Thomsen and Becker disease

Summary

Thomsen and Becker disease (MONDO:0009710) is a disease with 1 cohort gene and 5 clinical trials. Top therapeutic interventions include lamotrigine, mexiletine, and ranolazine.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 15
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1	Worldwide	Validated
Point prevalence	1-9 / 100 000		Europe	Validated
Point prevalence	1-9 / 100 000	7.3	Finland	Validated
Point prevalence	1-9 / 1 000 000	0.9	Italy	Validated
Point prevalence	1-9 / 1 000 000	0.52	United Kingdom	Validated
Point prevalence	1-9 / 1 000 000	0.75	Netherlands	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0002486	Myotonia	Very frequent (80-99%)
HP:0003457	EMG abnormality	Very frequent (80-99%)
HP:0003552	Muscle stiffness	Very frequent (80-99%)
HP:0003740	Myotonia with warm-up phenomenon	Very frequent (80-99%)
HP:0100284	EMG: myotonic discharges	Very frequent (80-99%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0003712	Skeletal muscle hypertrophy	Frequent (30-79%)
HP:0002312	Clumsiness	Occasional (5-29%)
HP:0003394	Muscle spasm	Occasional (5-29%)
HP:0003458	EMG: myopathic abnormalities	Occasional (5-29%)
HP:0008872	Feeding difficulties in infancy	Occasional (5-29%)
HP:0009063	Progressive distal muscle weakness	Occasional (5-29%)
HP:0002015	Dysphagia	Very rare (<1-4%)
HP:0011675	Arrhythmia	Very rare (<1-4%)
HP:0031546	Cardiac conduction abnormality	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Thomsen and Becker disease
Mondo ID	MONDO:0009710
MeSH	D009224
Orphanet	614
DOID	DOID:2106
ICD-10-CM	G71.12
NCIT	C84912
SNOMED CT	726051002
GARD	0012301
MedDRA	10028655, 10043461
Is cancer (heuristic)	no

Also known as: myotonia congenita

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

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neuromuscular disease › muscular channelopathy › Thomsen and Becker disease

Related subtypes (11): Andersen-Tawil syndrome, Morvan syndrome, malignant hyperthermia of anesthesia, Isaac syndrome, RYR1-related myopathy, CNGB3-related retinopathy, SCN4A-related channelopathy, neurological muscular channelopathy due to a genetic sodium channel defect, neurological muscular channelopathy due to a genetic chloride channel defect, neurological muscular channelopathy due to a genetic calcium channel defect, neurological muscular channelopathy due to a genetic potassium channel defect

Subtypes (2): myotonia congenita, autosomal dominant, myotonia congenita, autosomal recessive

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2920749	NM_000083.3(CLCN1):c.[1444G>A];[1448G>A]		Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
CLCN1	Supportive	Autosomal dominant	Thomsen and Becker disease	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLCN1	Orphanet:614	Thomsen and Becker disease

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
CLCN1	HGNC:2019	ENSG00000188037	P35523	Chloride channel protein 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLCN1	Chloride channel protein 1	Voltage-gated chloride channel involved in skeletal muscle excitability.

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)
CLCN1	Other/Unknown	no		ClC, Cl_channel-1, Cl-channel_core

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
hindlimb stylopod muscle	1
skeletal muscle tissue of rectus abdominis	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLCN1	108	tissue_specific	marker	hindlimb stylopod muscle, triceps brachii, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLCN1	1,191

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLCN1	P35523	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Stimuli-sensing channels	1	135.9×	0.007	CLCN1

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
neuronal action potential propagation	1	1404.3×	0.003	CLCN1
chloride transport	1	455.5×	0.004	CLCN1
chloride transmembrane transport	1	237.3×	0.005	CLCN1
muscle contraction	1	208.1×	0.005	CLCN1

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
CLCN1	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	CLCN1

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)
CLCN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	2
Not specified	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01939561	PHASE3	COMPLETED	Lamotrigine as Treatment of Myotonia
NCT02336477	PHASE3	COMPLETED	Mexiletine and Non Dystrophic Myotonias
NCT02251457	PHASE1	COMPLETED	Study of Ranolazine in Myotonia Congenita, Paramyotonia Congenita and Myotonic Dystrophy Type 1
NCT00244413	Not specified	COMPLETED	Characteristics of Nondystrophic Myotonias
NCT04799366	Not specified	COMPLETED	Contractile Properties of Hypertrofic Muscles in Patients With Non-Dystrophic Myotonia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LAMOTRIGINE	4	1
MEXILETINE	4	1
RANOLAZINE	4	1