Steinert disease, also known as myotonic dystrophy type 1, is a muscle disease characterized by myotonia and by multiorgan damage that combines various degrees of muscle weakness, arrhythmia and/or cardiac conduction disorders, cataract, endocrine damage, sleep disorders and baldness¹. It has also been linked to Autism and related traits, especially in individuals with earlier onset^2,3,4,5,6,7.

Prevalence

9.27 100,000

5-20/100,000⁸. 0.5-18.1/100,000⁹; 6.5/100,000¹⁰. 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000¹¹. Found across ethnicities/ancestries, with population-dependent prevalence⁸.

Age of Onset

Typical: 10-30⁸; Range: 0-74¹².

HPO Terms

HP:0000026 Male hypogonadism HP:0000029 Testicular atrophy HP:0000135 Hypogonadism HP:0000144 Decreased fertility HP:0000467 Neck muscle weakness HP:0000483 Astigmatism HP:0000518 Cataract HP:0000540 Hypermetropia HP:0000602 Ophthalmoplegia HP:0000708 Atypical behavior HP:0000712 Emotional lability HP:0000716 Depression HP:0000717 Autism HP:0000718 Aggressive behavior HP:0000729 Autistic behavior HP:0000736 Short attention span HP:0000739 Anxiety HP:0000802 Impotence HP:0000815 Hypergonadotropic hypogonadism HP:0000819 Diabetes mellitus HP:0000824 Decreased response to growth hormone stimulation test HP:0000842 Hyperinsulinemia HP:0000855 Insulin resistance HP:0000867 Secondary hyperparathyroidism HP:0001081 Cholelithiasis HP:0001249 Intellectual disability HP:0001252 Hypotonia HP:0001256 Mild intellectual disability HP:0001260 Dysarthria HP:0001262 Excessive daytime somnolence HP:0001263 Global developmental delay HP:0001268 Mental deterioration HP:0001288 Gait disturbance HP:0001290 Generalized hypotonia HP:0001319 Neonatal hypotonia HP:0001324 Muscle weakness HP:0001328 Specific learning disability HP:0001349 Facial diplegia HP:0001488 Bilateral ptosis HP:0001558 Decreased fetal movement HP:0001561 Polyhydramnios HP:0001596 Alopecia HP:0001644 Dilated cardiomyopathy HP:0001762 Talipes equinovarus HP:0002014 Diarrhea HP:0002015 Dysphagia HP:0002019 Constipation HP:0002059 Cerebral atrophy HP:0002093 Respiratory insufficiency HP:0002098 Respiratory distress HP:0002120 Cerebral cortical atrophy HP:0002234 Early balding HP:0002292 Frontal balding HP:0002460 Distal muscle weakness HP:0002486 Myotonia HP:0002494 Abnormal rapid eye movement sleep HP:0002500 Abnormal cerebral white matter morphology HP:0002527 Falls HP:0002540 Inability to walk HP:0002747 Respiratory insufficiency due to muscle weakness HP:0002870 Obstructive sleep apnea HP:0002878 Respiratory failure HP:0002910 Elevated circulating hepatic transaminase concentration HP:0002926 Abnormality of thyroid physiology HP:0003003 Colon cancer HP:0003124 Hypercholesterolemia HP:0003202 Skeletal muscle atrophy HP:0003326 Myalgia HP:0003477 Peripheral axonal neuropathy HP:0003547 Shoulder girdle muscle weakness HP:0003693 Distal amyotrophy HP:0003701 Proximal muscle weakness HP:0003722 Neck flexor weakness HP:0003740 Myotonia with warm-up phenomenon HP:0003749 Pelvic girdle muscle weakness HP:0004389 Intestinal pseudo-obstruction HP:0004749 Atrial flutter HP:0004755 Supraventricular tachycardia HP:0004887 Respiratory failure requiring assisted ventilation HP:0005110 Atrial fibrillation HP:0006677 Prolonged QRS complex HP:0006889 Borderline intellectual disability HP:0007010 Poor fine motor coordination HP:0007663 Reduced visual acuity HP:0007787 Posterior subcapsular cataract HP:0007941 Limited extraocular movements HP:0008069 Neoplasm of the skin HP:0008770 Obsessive-compulsive trait HP:0008872 Feeding difficulties in infancy HP:0009027 Foot dorsiflexor weakness HP:0009113 Diaphragmatic weakness HP:0009830 Peripheral neuropathy HP:0010794 Impaired visuospatial constructive cognition HP:0010804 Tented upper lip vermilion HP:0010864 Severe intellectual disability HP:0010952 Mild fetal ventriculomegaly HP:0011470 Nasogastric tube feeding in infancy HP:0011705 First degree atrioventricular block HP:0011999 Paranoia HP:0012054 Choroidal melanoma HP:0012114 Endometrial carcinoma HP:0012248 Prolonged PR interval HP:0012378 Fatigue HP:0012899 Handgrip myotonia HP:0012901 Myotonia of the jaw HP:0012903 Myotonia of the upper limb HP:0025169 Left ventricular systolic dysfunction HP:0025318 Ovarian carcinoma HP:0030192 Fatigable weakness of bulbar muscles HP:0030319 Weakness of facial musculature HP:0030692 Brain neoplasm HP:0031466 Impairment in personality functioning HP:0031546 Cardiac conduction abnormality HP:0040171 Decreased serum testosterone concentration HP:0040173 Abnormality of the tongue muscle HP:0040198 Non-medullary thyroid carcinoma HP:0100284 EMG: myotonic discharges HP:0100543 Cognitive impairment HP:0200136 Oral-pharyngeal dysphagia HP:0410011 Abnormality of masticatory muscle

