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Kennedy disease(SMAX1)

MedGen UID:
333282
Concept ID:
C1839259
Disease or Syndrome
Synonyms: Bulbo-spinal atrophy X-linked; Bulbospinal neuronopathy X-linked recessive; Kennedy spinal and bulbar muscular atrophy; SMAX1; Spinal and Bulbar Muscular Atrophy; Spinal and bulbar muscular atrophy X-linked; SPINAL AND BULBAR MUSCULAR ATROPHY, X-LINKED 1
SNOMED CT: Kennedy syndrome (230253001); X-linked bulbospinal atrophy (230253001); Bulbospinal muscular atrophy (230253001)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): AR (Xq12)
 
Monarch Initiative: MONDO:0010735
OMIM®: 313200
Orphanet: ORPHA481

Disease characteristics

Excerpted from the GeneReview: Spinal and Bulbar Muscular Atrophy
Spinal and bulbar muscular atrophy (SBMA) is a gradually progressive neuromuscular disorder in which degeneration of lower motor neurons results in muscle weakness, muscle atrophy, and fasciculations in affected males. Affected individuals often show gynecomastia, testicular atrophy, and reduced fertility as a result of mild androgen insensitivity. [from GeneReviews]
Authors:
Albert La Spada   view full author information

Additional descriptions

From OMIM
Kennedy disease is an X-linked recessive form of spinal muscular atrophy. It occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. The disorder is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia (Harding et al., 1982). The disorder is clinically similar to, but genetically distinct from, classic forms of autosomal spinal muscular atrophy (see, e.g., SMA1; 253300).  http://www.omim.org/entry/313200
From MedlinePlus Genetics
Spinal and bulbar muscular atrophy, also known as Kennedy disease, is a disorder of specialized nerve cells that control muscle movement (motor neurons). These nerve cells originate in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem).

Spinal and bulbar muscular atrophy mainly affects males and is characterized by muscle weakness and wasting (atrophy) that usually begins in adulthood and worsens slowly over time. Muscle wasting in the arms and legs results in cramping; leg muscle weakness can also lead to difficulty walking and a tendency to fall. Certain muscles in the face and throat (bulbar muscles) are also affected, which causes progressive problems with swallowing and speech. Additionally, muscle twitches (fasciculations) are common. Some males with the disorder experience unusual breast development (gynecomastia) and may be unable to father a child (infertile).  https://medlineplus.gov/genetics/condition/spinal-and-bulbar-muscular-atrophy

Clinical features

From HPO
Testicular atrophy
MedGen UID:
57626
Concept ID:
C0156312
Disease or Syndrome
Wasting (atrophy) of the testicle (the male gonad) manifested by a decrease in size and potentially by a loss of fertility.
Decreased fertility
MedGen UID:
452706
Concept ID:
C0729353
Finding
Limb muscle weakness
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Sensory neuropathy
MedGen UID:
101791
Concept ID:
C0151313
Disease or Syndrome
Peripheral neuropathy affecting the sensory nerves.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Bulbar palsy
MedGen UID:
898626
Concept ID:
C4082299
Disease or Syndrome
Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Calf muscle hypertrophy
MedGen UID:
335868
Concept ID:
C1843057
Finding
Muscle hypertrophy affecting the calf muscles.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Abnormality of the mouth
MedGen UID:
6447
Concept ID:
C0026633
Congenital Abnormality
An abnormality of the mouth.
Gynecomastia
MedGen UID:
6694
Concept ID:
C0018418
Disease or Syndrome
Abnormal development of large mammary glands in males resulting in breast enlargement.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVKennedy disease
Follow this link to review classifications for Kennedy disease in Orphanet.

