis	Very frequent (80-99%)
HP:0009906	Aplasia/Hypoplasia of the earlobes	Very frequent (80-99%)
HP:0000055	Abnormality of female external genitalia	Frequent (30-79%)
HP:0000278	Retrognathia	Frequent (30-79%)
HP:0000293	Full cheeks	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Frequent (30-79%)
HP:0000430	Underdeveloped nasal alae	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000691	Microdontia	Frequent (30-79%)
HP:0000958	Dry skin	Frequent (30-79%)
HP:0001053	Hypopigmented skin patches	Frequent (30-79%)
HP:0001956	Truncal obesity	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0007565	Multiple cafe-au-lait spots	Frequent (30-79%)
HP:0100840	Aplasia/Hypoplasia of the eyebrow	Frequent (30-79%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000826	Precocious puberty	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001601	Laryngomalacia	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002205	Recurrent respiratory infections	Occasional (5-29%)
HP:0002617	Dilatation	Occasional (5-29%)
HP:0002777	Tracheal stenosis	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0045025	Narrow palpebral fissure	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephalic osteodysplastic primordial dwarfism type II
Mondo ID	MONDO:0008872
MeSH	C565898
OMIM	210720
Orphanet	2637
DOID	DOID:0060609
SNOMED CT	254103003
UMLS	C0432246
MedGen	96587
GARD	0009844
Is cancer (heuristic)	no

Also known as: Majewski osteodysplastic primordial dwarfism type II · microcephalic osteodysplastic primordial dwarfism type 2 · microcephalic osteodysplastic primordial dwarfism with tooth abnormalities · microcephalic osteodysplastic primordial dwarfism, type II · MOPD II · MOPD type II · MOPD2 · osteodysplastic primordial dwarfism type 2

Data availability: 666 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › microcephaly › microcephalic osteodysplastic primordial dwarfism › microcephalic osteodysplastic primordial dwarfism type II

Related subtypes (2): microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism, type 3

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

600 retrieved; paginated sample, class counts are floors:

200 uncertain significance, 146 conflicting classifications of pathogenicity, 68 benign, 54 likely pathogenic, 50 pathogenic, 43 benign/likely benign, 21 likely benign, 18 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069878	NM_006031.6(PCNT):c.6412dup (p.Val2138fs)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127247	NM_006031.6(PCNT):c.196G>T (p.Gly66Ter)	PCNT	Pathogenic	no assertion criteria provided
1323422	NM_006031.6(PCNT):c.3465-1G>C	PCNT	Pathogenic	criteria provided, single submitter
1323423	NM_006031.6(PCNT):c.4655C>A (p.Ser1552Ter)	PCNT	Pathogenic	criteria provided, single submitter
1323425	NM_006031.6(PCNT):c.9700+1G>A	PCNT	Pathogenic	criteria provided, single submitter
1323427	NM_006031.6(PCNT):c.7511del (p.Lys2504fs)	PCNT	Pathogenic	criteria provided, single submitter
1332726	NM_006031.6(PCNT):c.1444C>T (p.Gln482Ter)	PCNT	Pathogenic	criteria provided, single submitter
1343402	NM_006031.6(PCNT):c.5059_5060del (p.Asn1687fs)	PCNT	Pathogenic	criteria provided, single submitter
1455235	NM_006031.6(PCNT):c.3019_3020del (p.Leu1007fs)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
1459821	NM_006031.6(PCNT):c.307C>T (p.Gln103Ter)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
159565	NM_006031.6(PCNT):c.1468C>T (p.Gln490Ter)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
159580	NM_006031.6(PCNT):c.2984_2994del (p.Ala995fs)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
159615	NM_006031.6(PCNT):c.5020G>T (p.Glu1674Ter)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
159621	NM_006031.6(PCNT):c.5578G>T (p.Glu1860Ter)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
159623	NM_006031.6(PCNT):c.5727_5736del (p.Leu1910fs)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
159663	NM_006031.6(PCNT):c.7796del (p.Leu2599fs)	PCNT	Pathogenic	criteria provided, single submitter
159677	NM_006031.6(PCNT):c.8868dup (p.Ala2957fs)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
159681	NM_006031.6(PCNT):c.8917C>T (p.Arg2973Ter)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
1805459	NM_006031.6(PCNT):c.8695C>T (p.Gln2899Ter)	PCNT	Pathogenic	criteria provided, single submitter
191168	NM_006031.6(PCNT):c.2374C>T (p.Arg792Ter)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
211844	NM_006031.6(PCNT):c.1714_1717del (p.Lys572fs)	PCNT	Pathogenic	criteria provided, single submitter
211864	NM_006031.6(PCNT):c.4938_4939del (p.Arg1646fs)	PCNT	Pathogenic	criteria provided, single submitter
224992	NM_006031.6(PCNT):c.2728C>T (p.Gln910Ter)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
225019	NM_006031.6(PCNT):c.3594_3598dup (p.Leu1200fs)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
2632726	NM_006031.6(PCNT):c.8593_8594del (p.Arg2865fs)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
2787786	NM_006031.6(PCNT):c.2990_2991dup (p.Glu998fs)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279984	NM_006031.6(PCNT):c.9535dup (p.Val3179fs)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2868691	NM_006031.6(PCNT):c.3424_3425del (p.Ser1142fs)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2957329	NM_006031.6(PCNT):c.9820del (p.Ser3274fs)	PCNT	Pathogenic	criteria provided, multiple submitters, no conflicts
2963720	NM_006031.6(PCNT):c.9870_9873del (p.Glu3290fs)	PCNT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
PCNT	Definitive	Autosomal recessive	microcephalic osteodysplastic primordial dwarfism type II	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PCNT	Orphanet:2637	Microcephalic osteodysplastic primordial dwarfism type II
PCNT	Orphanet:808	Seckel syndrome

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
PCNT	HGNC:16068	ENSG00000160299	O95613	Pericentrin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PCNT	Pericentrin	Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis.

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)
PCNT	Other/Unknown	no		PACT_domain, AKAP9/Pericentrin

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
body of tongue	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PCNT	283	ubiquitous	marker	gastrocnemius, body of tongue, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PCNT	3,934

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PCNT	O95613

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Chaperone Mediated Autophagy	1	496.5×	0.009	PCNT
Late endosomal microautophagy	1	326.3×	0.009	PCNT
Aggrephagy	1	248.3×	0.009	PCNT
Loss of Nlp from mitotic centrosomes	1	158.6×	0.009	PCNT
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.009	PCNT
AURKA Activation by TPX2	1	152.3×	0.009	PCNT
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.009	PCNT
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.009	PCNT
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.009	PCNT
Anchoring of the basal body to the plasma membrane	1	113.1×	0.009	PCNT

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
positive regulation of intracellular protein transport	1	674.1×	0.005	PCNT
microtubule nucleation	1	624.1×	0.005	PCNT
mitotic spindle organization	1	271.8×	0.007	PCNT
microtubule cytoskeleton organization	1	121.2×	0.012	PCNT
cilium assembly	1	73.6×	0.016	PCNT
signal transduction	1	16.1×	0.062	PCNT

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
PCNT	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	PCNT

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)
PCNT	0	—

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
NCT03139903	Not specified	COMPLETED	The Primordial Dwarfisms: Diagnosis, Identification of the Molecular Basis of Seckel Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II