1. Introduction

Kennedy’s disease, also known as Bulbar and spinal muscular atrophy (BSMA) is an adult-onset, X-linked recessive trinucleotide, polyglutamine disorder, caused by expansion of a polymorphic CAG tandem-repeat in exon 1 of the androgen-receptor (AR) gene on chromosome Xq11-12 ^[1]. Pathogenetically, mutated AR accumulates in nuclei and cytoplasm of motor neurons, resulting in their degeneration and loss ^[2]. Phenotypically, both muscle and motoneurons are affected, manifesting as weakness and wasting of the facial, bulbar and limb muscles, associated with endocrinologic disturbances ^{[3, 4, 5]}. There may be mild hyper-CK-emia, abnormal motor and sensory nerve conduction studies, and neuropathic and myopathic alterations on muscle biopsy.

The gold standard for diagnosing BSMA is genetic analysis, demonstrating a CAG-repeat number >40. No causal therapy is available, but symptomatic therapy should be provided for tremor, endocrinologic abnormalities, sensory disturbances, or muscle cramps. The course is slowly progressive, the ability to walk lost only late in life, only few patients require ventilatory support, and life expectancy only slightly reduced ^[2].

2. Case Presentation

A 60 year old, normotensive, non-diabetic, non-smoker, non-alcoholic male, mechanical engineer presented to us with the complaints of gradual onset and progressive difficulty in swallowing (more for liquid than solid together with nasal regurgitation) and nasal intonation of speech for 1 year. The patient also complained of generalized wasting of the muscles along with twitching for almost the same duration. He had difficulty in getting out of chair, climbing stairs, combing hairs and even eating foods. On query he admitted to have cramps long before the onset of his symptoms. There was no history of tingling, numbness, paresthesia, ocular problem or bladder bowel dysfunction. He does not give history of similar illness in any of his family members. On examination the patient is grossly emaciated, weighing 35 kg, having bilateral gynaecomastia (Figure 1). Neurological examination revealed a normal higher psychic function with a nasal intonation of speech. Cranial nerves examination revealed no abnormality except a wasted tongue with fasciculation (Figure 2) and an absent gag reflex (but normal palatal movement). Prominent fasciculation was noted in the facial muscles particularly in the masseter muscles. The jaw jerk was absent. Motor examination revealed bilateral postural tremor more on the right than left without any rigidity. The bulk of muscles is markedly reduced more in the proximal group than the distal with prominent fasciculation. The power is 3/5 in the proximal group and 4/5 in the distal groups in all limbs. All deep tendon reflexes were absent with bilateral flexor plantar response. All modalities of sensation were intact. There was no cerebellar sign or sign of meningeal irritation. Gait was normal. Other system examination revealed no abnormality except gynaecomastia bilaterally. Investigations revealed a modestly elevated serum CK (1603), normal brain and cervical spinal cord on MRI. NCS revealed reduced CMAP amplitude in the motor nerves and absent SNAP (Figure 3). Needle EMG revealed increased insertional activity, polyphasic, high amplitude, long duration MUAPs with reduced recruitment.

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Figure 1. Gynaecomastia and emaciation

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Figure 2. Wasted tongue

3. Discussion

Pathogenetically, mutated AR accumulates in nuclei and cytoplasm of motor neurons, resulting in their degeneration and loss. Phenotypically, patients present with amyotrophic, proximal or distal weakness and wasting of the facial, bulbar and limb muscles, occasionally sensory disturbances, and endocrinologic disturbances, such as androgen resistance, gynecomastia, elevated testosterone or progesterone, and reduced fertility. There may be mild hyper-CK-emia, abnormal motor and sensory nerve conduction studies, and neuropathic and myopathic alterations on muscle biopsy.

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Figure 3. (a) Reduced Median CMAP amplitude, (b) Absent Ulnar SNAP

The gold standard for diagnosing BSMA is genetic analysis, demonstrating a CAG-repeat number >40. The course is slowly progressive, the ability to walk lost only late in life, only few patients require ventilatory support, and life expectancy only slightly reduced. The diagnosis should be suspected in any male patient with motor neuron disease who presents with proximal and bulbar weakness, a positive family history, facial fasciculations, gynaecomastia and absence of signs of pyramidal tract disease (spasticity) and whose EDX studies show abnormal sensory studies in addition to the typical widespread neuropathic pattern on needle EMG ^{[6, 7]}. An unusually elevated CK level is often an important clue as well. The gold standard for diagnosing Kennedy’s disease is genetic analysis. We, therefore, performed the genetic analysis which established the case as Kennedy’s disease.

4. Conclusion

We presented this case because correct diagnosis is important both for prognosis and for its value in genetic counseling. Despite prominent bulbar weakness and the corresponding risk of aspiration, longevity usually is not affected.

References

[1]	Sinclair R, Greenland KJ, Egmond S, Hoedemaker C, Chapman A, Zajac JD. Men with Kennedy disease have a reduced risk of androgenetic alopecia. Br J Dermatol 2007; 157: 290-294.
	In article		View Article  PubMed
[2]	Finsterer J. Bulbar and spinal muscular atrophy (Kennedy’s disease): a review. European Journal of Neurology 2009; 16: 556-561.
	In article		View Article  PubMed
[3]	Jordan CL, Lieberman AP. Spinal and bulbar muscular atrophy: a motoneuron or muscle disease? Curr Opin Pharmacol 2008; 8: 752-758.
	In article		View Article  PubMed
[4]	Li XH, Zhuang JJ, Xie QY, et al. Clinical manifestations and molecular genetics of spinal bulbar muscular atrophy: report of 5 cases. Zhonghua Yi Xue Za Zhi 2007; 87: 1611-1615.
	In article		PubMed
[5]	Thomas PS Jr, Fraley GS, Damian V, et al. Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy. Hum Mol Genet 2006; 15: 2225-2238.
	In article		View Article  PubMed
[6]	Antonini G, Gragnani F, Romaniello A et al. Sensory involvement in spinal-bulbar muscular atrophy (Kennedy’s Disease). Muscle Nerve 2000; 23: 252-258.
	In article		View Article
[7]	Preston D C, Shapiro B E. Electromyography and Neuromuscular Disorders Clinical- Electrophysiologic Correlations. Third edition 2013: 435.
	In article