Association

Mendelian

Locus

hg19 chr19:46273462-46273524

hg38 chr19:45770204-45770266

t2t chr19:48597739-48597756

Details

Intermediate alleles of 35-49 repeats are associated with premutation⁸. An estimated 3%-11% of DM1 expansions contain interruptions of CCG, CTC, CGG, GGC or CAG motifs^13,14; GCGGCA has also been reported¹⁵. In addition, an altered pattern of muscle involvement with proximal lower-limb weakness resembling DM2 has been reported in carriers of variant repeats, while multisystem involvement is comparable to that of pure expansions^16,17,18. Expansions within ZNF850 may function as DM1 modifiers¹⁹.

Mechanism

GoF

RNA gain-of-function: RNA gelation leading to misregulation of alternative splicing²⁰. Expanded DMPK r(CUG)n RNA forms a hairpin containing periodic 1*1 U/U internal loops that engage/sequester MBNL family RNA-binding proteins, especially MBNL1²¹, disrupting pre mRNA processing and contributing to cardiac phenotypes²². Loss of MBNL proteins has been linked to mis-splicing of Autism spectrum-risk genes such as SCN2A, ANK2, and SHANK2, possibly leading to Autism-related traits². Evidence suggests that disulfide bond-dependent MBNL1/MBNL2 dimerization maintains toxic RNA focal integrity^23,24. The vast majority of cases are maternally transmitted, though a rare case of paternal transmission has also been documented²⁵.

Detection

Flanking PCR has detected alleles up to ~150 repeats, while RP-PCR may detect missed expanded alleles^8,26. Southern blotting has approximated the size of large expansions²⁷, while long-read sequencing has resolved repeat size and structure²⁸.

Year

1992²⁹

Location in Gene

3' UTR

Gene Strand

Alleles

Ref. Motif

CAG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CAG

Pathogen. (gene)

CTG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0008056

Autism-related traits in myotonic dystrophy type 1 model mice are due to MBNL sequestration and RNA mis-splicing of autism-risk genes.

Łukasz J,Sznajder, Mahreen,Khan, Adam,Ciesiołka, Mariam,Tadross, Curtis A,Nutter, Katarzyna,Taylor, Christopher E,Pearson, Mark H,Lewis, Rochelle M,Hines, Maurice S,Swanson, Krzysztof,Sobczak, Ryan K C,Yuen

Nature neuroscience · 2025-04-21

pmid:40259070

Childhood-onset form of myotonic dystrophy type 1 and autism spectrum disorder: Is there comorbidity?

