X-linked spinal and bulbar muscular atrophy (Kennedy's disease): the first case described in the Brazilian Amazon.

The X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is a rare X-linked, recessive, lower motor neuron disease, characterized by weakness, atrophy, and fasciculations of the appendicular and bulbar muscle. The disease is caused by an expansion of the CAG repetition in the androgen receptor gene. Patients with Kennedy's disease have more than 39 CAG repetitions. We report a case of 57-year-old man, resident of Monte Dourado (PA, Brazil) who complained of brachiocrural paresis evolving for 3 years along with fasciculations and tremors of extremities. In addition, he also developed dysarthria, dysphagia, and sexual dysfunction. The patient clinical picture included gait impairment, global hyporeflexia, proximal muscle atrophy of upper limbs, deviation of the uvula to right during phonation and tongue atrophy with fasciculations. The patient reported that about 30 years ago he had undergone gynecomastia surgery. His electroneuromyography suggested spinal muscular atrophy, and nuclear magnetic resonance imaging showed tapering of the cervical and thoracic spinal cord. Patient's creatine kinase level was elevated. In view of the findings, an exam was requested to investigate Kennedy's disease. The exam identified 46 CAG repetitions in the androgen receptor gene, which confirmed the diagnostic suspicion. This was the first case of Kennedy's disease diagnosed and described in the Brazilian Amazon. To our knowledge only other four papers were published on this disease in Brazilian patients. A brief review is also provided on etiopathogenic, clinical and diagnostic aspects.

X-linked spinal and bulbar muscular atrophy (Kennedy's disease): the first case described in the Brazilian Amazon / Atrofia muscular bulboespinhal ligada ao cromossomo X (doença de Kennedy): o primeiro caso descrito na Amazônia brasileira

ABSTRACT The X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is a rare X-linked, recessive, lower motor neuron disease, characterized by weakness, atrophy, and fasciculations of the appendicular and bulbar muscle. The disease is caused by an expansion of the CAG repetition in the androgen receptor gene. Patients with Kennedy's disease have more than 39 CAG repetitions. We report a case of 57-year-old man, resident of Monte Dourado (PA, Brazil) who complained of brachiocrural paresis evolving for 3 years along with fasciculations and tremors of extremities. In addition, he also developed dysarthria, dysphagia, and sexual dysfunction. The patient clinical picture included gait impairment, global hyporeflexia, proximal muscle atrophy of upper limbs, deviation of the uvula to right during phonation and tongue atrophy with fasciculations. The patient reported that about 30 years ago he had undergone gynecomastia surgery. His electroneuromyography suggested spinal muscular atrophy, and nuclear magnetic resonance imaging showed tapering of the cervical and thoracic spinal cord. Patient's creatine kinase level was elevated. In view of the findings, an exam was requested to investigate Kennedy's disease. The exam identified 46 CAG repetitions in the androgen receptor gene, which confirmed the diagnostic suspicion. This was the first case of Kennedy's disease diagnosed and described in the Brazilian Amazon. To our knowledge only other four papers were published on this disease in Brazilian patients. A brief review is also provided on etiopathogenic, clinical and diagnostic aspects.

RESUMO A atrofia muscular bulboespinhal ligada ao cromossomo X (doença de Kennedy) é uma rara doença de neurônio motor inferior, recessiva, ligada ao X, e caracterizada por fraqueza, atrofia e fasciculações da musculatura apendicular e bulbar. É causada por uma expansão da repetição CAG no gene do receptor de androgênio. Pacientes com doença de Kennedy apresentam mais de 39 repetições CAG. O paciente deste relato era do sexo masculino, 57 anos, morador de Monte Dourado (PA, Brasil), com queixa de paresia braquiocrural há 3 anos, acompanhada de fasciculações e tremores de extremidades. Em seguida, ele desenvolveu disartria, disfagia e disfunção sexual. Também apresentava comprometimento da marcha, hiporreflexia global, atrofia muscular proximal dos membros superiores, desvio da úvula para direita à fonação e atrofia de língua com fasciculações. Foi realizada cirurgia para tratamento de ginecomastia há 30 anos. A eletroneuromiografia sugeriu quadro de atrofia muscular espinhal. Imagens de ressonância magnética demonstraram afilamento da medula espinhal cervical e torácica. A creatina quinase estava elevada. Diante dos achados, solicitou-se investigação para doença de Kennedy, e foram identificadas 46 repetições CAG no gene do receptor de androgênio, o que confirmou a suspeita diagnóstica. Este foi o primeiro caso de doença de Kennedy diagnosticado e descrito na Amazônia brasileira. Existem, além deste relato, apenas outros quatro trabalhos publicados sobre a doença em pacientes do Brasil. Também realizamos breve revisão de aspectos etiopatogênicos, clínicos e diagnósticos.

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

Kennedy's disease, also known as spinal and bulbar muscular atrophy (SBMA), is a rare, adult-onset, X-linked recessive neuromuscular disease caused by expansion of a CAG repeat sequence in exon 1 of the androgen receptor gene (AR) encoding a polyglutamine (polyQ) tract. The polyQ-expanded AR accumulates in nuclei, and initiates degeneration and loss of motor neurons and dorsal root ganglia. While the disease has long been considered a pure lower motor neuron disease, recently, the presence of major hyper-creatine-kinase (CK)-emia and myopathic alterations on muscle biopsy has suggested the presence of a primary myopathy underlying a wide range of clinical manifestations. The disease, which affects male adults, is characterized by muscle weakness and atrophy localized proximally in the limbs, and bulbar involvement. Sensory disturbances are associated with the motor phenotype, but may be subclinical. The most frequent systemic symptom is gynecomastia related to androgen insensitivity, but other abnormalities, such as heart rhythm and urinary disturbances, have also been reported. The course of the disease is slowly progressive with normal life expectancy. The diagnosis of SBMA is based on genetic testing, with 38 CAG repeats taken as pathogenic. Despite several therapeutic attempts made in mouse models, no effective disease-modifying therapy is yet available, although symptomatic therapy is beneficial for the management of the weakness, fatigue and bulbar symptoms.

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

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.