Professional guidelines

PubMed

Cai BC, Zhong LF, Liu YH, Sui ZY, Yang Q, Zeng DT, Li X, Xu WD, Chen T
Medicine (Baltimore) 2023 Apr 14;102(15):e33502. doi: 10.1097/MD.0000000000033502. PMID: 37058074Free PMC Article
Foster LA, Salajegheh MK
Am J Med 2019 Jan;132(1):32-37. Epub 2018 Aug 1 doi: 10.1016/j.amjmed.2018.07.012. PMID: 30075105
Fischbeck KH
Muscle Nerve 2013 Jun;47(6):789. Epub 2013 Mar 21 doi: 10.1002/mus.23814. PMID: 23408598Free PMC Article

Recent clinical studies

Etiology

Baskar D, Veeramani-Kumar P, Polavarapu K, Nashi S, Vengalil S, Menon D, Thomas A, Bhargava Sanka S, Muddasu Suhasini K, Huddar A, Unnikrishnan G, Bardhan M, Thomas PT, Manjunath N, Atchayaram N
Intern Med J 2024 Mar;54(3):455-460. Epub 2023 Aug 14 doi: 10.1111/imj.16205. PMID: 37578398
Müller KI, Nilssen Ø, Nebuchenykh M, Løseth S, Jonsrud C, Hoem G, Van Ghelue M, Arntzen KA
Neuromuscul Disord 2022 Jan;32(1):75-79. Epub 2021 Nov 19 doi: 10.1016/j.nmd.2021.11.007. PMID: 34922802
Pradat PF, Bernard E, Corcia P, Couratier P, Jublanc C, Querin G, Morélot Panzini C, Salachas F, Vial C, Wahbi K, Bede P, Desnuelle C; French Kennedy’s Disease Writing Group
Orphanet J Rare Dis 2020 Apr 10;15(1):90. doi: 10.1186/s13023-020-01366-z. PMID: 32276665Free PMC Article
Juntas Morales R, Pageot N, Taieb G, Camu W
Rev Neurol (Paris) 2017 May;173(5):308-319. Epub 2017 Apr 26 doi: 10.1016/j.neurol.2017.03.015. PMID: 28456383
Dahlqvist JR, Vissing J
J Mol Neurosci 2016 Mar;58(3):388-93. Epub 2015 Nov 19 doi: 10.1007/s12031-015-0686-3. PMID: 26585990

Diagnosis

Cai BC, Zhong LF, Liu YH, Sui ZY, Yang Q, Zeng DT, Li X, Xu WD, Chen T
Medicine (Baltimore) 2023 Apr 14;102(15):e33502. doi: 10.1097/MD.0000000000033502. PMID: 37058074Free PMC Article
Batista RL, Craveiro FL, Ramos RM, Mendonca BB
Endocr Pract 2022 Sep;28(9):911-917. Epub 2022 May 31 doi: 10.1016/j.eprac.2022.05.009. PMID: 35660466
Foster LA, Salajegheh MK
Am J Med 2019 Jan;132(1):32-37. Epub 2018 Aug 1 doi: 10.1016/j.amjmed.2018.07.012. PMID: 30075105
Querin G, Sorarù G, Pradat PF
Rev Neurol (Paris) 2017 May;173(5):326-337. Epub 2017 May 1 doi: 10.1016/j.neurol.2017.03.019. PMID: 28473226
Orsucci D, Rocchi A, Caldarazzo Ienco E, Alì G, LoGerfo A, Petrozzi L, Scarpelli M, Filosto M, Carlesi C, Siciliano G, Bonuccelli U, Mancuso M
Curr Mol Med 2014;14(5):598-602. doi: 10.2174/1566524014666140603100131. PMID: 24894177