N,Angeard, E,Huerta, A,Jacquette, D,Cohen, J,Xavier, M,Gargiulo, L,Servais, B,Eymard, D,Héron

Neuromuscular disorders : NMD · 2017-12-15

pmid:29361396

Asperger syndrome associated with Steinert's myotonic dystrophy.

T A,Blondis, E,Cook, P,Koza-Taylor, T,Finn

Developmental medicine and child neurology · 1996-09-01

pmid:8810716

Expanded

Zuzana,Musova, Miroslava,Hancarova, Marketa,Havlovicova, Radka,Pourova, Michal,Hrdlicka, Josef,Kraus, Marie,Trkova, David,Stejskal, Zdenek,Sedlacek

Neuropsychiatric disease and treatment · 2016-09-19

pmid:27695335

Myotonic dystrophy type 1: clinical manifestations in children and adolescents.

Genevieve,Ho, Kate A,Carey, Michael,Cardamone, Michelle A,Farrar

Archives of disease in childhood · 2018-06-05

pmid:29871899

Cognitive function, behaviour and quality of life in children with myotonic dystrophy type 1 in South - Eastern Norway.

Petra,Aden, Anne-Britt,Skarbø, Sean,Wallace, Kristin,Ørstavik, Magnhild,Rasmussen

European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society · 2023-05-13

pmid:37209486

Myotonic Dystrophy Type 1

Thomas D.,Bird

GeneReviews® · 1993-01-01

genereviews:NBK1165

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care.

Marie,De Antonio, Céline,Dogan, Ferroudja,Daidj, Bruno,Eymard, Jack,Puymirat, Jean,Mathieu, Cynthia,Gagnon, Sandrine,Katsahian, Dalil,Hamroun, Guillaume,Bassez

Orphanet journal of rare diseases · 2019-06-03

pmid:31159885

Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis.

Qiao,Liao, Yihao,Zhang, Jian,He, Kun,Huang

Neuroepidemiology · 2022-04-28

pmid:35483324

Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

Huahua,Zhong, Li,Zeng, Xuefan,Yu, Qing,Ke, Jihong,Dong, Yan,Chen, Lijun,Luo, Xueli,Chang, Junhong,Guo, Yiqi,Wang, Hui,Xiong, Rongrong,Liu, Changxia,Liu, Jibao,Wu, Jie,Lin, Jianying,Xi, Wenhua,Zhu, Song,Tan, Fuchen,Liu, Jiahong,Lu, Chongbo,Zhao, Sushan,Luo

Orphanet journal of rare diseases · 2024-03-07

pmid:38454488

13pmid:27991661

Variant repeats within the

Jacob N,Miller, Ellen,van der Plas, Mark,Hamilton, Timothy R,Koscik, Laurie,Gutmann, Sarah A,Cumming, Darren G,Monckton, Peggy C,Nopoulos

Neurology. Genetics · 2020-08-12

pmid:32851192

Advancing molecular diagnostics of myotonic dystrophy type 1 using short-read whole genome sequencing.

Ingrid,Lojova, Marcel,Kucharik, Zuzana,Pös, Andrej,Balaz, Andrea,Zatkova, Eva,Tothova Tarova, Jaroslav,Budis, Ludevit,Kadasi, Tomas,Szemes, Jan,Radvanszky

Molecular and cellular probes · 2024-12-29

pmid:39710066

Atypical Phenotype of Myotonic Dystrophy Type 1 with Variant Repeats at the Age of Diagnosis.

Nemanja,Radovanovic, Jovan,Pesovic, Vanja,Viric, Nikola,Andrejic, Ivo,Bozovic, Goran,Brajuskovic, Dusanka,Savic-Pavicevic, Stojan,Peric

Biology · 2026-07-06

pmid:42450630

17pmid:31680381

18pmid:28689059

Identification of ZNF850 as a novel CTG repeat expansion-related gene in myotonic dystrophy type 1 patient-derived iPSCs.

