Onset Manifestations of Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease)

Abstract

Spinal and bulbar muscular atrophy (SBMA) is regarded as a disorder with adult onset between third and fifth decade of life. However, there is increasing evidence that SBMA may start already before adulthood. The present study investigated the following: (1) Which clinical manifestations have been described so far in the literature as initial manifestations? (2) Which was the age at onset of these manifestations? and (3) Is age at onset dependent on the CAG-repeat length if non-motor manifestations are additionally considered? Data for this review were identified by searches of MEDLINE using appropriate search terms. Onset manifestations in SBMA can be classified as frequent, rare, motor, non-motor, or questionable. Frequent are muscle weakness, cramps, fasciculations/twitching, tremor, dysarthria, dysphagia, or gynecomastia. Rare are myalgia, easy fatigability, exercise intolerance, polyneuropathy, hyper-CKemia, under-masculinized genitalia, scrotal hypospadias, microphallus, laryngospasm, or oligospermia. Questionable manifestations include sensory disturbances, cognitive impairment, increased pituitary volume, diabetes, reduced tongue pressure, elevated creatine-kinase, or low androgens/high estrogens. Age at onset is highly variable ranging from 4-76 years. Non-motor manifestations develop usually before motor manifestations. Age at onset depends on what is considered as an onset manifestation. Considering non-motor onset manifestations, age at onset is independent of the CAG-repeat size. In conclusion, age at onset of SBMA depends on what is regarded as onset manifestation. If non-motor manifestations are additionally considered, age at onset is independent of the CAG-repeat length. Since life expectancy is hardly reduced in SBMA, re-investigation of patients from published studies with regard to their initial disease profiles is recommended.

Disease progression and outcome measures in spinobulbar muscular atrophy

“…1 The expanded CAG repeat length causes a testosterone-dependent toxic gain of function of the androgen receptor that affects both neurons and muscle. 1 The expanded CAG repeat length causes a testosterone-dependent toxic gain of function of the androgen receptor that affects both neurons and muscle.…”

Kennedy disease (X-linked recessive bulbospinal neuronopathy): A comprehensive review from pathophysiology to therapy

“…However, more recently, it has been highlighted that other slighter symptoms are often present long time before the onset of muscular weakness. More specifically, these symptoms may be hand tremors, muscular cramps, myalgias, breast enlargement, premature exhausting during physical exercise and feet numbness [11].…”

“…The sequential use of walking aids (handrail, cane, frame, and wheelchair), bulbar-related symptoms (dysarthria and dysphagia), and erectile dysfunction are reported between the ages of 50 and 60 years. Since lower limbs' proximal muscles are predominantly affected, a particular feature of SBMA is the difficulty in stairs climbing and in rising up from a chair [11].…”

“…The diminution of amplitude of the sensory action potentials, in the context of a MND, is suggestive of SBMA. Sensory abnormalities are found in 72 % to 100 % of SBMA patients [6,10,11].…”

Introduction to the Special Issue on Spinal and Bulbar Muscular Atrophy

“…The paper by Josef Finsterer and Gianni Sorarù entitled "Onset manifestations of spinal and bulbar muscular atrophy (Kennedy disease)" (Finsterer and Soraru 2015) addresses open questions in the clinical profiling of SBMA. There is indeed a critical need to establish which clinical symptoms better define the onset of disease and whether the age of onset is directly correlated to the length of the CAG expansion when non-motor symptoms are taken into account.…”