TY - JOUR
T1 - Kennedy disease (X-linked recessive bulbospinal neuronopathy)
T2 - A comprehensive review from pathophysiology to therapy
AU - Querin, G.
AU - Sorarù, G.
AU - Pradat, P. F.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
KW - Clinical trials
KW - Diagnosis
KW - Kennedy's disease
KW - Muscular involvement
KW - SBMA
KW - Systemic symptoms
UR - http://www.scopus.com/inward/record.url?scp=85018389937&partnerID=8YFLogxK
U2 - 10.1016/j.neurol.2017.03.019
DO - 10.1016/j.neurol.2017.03.019
M3 - Review article
C2 - 28473226
AN - SCOPUS:85018389937
SN - 0035-3787
VL - 173
SP - 326
EP - 337
JO - Revue Neurologique
JF - Revue Neurologique
IS - 5
ER -