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

Typical: 20-49⁷; Range: 8⁸- 83⁹.

Association

Mendelian

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.

Detection

Although short-read sequencing screens have been used to detect this expansion⁴, sizing is generally validated with standard PCR fragment analysis or RP-PCR⁶.

Year

1991¹⁸; the first triplet disease to be discovered¹⁹

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

CAG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CAG

Pathogen. (gene)

CAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

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

Vérification de la connexion...

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)

Estimating the minimal clinically important difference of functional outcomes in spinal and bulbar muscular atrophy.

Matteo,Zanovello, Daniele,Sabbatini, Federica,Paredi, Alberto,Romito, Sara,Andreetta, Lorenzo,Blasi, Giulia,Musso, Angelo,Poletti, Rosario,Vasta, Manuela,Basso, Raffaele,Dubbioso, Maria,Pennuto, Giacomo Maria,Minicuci, Elena,Pegoraro, Luca,Bello, Gianni,Sorarù

Journal of neurology · 2026-07-31

pmid:42538437

A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha emitter 225Ac-J591 in patients with prostate cancer.

Scott T,Tagawa, Charlene,Thomas, Abdul Baseet,Arham, Aaron,Holmes, Valentina,Marulanda Corzo, Tobechukwu,Okobi, Shankar,Vallabhajosula, Vasilios,Avlonitis, Sandra,Huicochea Castellanos, Jones T,Nauseef, Elisabeth,O'Dwyer, Maham,Fatima, Peter,Gregos, Sarah,Yuan, Cora N,Sternberg, Ana,Molina, David M,Nanus, Neil H,Bander, Joseph,Osborne

Clinical cancer research : an official journal of the American Association for Cancer Research · 2026-07-22

pmid:42485097

Effect of androgen receptor polymorphism on hypogonadism severity and efficacy of testosterone replacement therapy.

Nelson W,Mills, Beatriz S,Hernandez, Peyton J,Coady, Arnaav,Walia, Gal,Saffati, Daniela Orozco,Rendon, Dalia,Khera, Nadia,Khera, Weitao,Song, Mohit,Khera

Translational andrology and urology · 2026-05-15

pmid:42436779

Striatal neuron dysfunction in C9ORF72-FTD/ALS is driven by AIS and potassium channel dysregulation.

Iris-Stefania,Pasniceanu, Manpreet S,Atwal, Cleide Dos,Santos Souza, Tobias,Moll, Marianne,King, Connie,Treanor, Daniel,Cabezas de la Fuente, Ryan J H,West, Laura,Ferraiuolo, Matthew R,Livesey

Cell reports · 2026-07-07

pmid:42412610

Icariin Attenuates Neuroinflammation and Dopaminergic Degeneration in a Rodent Model of Parkinson's Disease by Promoting the Expansion of Regulatory T Cells.

Sicong,Xu, Li,Jiang, Hao,Zhang, Ping,Zhang, Zhao,Pan

Frontiers in bioscience (Landmark edition) · 2026-06-26

pmid:42411473

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort.

Lara M,Lange, Catalina,Cerquera-Cleves, Ai Huey,Tan, Shen-Yang,Lim, Njideka U,Okubadejo, Chin-Hsien,Lin, Pin-Shiuan,Chen, Jung Hwan,Shin, Azlina,Ahmad-Annuar, Laurel A,Screven, Viorica,Chelban, Allison A,Dilliot, André,Fienemann, Kamalini Ghosh,Galvelis, Henry,Houlden, Hirotaka,Iwaki, Zane,Jaunmuktane, Patrick W,Cullinane, Thomas,Warner, Johanna,Junker, Yuliia,Kanana, Ignacio J Keller,Sarmiento, Christine,Klein, Pin-Jui,Kung, Hampton L,Leonard, Niccoló E,Mencacci, Mike A,Nalls, Raquel,Real, Samia Ben,Sassi, Joanne,Trinh, Dan,Vitale, Ana,Westenberger, Lesley Y,Wu, Andrew B,Singleton, Huw R,Morris, Katja,Lohmann, Cornelis,Blauwendraat, Peter,Heutink, Zih-Hua,Fang

medRxiv : the preprint server for health sciences · 2026-06-22

pmid:42396269

A Novel Patient-Derived Xenograft Model of Inflammatory Breast Cancer.

Princess,Ekpo, Monica,Khattak, Tiffany,Cheung, Yun Yun,Su, Pushpinder K,Bains, Ivan,Juric, Vladimir,Makarov, Daniel,Campo, Patrick,McIntire, Alexander,Ring, Gregor,Krings, Karin,List, James,Hicks, Michael F,Press, Ruth,Keri, Michael,Stanczyk, Gigi,Sengupta, Julie E,Lang

Research square · 2026-05-18

pmid:42239750

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

Limited Clinical Impact of Androgen Receptor Repeat Length (CAG and GGC) in Klinefelter Syndrome: A Multivariable Analysis.

Andrea,Graziani, Alberto,Scala, Maria Santa,Rocca, Cinzia,Vinanzi, Giuseppe,Grande, Andrea,Di Nisio, Riccardo,Selice, Antonella,Di Mambro, Alberto,Ferlin

Andrology · 2026-05-15

pmid:42138244

Locus SBMA AR

Disease

Locus

Alleles

gnomAD

References

Additional Literature