SBMA AR

Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare X-linked recessive motor neuron disease characterized by proximal and bulbar muscle wasting¹.

Prevalence

1 30,000

1-2/100,000 (population-specific, higher in Finnish population, Canadian population)²; 1/30,000³; mutation frequency of 1:3182 10x more frequent than reported disease prevalence of 1 in 30,000⁴. Only documented in patients with European/Asian ancestry, including Scandinavian, English, Belgian, French, Italian, German, Polish, Spanish, Swiss, Moroccan, Turkish, Chinese, Japanese (more common because of a founder effect), East Indian (potentially related to Japanese founder mutation)⁵, Korean, and Vietnamese populations⁶.

Age of Onset Details

Typical: 20-49⁷, Range: 8⁸- 83⁹.

Locus

hg19

chrX:66765158-66765261

hg38

chrX:67545316-67545419

t2t

chrX:65975147-65975250

Details

Intermediate alleles indicate reduced penetrance⁶. Expansions larger than the pathogenic threshold in the AR gene should be evaluated carefully. Interruptions have not been observed in patient cases; it has been proposed that longer alleles with interruptions may not be pathogenic¹⁰. Non-canonical motif CAA observed¹¹. Expansions are also detected ten-fold more often in a general population than would be expected by disease prevalence⁴. Clinical evaluation and phenotypic matching may be necessary to determine diagnosis even in the presence of a pure expanded allele. It has been proposed that contractions may play a role in disease¹². Disease may be subclinical in females¹³, and can be clinically heterogeneous even within the same family¹⁴.

Mechanism

GoF

Polyglutamine alters protein conformation leading to gain-of-function neurodegeneration^15,16. Transcriptional dysregulation, axonal transport disruption, and mitochondrial dysfunction also play causative roles in the neurodegeneration¹⁷.

Year

1991¹⁸; the first triplet disease to be discovered¹⁹

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

GCA

Pathogenic (ref.)

GCA

Pathogenic (gene)

AGC

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0010735

Advancing Epidemiology and Genetic Approaches for the Treatment of Spinal and Bulbar Muscular Atrophy: Focus on Prevalence in the Indigenous Population of Western Canada.

Harry,Wilton-Clark, Ammar,Al-Aghbari, Jessica,Yang, Toshifumi,Yokota

Genes · 2023-08-17

pmid:37628685

Orphanet: Kennedy disease

orphanet:481

Unexpected frequency of the pathogenic AR CAG repeat expansion in the general population.

Matteo,Zanovello, Kristina,Ibáñez, Anna-Leigh,Brown, Prasanth,Sivakumar, Alessandro,Bombaci, Liana,Santos, Joke J F A,van Vugt, Giuseppe,Narzisi, Ramita,Karra, Sonja W,Scholz, Jinhui,Ding, J Raphael,Gibbs, Adriano,Chiò, Clifton,Dalgard, Ben,Weisburd, Michael G,Hanna, Linda,Greensmith, Hemali,Phatnani, Jan H,Veldink, Bryan J,Traynor, James,Polke, Henry,Houlden, Pietro,Fratta, Arianna,Tucci

Brain : a journal of neurology · 2023-07-03

pmid:36797998

Clinical spectrum, biochemical profile and disease progression of Kennedy disease in an Indian cohort.

Dipti,Baskar, Preethish,Veeramani-Kumar, Kiran,Polavarapu, Saraswati,Nashi, Seena,Vengalil, Deepak,Menon, Aneesha,Thomas, Sai,Bhargava Sanka, Keerthipriya,Muddasu Suhasini, Akshata,Huddar, Gopikrishnan,Unnikrishnan, Mainak,Bardhan, Priya Treesa,Thomas, Nisha,Manjunath, Nalini,Atchayaram

Internal medicine journal · 2023-08-14

pmid:37578398

Spinal and Bulbar Muscular Atrophy

Albert,La Spada

GeneReviews® · 1993-01-01

genereviews:NBK1333

Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world.

A,Lund, B,Udd, V,Juvonen, P M,Andersen, K,Cederquist, M,Davis, C,Gellera, C,Kölmel, L O,Ronnevi, A D,Sperfeld, S A,Sörensen, L,Tranebjaerg, L,Van Maldergem, M,Watanabe, M,Weber, L,Yeung, M L,Savontaus

European journal of human genetics : EJHG · 2001-06-01

pmid:11436124

A family with early-onset and rapidly progressive X-linked spinal and bulbar muscular atrophy.

A,Echaniz-Laguna, E,Rousso, M,Anheim, M,Cossée, C,Tranchant

Neurology · 2005-04-26

pmid:15851746

A Case of Very Late Onset Spinobulbar Muscular Atrophy with Normal Creatine Kinase

Joseph,Conway, Yuebing,Li, Sakhi,Bhansali

RRNMF Neuromuscular Journal · 2024-12-17

doi:10.17161/2tmg0f25

Sequencing analysis of the spinal bulbar muscular atrophy CAG expansion reveals absence of repeat interruptions.

Pietro,Fratta, Toby,Collins, Sally,Pemble, Suran,Nethisinghe, Anny,Devoy, Paola,Giunti, Mary G,Sweeney, Michael G,Hanna, Elizabeth M C,Fisher

Neurobiology of aging · 2013-09-13

pmid:24041967

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.

Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson

Science advances · 2022-03-04

pmid:35245110

CAG repeat contraction in the androgen receptor gene in three brothers with mental retardation.

