Inherited torticollis

Summary

Inherited torticollis (MONDO:0008583) is a disease with 2 cohort genes and 30 clinical trials. Top therapeutic interventions include botulinum toxin type a, daxibotulinumtoxina, and ibuprofen.

At a glance

• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited torticollis
Mondo ID	MONDO:0008583
MeSH	C535425
OMIM	189600
NCIT	C4811
SNOMED CT	268240006, 70070008
UMLS	C0040485
MedGen	11859
GARD	0004908
Is cancer (heuristic)	no

Also known as: congenital muscular torticollis · congenital torticollis · familial spasmodic torticollis · familial torticollis · fibromatosis colli · inherited torticollis (disease) · torticollis · torticollis, congenital · torticollis, familial

Data availability: 3 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › mesenchymal cell neoplasm › fibroblastic neoplasm › fibromatosis › inherited torticollis

Related subtypes (2): desmoid tumor, superficial Fibromatosis

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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
549661	NM_004301.5(ACTL6A):c.1129C>T (p.Arg377Trp)	ACTL6A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267823	46;XY;t(6;11)(q23;q21)or(q25;q21)dn		Uncertain significance	criteria provided, single submitter
523297	GRCh37/hg19 Xp22.13-22.12(chrX:19030055-19591281)	ADGRG2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTL6A	Orphanet:528084	Non-specific syndromic intellectual disability
ADGRG2	Orphanet:48	Congenital bilateral absence of vas deferens

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ACTL6A	HGNC:24124	ENSG00000136518	O96019	Actin-like protein 6A	clinvar
ADGRG2	HGNC:4516	ENSG00000173698	Q8IZP9	Adhesion G-protein coupled receptor G2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTL6A	Actin-like protein 6A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
ADGRG2	Adhesion G-protein coupled receptor G2	Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as dehydroepiandrosterone (DHEA; also named 3beta-hydroxyandrost-5-en-17-one) and androstenedione.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACTL6A	Other/Unknown	no		Actin, Actin_CS, ATPase_NBD
ADGRG2	GPCR	yes		GPS, GPCR_2_secretin-like, GPCR_2-like_7TM

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
calcaneal tendon	1
ganglionic eminence	1
primordial germ cell in gonad	1
caput epididymis	1
corpus epididymis	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTL6A	272	ubiquitous	marker	primordial germ cell in gonad, calcaneal tendon, ganglionic eminence
ADGRG2	182	broad	marker	corpus epididymis, caput epididymis, parotid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACTL6A	5,583
ADGRG2	723

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTL6A	O96019	25

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADGRG2	Q8IZP9	62.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. 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
Formation of the non-canonical BAF (ncBAF) complex	1	671.8×	0.010	ACTL6A
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.010	ACTL6A
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.010	ACTL6A
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.010	ACTL6A
Global Genome Nucleotide Excision Repair (GG-NER)	1	456.8×	0.010	ACTL6A
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.010	ACTL6A
Regulation of endogenous retroelements	1	368.4×	0.010	ACTL6A
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.010	ACTL6A
DNA Damage Recognition in GG-NER	1	285.5×	0.010	ACTL6A
Nucleotide Excision Repair	1	285.5×	0.010	ACTL6A
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.010	ACTL6A
MITF-M-dependent gene expression	1	181.3×	0.013	ACTL6A
RMTs methylate histone arginines	1	146.4×	0.014	ACTL6A
Transcriptional regulation by RUNX1	1	146.4×	0.014	ACTL6A
Deubiquitination	1	124.1×	0.014	ACTL6A
UCH proteinases	1	124.1×	0.014	ACTL6A
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	ACTL6A
MITF-M-regulated melanocyte development	1	114.2×	0.014	ACTL6A
DNA Repair	1	98.5×	0.016	ACTL6A
Chromatin organization	1	81.6×	0.017	ACTL6A
HATs acetylate histones	1	79.3×	0.017	ACTL6A
Chromatin modifying enzymes	1	72.3×	0.018	ACTL6A
Epigenetic regulation of gene expression	1	71.4×	0.018	ACTL6A
RNA Polymerase II Transcription	1	22.5×	0.054	ACTL6A
Post-translational protein modification	1	19.2×	0.060	ACTL6A
Gene expression (Transcription)	1	17.8×	0.063	ACTL6A
Generic Transcription Pathway	1	15.1×	0.071	ACTL6A
Developmental Biology	1	14.5×	0.072	ACTL6A
Metabolism of proteins	1	12.4×	0.081	ACTL6A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 telomere maintenance in response to DNA damage	1	561.7×	0.012	ACTL6A
regulation of DNA strand elongation	1	526.6×	0.012	ACTL6A
neural retina development	1	468.1×	0.012	ACTL6A
regulation of chromosome organization	1	468.1×	0.012	ACTL6A
blastocyst formation	1	383.0×	0.012	ACTL6A
regulation of G0 to G1 transition	1	337.0×	0.012	ACTL6A
regulation of nucleotide-excision repair	1	300.9×	0.012	ACTL6A
regulation of double-strand break repair	1	290.6×	0.012	ACTL6A
spinal cord development	1	255.3×	0.012	ACTL6A
regulation of mitotic metaphase/anaphase transition	1	247.8×	0.012	ACTL6A
positive regulation of T cell differentiation	1	227.7×	0.012	ACTL6A
positive regulation of double-strand break repair via homologous recombination	1	191.5×	0.012	ACTL6A
regulation of DNA replication	1	183.2×	0.012	ACTL6A
positive regulation of myoblast differentiation	1	183.2×	0.012	ACTL6A
positive regulation of DNA repair	1	179.3×	0.012	ACTL6A
positive regulation of stem cell population maintenance	1	172.0×	0.012	ACTL6A
positive regulation of double-strand break repair	1	172.0×	0.012	ACTL6A
DNA recombination	1	168.5×	0.012	ACTL6A
regulation of embryonic development	1	165.2×	0.012	ACTL6A
regulation of G1/S transition of mitotic cell cycle	1	153.2×	0.012	ACTL6A
negative regulation of cell differentiation	1	142.8×	0.012	ACTL6A
regulation of DNA repair	1	138.1×	0.012	ACTL6A
telomere maintenance	1	133.8×	0.012	ACTL6A
positive regulation of cell differentiation	1	133.8×	0.012	ACTL6A
spermatid development	1	72.6×	0.022	ADGRG2
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.023	ADGRG2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.026	ADGRG2
regulation of apoptotic process	1	41.7×	0.034	ACTL6A
regulation of cell cycle	1	37.3×	0.036	ACTL6A
chromatin remodeling	1	36.5×	0.036	ACTL6A

