Kennedy's Disease

Definition/Description

Kennedy’s Disease is a rare, X-linked recessive, genetic, progressive adult-onset neurodegenerative, neuromuscular disorder. In Kennedy’s Disease, both the spinal and bulbar neurons are affected, which causes muscle weakness and atrophy of the facial, bulbar, and limb muscles, while also causing sensory disturbances and endocrine abnormalities.

Synonyms:

• Kennedy’s syndrome

• Spinal bulbar muscular atrophy (SBMA)

• X-linked spinal bulbar muscular atrophy

Epidemiology

Kennedy’s Disease affects approximately 3.3/100,000 males. It very rarely affects females due to its X-linked transmission. Kennedy’s Disease usually appears between the ages of 30-60; however, earlier and later onsets can also occur.

Aetiology

Kennedy’s Disease is caused by a mutation of the gene that encodes for the androgen receptor (AR). The AR is in the cytoplasm of cells that make up the skin, kidney, prostate, skeletal muscle, and lower motor neurons in the spinal cord and brainstem. Normally, androgen hormones will bind to the AR, which initiates a cascade of reactions that signals genes to increase protein production for a number of functions within the cell. In Kennedy’s Disease, this function is compromised due to the mutation of the AR gene; nonetheless, the exact mechanism for motor neuron impairment remains unknown.

Clinical Manifestation

Extremities

• Weakness and wasting of facial, bulbar, and extremity muscles

• Limb weakness and wasting usually asymmetrical and weakness  proximal greater than distal impairment. More weakness on dominant side

• Weakness may present as difficulty climbing stairs and walking, particularly long distances

Tremors of the hands

• Reduced or absent tendon reflexes

• Hyperlordotic posture

• Internally rotated arms

• Gait disturbances, falls, or trouble with stairs

• Muscle cramps and fasciculations

• Myalgias

• Sensory abnormalities

Cerebrum

• Hanging jaw (jaw drop)

• Fasciculations of lips, perioral muscles, and tongue

• Irregular edges or deep furrowing in the midline of tongue

• Difficulty chewing

• Dysarthria

• Dysphagia

• Nasal voice due to palatal weakness

• Laryngospasm

• Twitching movements of chin

• Postural tremor of jaw

Endocrine

• Gynecomastia (most common)

• Reduced fertility due to testicular atrophy

• Azoospermia

• Oligospermia

• Androgen resistance

• Erectile dysfunction

• Reduced libido

• Diabetes

Fasciculations of lips and perioral muscles

• Tongue atrophy

• Difficulty chewing

• Vocal cord paresis resulting in dysarthria

• Pharyngeal paresis leading to dysphagia

• Nasal voice due to palatal weakness

Diagnosis

Diagnosis of Kennedy’s Disease is based on physical signs and symptoms previously listed in the Clinical Manifestations section.

Diagnosis of the disease can be confirmed by molecular genetic testing on a blood sample for cytosine-adenosin-guanosin (CAG) trinucleotide repeat expansion in the AR gene. Individuals with greater than 36 CAG trinucleotide repeats in the AR gene are diagnosed with Kennedy’s Disease.

Differential Diagnosis

ALS, spinal muscular atrophy with adult onset, adrenoleucodystrophy, hexosaminidase A deficiency, poliomyelitis

• Muscle diseases – fascioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, mitochondrial disorders, polymyositis, myasthenia gravis

• Neuropathies – hereditary sensory and autonomic neuropathy, multifocal motor neuropathy

• Non-neuromuscular conditions – hereditary spastic paraplegia, spinocerebellar ataxia, neurosyphillis, lead intoxication, aluminium intoxication, cervical spondylosis

Physiotherapy and Other Management

There is no proven treatment for Kennedy's disease and the effects of exercise is still uncertain, so the aim in Physiotherapy is to help manage the current symptoms and prevent complications experienced by the individual and to help in maintaining functional independence for as long as possible.

Physiotherapy interventions should be aimed at achieving the following:

• Maintaining muscle strength, soft tissue length, and joint range of motion

• Improving posture, balance, and coordination

• Maximising independence

• Reducing risk of falls

Physiotherapy intervention may include:

• Stretching exercises to lengthen shortened/tight muscles and maintain flexibility

• Strengthening exercises to aid in maintaining the ability to perform functional activities

• Core and trunk stabilization exercises

• Balance training

• Postural education – sitting, lying and standing

• Practicing functional activities such as standing and walking

• As the disease progresses, gait aid prescription may be necessary, which can improve ambulation and mobility

Strengthening exercises can include free weights, machine weights, and functional exercises using body weight. Exercises performed in a study by Chris Grunseich which saw an overall increase in lower extremity strength included knee extensions, squats, single leg stand, lunges, step ups and planks. The exercise parameters were adjusted throughout the 15 week program based on the individuals response to it. These exercises also resulted in an increased stride length and improved balance and coordination.

Resources

Kennedy’s Disease Association Website

Recent Related Research

Study identifies possible drug treatment for Kennedy’s Disease

Nisha M Badders et al. Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy, Nature Medicine (2018). DOI: 10.1038/nm.4500

References

Finsterer J. Bulbar and spinal muscular atrophy (Kennedy’s disease): a review. European journal of neurology. 2009 May 1;16(5):556-61.

Finsterer J. Perspectives of Kennedy's disease. Journal of the neurological sciences. 2010 Nov 15;298(1):1-0.

Kim, J., & La Spada, A. Rare Diseases [Internet]. Danbury, CT: National Organization for Rare Disorders; [publication date unknown]. Kennedy disease; [updated 2015; cited 2018 May 05]. Available from https://rarediseases.org/rare-diseases/kennedy-disease/

Greenland KJ, Zajac JD. Kennedy's disease: pathogenesis and clinical approaches. Internal medicine journal. 2004 May 1;34(5):279-86.

Grunseich C, Rinaldi C, Fischbeck KH. Spinal and bulbar muscular atrophy: pathogenesis and clinical management. Oral diseases. 2014 Jan 1;20(1):6-9.

Physio.co.uk [Internet]. Manchester, ENG: [publisher unknown], [publication date unknown]. Kennedy's disease; [ 2018 May 05], [location unknown]. Available from www.physio.co.uk/what-we-treat/neurological/conditions/kennedys-disease.php