R F,Kooy, E,Reyniers, K,Storm, L,Vits, D,van Velzen, P E,de Ruiter, A O,Brinkmann, A,de Paepe, P J,Willems

American journal of medical genetics · 1999-07-30

pmid:10398229

Kennedy disease in two sisters with biallelic CAG expansions of the androgen receptor gene.

Kai Ivar,Müller, Øivind,Nilssen, Maria,Nebuchenykh, Sissel,Løseth, Christoffer,Jonsrud, Gry,Hoem, Marijke,Van Ghelue, Kjell Arne,Arntzen

Neuromuscular disorders : NMD · 2021-11-19

pmid:34922802

Phenotypic differences in a large family with Kennedy's disease from the Middle Black Sea region of Turkey.

Hatice,Karaer, Yüksel,Kaplan, Semiha,Kurt, Asli,Gundogdu, Begüm,Erdoğan, Nazli A,Başak

Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases · 2010-01-01

pmid:20184516

Tandem repeats mediating genetic plasticity in health and disease.

Anthony J,Hannan

Nature reviews. Genetics · 2018-02-05

pmid:29398703

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

Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA).

Masahisa,Katsuno, Fumiaki,Tanaka, Hiroaki,Adachi, Haruhiko,Banno, Keisuke,Suzuki, Hirohisa,Watanabe, Gen,Sobue

Progress in neurobiology · 2012-05-15

pmid:22609045

Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy.

A R,La Spada, E M,Wilson, D B,Lubahn, A E,Harding, K H,Fischbeck

Nature · 1991-07-04

pmid:2062380

Bulbospinal muscular atrophy: Kennedy's disease.

Michael,Sinnreich, Christopher Jon,Klein

Archives of neurology · 2004-08-01

pmid:15313856

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)

PROTACs therapeutically target the polyglutamine androgen receptor in spinal and bulbar muscular atrophy models.

Agamjot,Sangotra, Satya L,Reddy, Curtis J,Kuo, Weiguo,Xiang, Diane E,Merry, Christopher,Grunseich, Shaomeng,Wang, Andrew P,Lieberman

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025-09-04

pmid:40912964

Pigs exposed to nitrogen, argon or carbon dioxide filled high-expansion foam: behavioural responses, stun process and blood lactate concentration.

C,Lindahl, E,Sindhøj, M A,Gerritzen, H G M,Reimert, C,Berg, M,Blad, A,Wallenbeck

Animal : an international journal of animal bioscience · 2025-06-09

pmid:40614362

Reanalysis of Next-Generation Sequencing Data to Detect Tandem Repeat Expansions in 1,106 Czech Probands With Neurologic Disease.

Alena,Musilova, Petra,Lassuthova, Anna,Uhrova Meszarosova, Barbora,Straka, Jana,Krejcikova, Anna,Berounska, Marketa,Vlckova, Zuzana,Musova, Dana,Safka Brozkova

Neurology. Genetics · 2025-06-25

pmid:40585427

Feasibility of repetitive transcranial magnetic stimulation on non-motor symptoms of spinocerebellar ataxia type 3: a secondary analysis of a randomized clinical trial.

Hua,Wu, Hao-Ling,Xu, Xia-Hua,Liu, Arif,Sikandar, Wei,Lin, Mao-Lin,Cui, Ming-Xia,Kang, Yi-Ru,Zheng, Shi-Rui,Gan, Liang-Liang,Qiu

Frontiers in neurology · 2025-05-23

pmid:40488202

Accurate Quantification of Mutant and Wild-Type polyQ Proteins Using Simple Western Capillary Immunoassays.

Bas,Röttgering, Janwillem,Testerink, Rudie,Weij, Chantal,Beekman, Nicole,Datson

Molecular neurobiology · 2025-05-31

pmid:40450087

Polyglutamine expansion induced dynamic misfolding of androgen receptor.

Laurens W H J,Heling, Vahid,Sheikhhassani, Julian,Ng, Morris,van Vliet, Alba,Jiménez-Panizo, Andrea,Alegre-Martí, Jaie,Woodard, Willeke,van Roon-Mom, Iain J,McEwan, Eva,Estébanez-Perpiñá, Alireza,Mashaghi

Protein science : a publication of the Protein Society · 2025-06-01

pmid:40371721

Neuromuscular junction transcriptome analysis of spinal and bulbar muscular atrophy mice implicates sarcomere gene expression and calcium flux dysregulation in disease pathogenesis.

Anastasia,Gromova, Byeonggu,Cha, Nhat,Nguyen, Diya,Garg, Connor,Coscolluela, Laura M,Strickland, David,Luong, Fabiana,Longo, Bryce L,Sopher, Mai K,ElMallah, Albert R,La Spada

Human molecular genetics · 2025-07-03

pmid:40366765

GGN repeat length of the androgen receptor gene is associated with antral follicle count in Chinese women undergoing controlled ovarian stimulation.

Xinyan,Liu, Qi,Fan, Mingfen,Deng, Yan,Xu, Jing,Guo, Ping,Cao, Canquan,Zhou, Yanwen,Xu

Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025-02-20

pmid:40031964

Generation of an induced pluripotent stem cell line from a Kennedy Disease patient with AR mutation.

Meng,Zhang, Rui,Liu, Pengpeng,Sun, Chengsen,Zhang, Jingdong,Wang, Changjiang,Li

Stem cell research · 2024-12-30

pmid:39755011