Masayoshi,Kamon, Shuji,Wakatsuki, Masayuki,Nakamori, Masanori P,Takahashi, Madoka,Mori-Yoshimura, Hirofumi,Komaki, Toshiyuki,Araki

Human molecular genetics · 2025-02-08

pmid:39679849

Clinical and neuroimaging review of triplet repeat diseases.

Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe

Japanese journal of radiology · 2022-09-28

pmid:36169768

A chemoinformatics-guided platform for efficient discovery of RNA-binding small molecules: Proof-of-concept for myotonic dystrophy type 1.

Amirhossein,Taghavi, Jingsong,Shan, Xiyuan,Yao, Patrick R A,Zanon, Kisu,Sung, Álvaro,Simba-Lahuasi, Sylwia,Gorlach, Henning,Labuhn, David,Salthouse, Zhen,Wang, Adeline,Feri, Matthew D,Disney

bioRxiv : the preprint server for biology · 2026-05-11

pmid:42182465

MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model.

Rong-Chi,Hu, Yi,Zhang, Larissa,Nitschke, Sara J,Johnson, Ayrea E,Hurley, William R,Lagor, Zheng,Xia, Thomas A,Cooper

The Journal of clinical investigation · 2025-02-11

pmid:39932794

Muscleblind-like proteins dimerize by forming disulfide bonds to regulate alternative splicing and pathogenic RNA foci formation.

Luke A,Knudson, Adam,Kosti, Kathryn R,Moss, Liang,Shi, GiaLinh N,Nguyen, Aleksandra,Janusz-Kaminska, Eric X,Zhou, Ryan P,Hildebrandt, Eric T,Wang, Gary J,Bassell

bioRxiv : the preprint server for biology · 2026-03-26

pmid:41929128

Muscleblind-like proteins dimerize by forming disulfide bonds to regulate alternative splicing and pathogenic RNA foci formation.

Luke A,Knudson, Adam,Kosti, Ryan P,Hildebrandt, Ethan,Jennings, Eric X,Zhou, Kathryn R,Moss, Liang,Shi, GiaLinh N,Nguyen, Aleksandra,Janusz-Kaminska, Eric T,Wang, Gary J,Bassell

Nucleic acids research · 2026-05-20

pmid:42227335

Optical mapping reveals a higher level of large-scale structural variants in a family with paternally transmitted myotonic dystrophy and independent Parkinson's disease.

Md Mehedi,Hasan, Jenna,Craddock, Tingting,Gong, Ruth J,Lyons, Igor,Stevanovski, Sanjog R,Chintalaphani, Ira W,Deveson, Weerachai,Jaratlerdsiri, Kishore R,Kumar, Vanessa M,Hayes

The Journal of pathology · 2026-06-09

pmid:42261605

Detection of large expansions in myotonic dystrophy type 1 using triplet primed PCR.

Susmita,Singh, Amy,Zhang, Stephen,Dlouhy, Shaochun,Bai

Frontiers in genetics · 2014-04-24

pmid:24795756

Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2.

Erik-Jan,Kamsteeg, Wolfram,Kress, Claudio,Catalli, Jens M,Hertz, Martina,Witsch-Baumgartner, Michael F,Buckley, Baziel G M,van Engelen, Marianne,Schwartz, Hans,Scheffer

European journal of human genetics : EJHG · 2012-05-30

pmid:22643181

Targeted long-read sequencing for high-resolution repeat profiling in myotonic dystrophy type 1.

Yoojung,Han, Ja-Hyun,Jang, Hyeshik,Chang

Experimental & molecular medicine · 2026-04-13

pmid:41974889

Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member.

J D,Brook, M E,McCurrach, H G,Harley, A J,Buckler, D,Church, H,Aburatani, K,Hunter, V P,Stanton, J P,Thirion, T,Hudson

Cell · 1992-02-21

pmid:1310900

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Fatty-acid-based antimiR-23b delivery in the DMSXL model: A potential therapeutic strategy for brain dysfunction in myotonic dystrophy type 1.

