Facioscapulohumeral dystrophy (FSHD) is associated with somatic chromatin relaxation of the D4Z4 repeat array and derepression of the D4Z4-encoded DUX4 retrogene coding for a germline transcription factor. Somatic DUX4 derepression is caused either by a 1-10 unit repeat-array contraction (FSHD1) or by mutations in SMCHD1, which encodes a chromatin repressor that binds to D4Z4 (FSHD2). Here, we show that heterozygous mutations in DNA methyltransferase 3B (DNMT3B) are a likely cause of D4Z4 derepression associated with low levels of DUX4 expression from the D4Z4 repeat and increased penetrance of FSHD. Recessive mutations in DNMT3B were previously shown to cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome. This study suggests that transcription of DUX4 in somatic cells is modified by variations in its epigenetic state and provides a basis for understanding the reduced penetrance of FSHD within families.

Moderate-intensity strength training in myotonic dystrophy and FSHD and aerobic exercise training in dermatomyositis and polymyositis and myotonic dystrophy type I appear to do no harm, but there is insufficient evidence to conclude that they offer benefit. In mitochondrial myopathy, aerobic exercise combined with strength training appears to be safe and may be effective in increasing submaximal endurance capacity. Limitations in the design of studies in other muscle diseases prevent more general conclusions in these disorders.

In FSHD strength training and albuterol appear safe interventions with limited positive effect on muscle strength and volume. Consequences of prolonged use are presently unclear, which precludes routine prescription.

Respiratory insufficiency due to respiratory muscle weakness is a common complication of many neuromuscular diseases. The prevalence of respiratory failure in facioscapulohumeral muscular dystrophy (FSHD) is unknown. The authors identified 10 FSHD patients on nocturnal ventilatory support at home, representing approximately 1% of the Dutch FSHD population. Severe muscle disease, wheelchair dependency, and kyphoscoliosis appeared to be risk factors for respiratory failure.

Spirometry and maximal respiratory pressures are pulmonary function parameters commonly used to evaluate respiratory function. Prediction values are available for conventional lung function devices using a standard tube or flanged type of mouthpiece connection. This equipment is not suitable for patients with facial or buccal muscle weakness, because of air leakage around the mouthpiece. A face mask was used for the portable lung function devices used in the neuromuscular department.The aim of this study was to compare the face mask and the conventional mouthpiece for the measurement of spirometry and of respiratory pressures in 22 healthy subjects.Values obtained with the conventional mouthpiece differed significantly from values obtained with the face mask. With the mask, forced vital capacity and forced expiratory volume in one second were 200 mL lower, and maximal expiratory pressure was 3.2 kPa lower than with the mouthpiece. Subsequently, new prediction values for face mask spirometry and maximal respiratory pressures were obtained from 252 other healthy subjects, from which new prediction equations were derived.It was concluded that the face mask connection to the lung function device is a valid alternative, is easy to use and is most useful to monitor changes in patients. This study confirms the importance of appropriate prediction equations, depending on subjectinstrument interfaces. Measurement of vital capacity (VC) and maximal respiratory pressures is commonly used to evaluate respiratory function and respiratory muscle strength in patients with chronic obstructive pulmonary disease or neuromuscular diseases [1][2][3]. Portable devices are useful for rapid and simple assessment of respiratory function in the office and at the bedside. Prediction values of spirometry and maximal respiratory pressures are available for portable and nonportable devices with a standard tube or a flanged type of mouthpiece connection [4][5][6][7][8]. This equipment is only suitable for subjects capable of making a good seal with their lips around the mouthpiece. However, patients with neuromuscular diseases characterised by facial or bulbar muscle weakness, e.g. amyotrophic lateral sclerosis, myasthenia gravis, myotonic dystrophy and facioscapulohumeral muscular dystrophy, often cannot effectively seal the lips around the mouthpiece, especially during forced manoeuvres such as spirometric and maximal respiratory pressure measurements [9,10]. In these cases, the conventional equipment with a tube or flanged type of mouthpiece is not adequate to evaluate respiratory muscle function. Therefore, a face mask adjusted to a portable spirometer and manometer was used to minimise air leakage in neuromuscular patients.The objective of this study was two-fold. First, possible differences in measurements between the original devices with the conventional mouthpiece and the face mask-adjusted devices were studied in healthy subjects. Secondly, a study to render new prediction equations for face mask spirometry and maximal re...