Continuum (Minneapolis, Minn.) · 2019
Facioscapulohumeral Muscular Dystrophies.
Клинический случайСтатьяОбзорНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wagner Kathryn R
Аннотация
PURPOSE OF REVIEW: Facioscapulohumeral muscular dystrophy (FSHD) is a common muscular dystrophy affecting both pediatric and adult patients. This article reviews the phenotype and pathophysiology of the disease as well as the recent efforts in clinical outcome measures and clinical trials.
RECENT FINDINGS: As the name implies, FSHD involves weakness of facial muscles, muscles that fix the scapula, and muscles overlying the humerus (biceps and triceps). The distinctive phenotype of FSHD occurs secondary to two different genetic mechanisms. FSHD type 1 (FSHD1) is due to a deletion on chromosome 4q, leading to hypomethylation and derepression of DUX4. FSHD type 2 (FSHD2) is due to mutations in SMCHD1 with resulting hypomethylation of the same subtelomeric region of chromosome 4q and derepression of DUX4. Understanding the central role of DUX4 has opened up the possibility of disease-modifying treatments. In preparation for clinical trials of novel agents, researchers are in the process of validating a number of clinical trial outcome measures including MRI, the 6-minute walk test, the FSHD Composite Outcome Measure, reachable workspace, electrical impedance myography, and the FSHD Health Index.
SUMMARY: The treatment of FSHD is currently supportive only. While past clinical trials in FSHD have been largely disappointing, novel agents in development, including antisense oligonucleotides, gene therapy, and small molecules, hold promise for future meaningful therapies.
RECENT FINDINGS: As the name implies, FSHD involves weakness of facial muscles, muscles that fix the scapula, and muscles overlying the humerus (biceps and triceps). The distinctive phenotype of FSHD occurs secondary to two different genetic mechanisms. FSHD type 1 (FSHD1) is due to a deletion on chromosome 4q, leading to hypomethylation and derepression of DUX4. FSHD type 2 (FSHD2) is due to mutations in SMCHD1 with resulting hypomethylation of the same subtelomeric region of chromosome 4q and derepression of DUX4. Understanding the central role of DUX4 has opened up the possibility of disease-modifying treatments. In preparation for clinical trials of novel agents, researchers are in the process of validating a number of clinical trial outcome measures including MRI, the 6-minute walk test, the FSHD Composite Outcome Measure, reachable workspace, electrical impedance myography, and the FSHD Health Index.
SUMMARY: The treatment of FSHD is currently supportive only. While past clinical trials in FSHD have been largely disappointing, novel agents in development, including antisense oligonucleotides, gene therapy, and small molecules, hold promise for future meaningful therapies.