No abstract

Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer. The gene involved has been localized to chromosome 10q22-23. Recently, the tumour suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual-specificity phosphatase, was cloned from that region and three mutations were detected in patients with Cowden disease. We confirmed that the PTEN/MMAC1 gene is indeed the gene for Cowden disease by a refined localization of the gene to the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene and, by mutation analysis in eight unrelated familial and 11 sporadic patients with Cowden disease. Eight different mutations were detected in various regions of the PTEN/MMAC1 gene. One mutation was detected twice. All detected changes in the gene can be predicted to have a very deleterious effect on the putative protein. Five of the nine patients have a mutation in exon 5 coding for the putative active site and flanking amino acids. Evaluation of the clinical data of the patients in which a mutation could be detected gives no clear indications for a correlation between the genotype and phenotype. In 10 patients no mutation could be detected so far. In support of the linkage data, no evidence has emerged from the phenotype of these patients suggestive for genetic heterogeneity.

No abstract

Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.

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.

In some families with early-onset autosomal dominant hearing loss, the responsible gene is on chromosome 1p.

Two types of myoadenylate deaminase (MAD) deficiency have been described, primary or inherited, and secondary or acquired MAD deficiency. In this study, we investigated whether secondary MAD deficiency is indeed acquired or merely coincidental. We demonstrated the same underlying molecular defect, a C34T transition, in both types of deficiency. Furthermore, the same frequency of the mutant MAD allele was found in the general population as in patients with neuromuscular complaints. We therefore conclude that in the Dutch population, secondary MAD deficiency is merely a "coincidental" finding, and that MAD deficiency is a harmless genetic variant.

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...