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.

HPO Terms

–

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 expansion [@pmid:36797998], sizing is generally validated with standard PCR fragment analysis or RP-PCR [@genereviews:NBK1333].

Year

1991¹⁸; the first triplet disease to be discovered¹⁹

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

GCA

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GCA

Pathogenic (gene)

AGC

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (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)

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

Progressive Proximal Muscle Weakness Due to a 51 CAG Repeat Expansion in Exon 1 of the Androgen Receptor Gene: A Case Report of Kennedy Disease.

Nguyen,Thi Tuong Vi, Nguyen,Huu Thanh, Dong,Thi Bien, Nguyen,Hong Quan

The American journal of case reports · 2026-05-03

pmid:42070078

Reliability and construct validity of the Italian version of AMAT scale in SBMA subjects.

Elisabetta,Pupillo, Elisa,Bianchi, Maurizio A,Leone, Sabrina,Paganoni, Alberto,Romito, Federica,Paredi, Giacomo Maria,Minicuci, Gianni,Sorarù

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026-05-02

pmid:42067676

Short tandem repeat expansions in patients with neurodegenerative dementia.

Yuan,Zhu, Xuewen,Xiao, Yiliang,Liu, Zheng,Wang, Tengfei,Luo, Tianyan,Xu, Qijie,Yang, Xiaoli,Hao, Cong,Zhang, Sizhe,Zhang, Shilin,Luo, Yafang,Zhou, Xinxin,Liao, Yun,Tian, Ling,Weng, Liangjuan,Fang, Beisha,Tang, Bin,Jiao, Jinchen,Li, Lu,Shen

EBioMedicine · 2026-02-26

pmid:41762523

The alternative androgen receptor isoform A mitigates toxicity of polyglutamine-elongated mutant androgen receptor in spinal and bulbar muscular atrophy.

Marta,Chierichetti, Roberta,Andreotti, Barbara,Tedesco, Veronica,Ferrari, Laura,Cornaggia, Paola,Pramaggiore, Marta,Cozzi, Ali,Mohamed, Rocio,Magdalena, Margherita,Piccolella, Giulia,Boarolo, Valeria,Crippa, Paola,Rusmini, Mariarita,Galbiati, Carlo,Rinaldi, Eric N,Anderson, Udai Bhan,Pandey, Maria,Pennuto, Riccardo,Cristofani, Angelo,Poletti

Journal of advanced research · 2026-01-19

pmid:41564929

An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.

Kentaro,Maeda, Tomoki,Hirunagi, Kentaro,Sahashi, Yukiko,Kamiya, Madoka,Iida, Kenji,Sakakibara, Kazunari,Onodera, Manabu,Ohyama, Yohei,Okada, Hideyuki,Okano, Hiroyuki,Asanuma, Masahisa,Katsuno

Molecular therapy. Nucleic acids · 2025-12-11

pmid:41552385

Heterogeneous phenotype and cardiovascular comorbidities in Swedish patients with spinobulbar muscular atrophy.

Anna-Karin,Roos, Simon,Forsberg, Erica,Stenvall, Peter M,Andersen, Per,Zetterström, Angelica,Nordin, Karin M E,Forsberg

Journal of neurology · 2026-01-10

pmid:41513898

Correlation between inflammatory burden index and hemorrhage expansion among large-artery atherosclerosis acute ischemic stroke with hemorrhagic transformation.

Yi,Yang, YanFei,Han, Shen,Shen, MengXia,Wan, Mitchell,Wu, YongBo,Zhang

BMC neurology · 2025-12-08

pmid:41361869

Locus SBMA AR

Disease

Locus

Alleles

gnomAD

References

Additional Literature