Trismus-pseudocamptodactyly syndrome

Summary

Trismus-pseudocamptodactyly syndrome (MONDO:0008016) is a disease caused by MYH8 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: MYH8 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 123
• Phenotypes (HPO): 7

Clinical features

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0001376	Limitation of joint mobility	Very frequent (80-99%)
HP:0003011	Abnormality of the musculature	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0009773	Symphalangism affecting the phalanges of the hand	Very frequent (80-99%)
HP:0000303	Mandibular prognathia	Occasional (5-29%)
HP:0002827	Hip dislocation	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	trismus-pseudocamptodactyly syndrome
Mondo ID	MONDO:0008016
MeSH	C535857
OMIM	158300
Orphanet	3377
DOID	DOID:0111603
SNOMED CT	8757006
UMLS	C0265226
MedGen	78540
GARD	0002621
NORD	1795
Is cancer (heuristic)	no

Also known as: arthrogryposis distal type 7 · arthrogryposis, distal, type 7 · DA7 · distal arthrogryposis type 7 · Dutch-Kentucky syndrome · Hecht syndrome · Hecht-Beals syndrome · trismus-pseudocamptodactyly syndrome

Data availability: 123 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › distal arthrogryposis › trismus-pseudocamptodactyly syndrome

Related subtypes (22): arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome, arthrogryposis-like hand anomaly-sensorineural deafness syndrome, Gordon syndrome, congenital contractural arachnodactyly, arthrogryposis, distal, type 2E, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, Freeman-Sheldon syndrome, Sheldon-hall syndrome, Ehlers-Danlos syndrome, musculocontractural type, arthrogryposis-severe scoliosis syndrome, distal arthrogryposis type 5D, autism spectrum disorder - epilepsy - arthrogryposis syndrome, arthrogryposis, distal, with impaired proprioception and touch, digitotalar dysmorphism, distal arthrogryposis type 10, distal arthrogryposis Moore weaver type, arthrogryposis, distal, type 1C, arthrogryposis, distal, IIa 11, arthrogryposis-ectodermal dysplasia-other anomalies syndrome, ACTC1-related distal arthrogryposis with congenital heart disease, arthrogryposis, distal, type 2B4, arthrogryposis, distal, type 12

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

123 retrieved; paginated sample, class counts are floors:

75 uncertain significance, 19 conflicting classifications of pathogenicity, 12 benign/likely benign, 10 benign, 5 likely benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14136	NM_002472.3(MYH8):c.2021G>A (p.Arg674Gln)	MYH8	Pathogenic	criteria provided, multiple submitters, no conflicts
3906866	NM_002472.3(MYH8):c.2572G>T (p.Glu858Ter)	MYHAS	Likely pathogenic	criteria provided, single submitter
211564	NM_002472.3(MYH8):c.4042G>A (p.Glu1348Lys)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
321622	NM_002472.3(MYH8):c.5539G>A (p.Glu1847Lys)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
321625	NM_002472.3(MYH8):c.4994G>A (p.Arg1665Gln)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
321631	NM_002472.3(MYH8):c.4433G>A (p.Arg1478His)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
321645	NM_002472.3(MYH8):c.1833G>A (p.Leu611=)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
321655	NM_002472.3(MYH8):c.578G>A (p.Arg193His)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
397644	NM_002472.3(MYH8):c.1408del (p.Ile470fs)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
736252	NM_002472.3(MYH8):c.954G>C (p.Gln318His)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
769429	NM_002472.3(MYH8):c.4813G>A (p.Asp1605Asn)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
790329	NM_002472.3(MYH8):c.1318C>T (p.Leu440=)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885472	NM_002472.3(MYH8):c.-93T>G	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
887498	NM_002472.3(MYH8):c.676G>A (p.Ala226Thr)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
887563	NM_002472.3(MYH8):c.4147A>G (p.Ile1383Val)	MYH8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211563	NM_002472.3(MYH8):c.3532C>T (p.Arg1178Cys)	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211567	NM_002472.3(MYH8):c.5350C>G (p.Arg1784Gly)	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
321638	NM_002472.3(MYH8):c.3340T>C (p.Leu1114=)	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
757206	NM_002472.3(MYH8):c.539+1G>A	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
783773	NM_002472.3(MYH8):c.143C>T (p.Ser48Phe)	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
785554	NM_002472.3(MYH8):c.5459C>T (p.Ala1820Val)	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
321637	NM_002472.3(MYH8):c.3376G>C (p.Glu1126Gln)	LOC126862494	Uncertain significance	criteria provided, multiple submitters, no conflicts
321641	NM_002472.3(MYH8):c.2987C>G (p.Ser996Cys)	LOC126862494	Uncertain significance	criteria provided, single submitter
1806134	NM_002472.3(MYH8):c.2172-4G>T	MYH8	Uncertain significance	criteria provided, single submitter
225416	NM_002472.3(MYH8):c.3874C>T (p.Arg1292Ter)	MYH8	Uncertain significance	criteria provided, multiple submitters, no conflicts
321621	NM_002472.3(MYH8):c.5736G>C (p.Arg1912=)	MYH8	Uncertain significance	criteria provided, single submitter
321624	NM_002472.3(MYH8):c.5166+14A>G	MYH8	Uncertain significance	criteria provided, single submitter
321626	NM_002472.3(MYH8):c.4910G>A (p.Arg1637His)	MYH8	Uncertain significance	criteria provided, multiple submitters, no conflicts
321628	NM_002472.3(MYH8):c.4738G>A (p.Ala1580Thr)	MYH8	Uncertain significance	criteria provided, single submitter
321629	NM_002472.3(MYH8):c.4692C>A (p.Ile1564=)	MYH8	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
MYH8	Strong	Autosomal dominant	trismus-pseudocamptodactyly syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH8	Orphanet:319340	Carney complex-trismus-pseudocamptodactyly syndrome
MYH8	Orphanet:3377	Trismus-pseudocamptodactyly syndrome

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYH8	HGNC:7578	ENSG00000133020	P13535	Myosin-8	gencc,clinvar
MYHAS	HGNC:50609	ENSG00000272975		myosin heavy chain gene cluster antisense RNA	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH8	Myosin-8	Muscle contraction.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYH8	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
MYHAS	Other/Unknown	no

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
quadriceps femoris	1
skeletal muscle tissue of rectus abdominis	1
vastus lateralis	1
hindlimb stylopod muscle	1
muscle of leg	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH8	67	tissue_specific	marker	vastus lateralis, quadriceps femoris, skeletal muscle tissue of rectus abdominis
MYHAS	65	tissue_specific	yes	skeletal muscle tissue, hindlimb stylopod muscle, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH8	1,719
MYHAS	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYH8	P13535	75.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Striated Muscle Contraction	1	308.6×	0.006	MYH8
Muscle contraction	1	77.2×	0.013	MYH8

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
muscle filament sliding	1	1053.2×	0.003	MYH8
skeletal muscle contraction	1	510.7×	0.003	MYH8
ATP metabolic process	1	468.1×	0.003	MYH8
muscle contraction	1	208.1×	0.005	MYH8

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
MYH8	0	0
MYHAS	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	2	MYH8, MYHAS

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)
MYH8	0	—
MYHAS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.