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACTL6A	1	2
ADGRG2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ACTL6A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ACTL6A	7	Binding:7
ADGRG2	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	ACTL6A

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	1	ACTL6A
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ADGRG2
E	Difficult family or no structure, no drug	0

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)
ADGRG2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 30.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	25
PHASE4	2
PHASE1	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01384214	PHASE4	COMPLETED	Effect of Botulinum Toxin Type A on Swallowing in Patients With Cervical Dystonia
NCT02651311	PHASE4	COMPLETED	Ultrasound Guided Intermediate Cervical Plexus Block for Congenital Muscular Torticollis
NCT02706795	PHASE2	COMPLETED	Dose-escalating Safety and Preliminary Efficacy of DaxibotulinumtoxinA for Injection in Cervical Dystonia
NCT00175604	PHASE1	WITHDRAWN	Comparative Trial of Botox in the Management of Children With Congenital Muscular Torticollis
NCT01041157	PHASE1	UNKNOWN	Botulinum Toxin Injection Efficiency
NCT05317390	Not specified	RECRUITING	Clinical Validation of DystoniaNet Deep Learning Platform for Diagnosis of Isolated Dystonia
NCT05917678	Not specified	RECRUITING	Effectiveness of Repositioning and Cranial Remolding in Infants With Cranial Deformation
NCT06474741	Not specified	NOT_YET_RECRUITING	Using Technology for Prediction and Prevention of Infant Torticollis and Plagiocephaly
NCT06901765	Not specified	NOT_YET_RECRUITING	Effectiveness of Kinesio Taping in Patients with Congenital Muscular Torticollis
NCT06957522	Not specified	NOT_YET_RECRUITING	Comparison of the Effectiveness of Face to Face Rehabilitation and Telerehabilitation in Infants With Congenital Muscular Torticollis
NCT00072956	Not specified	COMPLETED	The Physiology of Tricks
NCT00347334	Not specified	COMPLETED	Is Home Positioning Time Associated With Torticollis Rate of Recovery?
NCT00535938	Not specified	COMPLETED	MDs on Botox Utility (MOBILITY)
NCT00879450	Not specified	TERMINATED	Evaluating the Impact of a New Complement to Physiotherapy Intervention for Positional Torticollis in Infants
NCT01056861	Not specified	COMPLETED	Effects of Botulinum Toxin in Cervical Dystonia
NCT01655862	Not specified	COMPLETED	A Prospective, Observational Study of Patients With Cervical Dystonia (Dystonie) Treated With OnabotulinumtoxinA
NCT02403011	Not specified	UNKNOWN	Investigating the Effectiveness of Mobilization on Congenital Muscular Torticollis and Deformational Plagiocephaly
NCT02824848	Not specified	TERMINATED	Perception-Action Approach vs. Passive Stretching for Infants With Congenital Muscular Torticollis
NCT02889705	Not specified	COMPLETED	Echotexture in Following Muscle Fibrosis
NCT02907801	Not specified	TERMINATED	Perception-Action Approach Intervention for Infants With Congenital Muscular Torticollis
NCT03266224	Not specified	COMPLETED	Digital Analysis of Ultrasonographic Images in Children With Wry Neck
NCT03270189	Not specified	TERMINATED	Effect of the Visual Information Change in Functional Dystonia
NCT03562260	Not specified	UNKNOWN	Bipolar Surgical Release in Congenital Muscular Torticollis
NCT04421898	Not specified	UNKNOWN	3D Characterisation of the Skull Base Deformation in Congenital Muscular Torticollis
NCT04672837	Not specified	UNKNOWN	Pediatric Integrative Manual Therapy in Babies With Deformational Plagiocephaly and Congenital Muscular Torticollis
NCT06015555	Not specified	COMPLETED	TAMO Therapy Versus Postural Control Exercise in Children With Congenital Muscular Torticollis
NCT06186323	Not specified	COMPLETED	Relationship Between Home Environment and Development in Children Diagnosed With Muscular Torticollis
NCT06225934	Not specified	UNKNOWN	The Effect of Home Exercise Programs Applied of Congenital Muscular Torticollis.
NCT06879314	Not specified	COMPLETED	Development in Children Diagnosed With Congenital Muscular Torticollis
NCT06901414	Not specified	COMPLETED	Birth Complications and Intrauterine Constraints in the Etiology of Congenital Muscular Torticollis: A Nationwide Registry Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BOTULINUM TOXIN TYPE A	4	2
DAXIBOTULINUMTOXINA	4	1
IBUPROFEN	4	1