Therapy

Pennuto M, Pradat PF, Sorarù G, Greensmith L; KD Consortium
Neuromuscul Disord 2024 May;38:8-19. Epub 2024 Mar 11 doi: 10.1016/j.nmd.2024.03.003. PMID: 38552412
Pareyson D, Fratta P, Pradat PF, Sorarù G, Finsterer J, Vissing J, Jokela ME, Udd B, Ludolph AC, Sagnelli A, Weydt P
J Mol Neurosci 2016 Mar;58(3):394-400. Epub 2016 Jan 7 doi: 10.1007/s12031-015-0704-5. PMID: 26744358
Dahlqvist JR, Vissing J
J Mol Neurosci 2016 Mar;58(3):388-93. Epub 2015 Nov 19 doi: 10.1007/s12031-015-0686-3. PMID: 26585990
Weydt P, Sagnelli A, Rosenbohm A, Fratta P, Pradat PF, Ludolph AC, Pareyson D
J Mol Neurosci 2016 Mar;58(3):379-87. Epub 2015 Nov 14 doi: 10.1007/s12031-015-0682-7. PMID: 26572537
Jöbsis GJ, Louwerse ES, de Visser M, Wolterman RA, Bolhuis PA, Busch HF, Brüggenwirth HT, Baas F, Wiersinga WM, Koelman JH
J Neurol Sci 1995 May;129 Suppl:56-7. doi: 10.1016/0022-510x(95)00064-9. PMID: 7595622

Prognosis

Baskar D, Veeramani-Kumar P, Polavarapu K, Nashi S, Vengalil S, Menon D, Thomas A, Bhargava Sanka S, Muddasu Suhasini K, Huddar A, Unnikrishnan G, Bardhan M, Thomas PT, Manjunath N, Atchayaram N
Intern Med J 2024 Mar;54(3):455-460. Epub 2023 Aug 14 doi: 10.1111/imj.16205. PMID: 37578398
Foster LA, Salajegheh MK
Am J Med 2019 Jan;132(1):32-37. Epub 2018 Aug 1 doi: 10.1016/j.amjmed.2018.07.012. PMID: 30075105
Querin G, Sorarù G, Pradat PF
Rev Neurol (Paris) 2017 May;173(5):326-337. Epub 2017 May 1 doi: 10.1016/j.neurol.2017.03.019. PMID: 28473226
Rodríguez Cruz PM, Pérez Sánchez JR, Catalina Álvarez I, Traba López A, Muñoz Blanco JL
J Clin Neuromuscul Dis 2014 Jun;15(4):164-6. doi: 10.1097/CND.0000000000000030. PMID: 24872216
Sperfeld AD, Karitzky J, Brummer D, Schreiber H, Häussler J, Ludolph AC, Hanemann CO
Arch Neurol 2002 Dec;59(12):1921-6. doi: 10.1001/archneur.59.12.1921. PMID: 12470181

Clinical prediction guides

Pradat PF, Bernard E, Corcia P, Couratier P, Jublanc C, Querin G, Morélot Panzini C, Salachas F, Vial C, Wahbi K, Bede P, Desnuelle C; French Kennedy’s Disease Writing Group
Orphanet J Rare Dis 2020 Apr 10;15(1):90. doi: 10.1186/s13023-020-01366-z. PMID: 32276665Free PMC Article
Rocchi C, Greco V, Urbani A, Di Giorgio A, Priori M, Massa R, Bernardi G, Marfia GA
Muscle Nerve 2011 Nov;44(5):737-40. doi: 10.1002/mus.22159. PMID: 22006688
Sinclair R, Greenland KJ, Egmond Sv, Hoedemaker C, Chapman A, Zajac JD
Br J Dermatol 2007 Aug;157(2):290-4. Epub 2007 Jun 26 doi: 10.1111/j.1365-2133.2007.08026.x. PMID: 17596176
Kassubek J, Juengling FD, Sperfeld AD
J Neurol Neurosurg Psychiatry 2007 Nov;78(11):1209-12. Epub 2007 Mar 1 doi: 10.1136/jnnp.2006.112532. PMID: 17332050Free PMC Article
Sperfeld AD, Hanemann CO, Ludolph AC, Kassubek J
Neurology 2005 Feb 22;64(4):753-4. doi: 10.1212/01.WNL.0000151978.74467.E7. PMID: 15728312

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