Article

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.
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