Highlights of Kennedy ’ s Disease

C l i n M e d International Library Citation: Marengo AP, Guerrero Pérez F, Valera Yepes R, Villabona Artero C (2016) Highlights of Kennedy’s Disease. Int J Neurol Neurother 3:057. doi.org/10.23937/2378-3001/3/5/1057 Received: May 21, 2016: Accepted: September 20, 2016: Published: September 23, 2016 Copyright: © 2016 Pia MA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Pia et al. Int J Neurol Neurother 2016, 3:057

Women carrying the mutant AR allele are clinically unaffected, and they only show, in rare cases, abnormal electromyograms and the appearance of occasional muscle cramps and tremors in advance ages [2].It is possible that the physiological random inactivation of the X-chromosome in female may preserve at least 50% of total motoneurons, and this may be sufficient to maintain normal locomotor activity.However, in 2002, Schmidt, et al. [10] reported a study with two homozygous women for KD who did not show clinical signs of neurodegeneration.Thus the AR polyglutamine tract neurotoxicity may be activated in men by other factors, for instance the hormonal steroid testosterone [5].
The literature describes KD as a mild, late-onset, androgen resistance.With regards to this endocrine features, Dejager, et al. [1] studied 22 patients with KD.Nineteen of them showed clinical signs of partial androgen insensitivity; the most common feature was gynecomastia (mostly postpubertal), followed by under masculinization, testicular hypotrophy, or reduced fertility as defective spermatogenesis.Penis and prostate gland size were normal in all cases.
At our center, a small series of cases were recently reviewed by Valera Yepes, et al. [11].We reported 4 cases with typical neurological presentation, consisting of slowly progressing generalized muscle weakness with atrophy and bulbar muscle involvement.In all cases reported, molecular analysis showed an abnormal CAG triplet repeat expansion in AR gene.In our series the main symptom that motivated consultation was muscle weakness and fatigability of the lower limbs.The most common non-neurological manifestation was gynecomastia, as seen in Dejarger, et al. [1] study.Following gynecomastia, the most common features in our patients were reduced facial hair growth, testis hypotrophy, and decreased sexual interest.
The degree of androgen insensitivity is great enough to impair virilization or spermatogenesis, but is not great enough to impair normal male genital development.However, there may be subjects with androgen insensitivity with sufficient spermatogenesis to preserve fertility as seen in our series [11,12]; so the presence of progeny should not reduce the diagnosis suspicion.
It is important to notice that the endocrine symptoms can precede the appearance of the neurological symptoms, and thus the diagnosis of KD.

Letter to the Editor
Bulbar and spinal muscular atrophy, also called Kennedy's Disease (KD), is a very rare neurodegenerative disease, with onset in adult males usually in the fourth or fifth decade [1].Kennedy disease is named after William Kennedy, MD, who described this condition in 1968 [2].Twenty-five years ago, La Spada, et al. [3] demonstrated the genetic defect.International incidence is unknown [4], it has been estimated at 1:50,000 males [3]; however, is also believed to be underdiagnosed.
The pathogenesis of KD is the polymorphic CAG (cytosine, adenine, guanine) tandem-repeat expansion above 40 repeats in exon 1 of the androgen receptor (AR) gene on chromosome Xq11-12.In normal population the number of CAG codons usually ranges from 12 to 25, with an average size of 21-22.The polymorphism involving the CAD triplet repeat expansion of the AR gene, coding for a polyglutamine tract in the N-terminal transactivation domain of the AR protein, has been involved either in endocrine or neurological disorders.This hyperexpansion causes neurotoxicity, through misfolded protein toxicity.This disorder is characterized by death of motor neurons, mainly located in the anterior horns of the spinal cord and in the bulbar region [4].Besides the toxicity, there is a loss of AR function [5,6].Amato A, et al. [7] stated that genetic anticipation had not clearly been observed in KD.
The main neurological manifestations of KD are progressive muscle weakness, usually with an asymmetric distribution; and wasting of bulbar, facial and limb muscles [2].Presenting symptoms include postural tremor, proximal flaccid weakness, dysarthria, and fasciculation, which will run a slow progressive course [8].Some patients may also present with perioral fasciculation with variable bulbar paresis.The phenotypic features vary between asymptomatic biochemical alterations (such as creatine-kinase elevation) to severe muscle disease with bulbar involvement [2].There may be marked phenotypic heterogeneity within an affected family; the size of CAG repeat expansion significantly influences the age of disease onset and the severity of the disorder [9].
In conclusion, partial or mild androgen insensitivity syndrome is a consistent feature of KD.We need to raise medical awareness of the diagnosis suspicion of KD in all adult male with progressive muscle weakness and endocrine disorders associated with or without a family history.