Diego,Piqueras-Losilla, Andrea,Garcia-Rey, Aline,Huguet-Lachon, Argimiro,Mayoral-Olmos, Isabel,Campillo, Melanie,Nufer, Mouli,Chakraborty, Ana,Díaz-Maqueda, Nuria,Barquero, Anchel,Gonzalez-Barriga, José,Martinez-Hernandez, María Gracia,de Garnica García, Geneviève,Gourdon, Ruben,Artero, Beatriz,Llamusí, Estefanía,Cerro-Herreros

Cell reports. Medicine · 2026-07-22

pmid:42486096

Atypical Phenotype of Myotonic Dystrophy Type 1 with Variant Repeats at the Age of Diagnosis.

Nemanja,Radovanovic, Jovan,Pesovic, Vanja,Viric, Nikola,Andrejic, Ivo,Bozovic, Goran,Brajuskovic, Dusanka,Savic-Pavicevic, Stojan,Peric

Biology · 2026-07-06

pmid:42450630

Aberrant neuronal differentiation and splicing defects in Congenital Myotonic Dystrophy (DM1) iPSC models.

Surya Chandra Rao,Thumu, Jean Patrick,Gonzales, Soha,Munir, Connor,Tuck, Oscar,Dominguez, Sandeep K,Singh

bioRxiv : the preprint server for biology · 2026-07-01

pmid:42427665

Tissue-specific CTG•CAG expansion rate and disease severity are modified by DNA repair genes expression levels in myotonic dystrophy type 1 patients.

Melissa,Palma-Jiménez, Lisbeth,Ramirez-Carvajal, Hailey,Olafson, Eric T,Wang, Fernando,Morales

DNA repair · 2026-07-07

pmid:42419013

Neurofilament light chain reflects motor impairment in myotonic dystrophy type 1.

Chul Hwi,Shin, Incheol,Seo, Ye-Ri,Kim, Jin-Mo,Park, Jin-Sung,Park

Frontiers in neurology · 2026-05-26

pmid:42273033

Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.

Zakhiriddin,Khojakulov, Robin J,Palvadeau, Müge,Kovancılar-Koç, Irmak,Atay, Irmak,Şahbaz, Şeyma,Tekgül, Ayça,Şahin, Esmer Zeynep Duru,Badakal, Tuğçe,Gül-Demirkale, Vildan,Çiftçi, Elif,Bayraktar, Ceren,Tunca, Natalia,Smolina, Fulya,Akçimen, Ayşe Nazlı,Başak

International journal of molecular sciences · 2026-05-13

pmid:42196324

Generation of iPSC lines from myotonic dystrophy type 1 patients with varying CTG repeat lengths.

Thomas D,Hoekman, Lisa,Rahm, Silvia,Albert, Derick G,Wansink, Hans,van Bokhoven, Renée H L,Raaijmakers

Stem cell research · 2026-05-10

pmid:42133999

Targeted long-read sequencing for high-resolution repeat profiling in myotonic dystrophy type 1.

Yoojung,Han, Ja-Hyun,Jang, Hyeshik,Chang

Experimental & molecular medicine · 2026-04-13

pmid:41974889

Population-scale repeat expansions elucidate disease risk and brain atrophy.

Vijay Kumar,Pounraja, Jae Hoon,Sul, Joseph,Herman, Sean,O'Keeffe, Veera,Rajagopal, Xiaodong,Bai, Michael D,Kessler, Neelroop,Parikshak, Karl,Landheer, Xingmin,Zhang, Sean,Yu, Lance,Zhang, Michelle G,LeBlanc, Jennifer,Rico-Varela, Frederic,Grau, Sarah,Wolf, Sriramkumar,Sundaramoorthy, Farshid,Sepehrband, Eli A,Stahl, Yuda,Huo, Mohsin,Ahmed, Susan,Croll, William,Salerno, John D,Overton, Jonathan,Marchini, Jeffrey,Reid, Luca A,Lotta, Aris,Baras, Goncalo R,Abecasis, Giovanni,Coppola, Sahar,Gelfman

Nature · 2026-04-08

pmid:41951733

Locus DM1 DMPK

Disease

Locus

Alleles

gnomAD

References

Additional Literature