Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers.

Facioscapulohumeral muscular dystrophy (FSHD) is associated with a decreased number of D4Z4 repeats on chromosome 4q35. Diagnostic difficulties arise from atypical clinical presentations and from an overlap in D4Z4 numbers between controls and FSHD individuals. Thus, a molecular genetic test result with a borderline D4Z4 number has its limitations for the clinician wanting to differentiate between the diagnosis of FSHD and a myopathy presenting with FSHD-like symptoms.To investigate this problem in more detail we conducted a systematic study of 39 unrelated FSHD patients with borderline D4Z4 repeat numbers and 102 healthy controls. Our aim was threefold: [1] to define the molecular diagnostic cut-off point between FSHD cases and the control population, [2] to describe the myopathic spectrum in patients with borderline D4Z4 repeat numbers and [3] to look for correlations between D4Z4 number and clinical severity. The results indicate that there is no definite D4Z4 diagnostic cut-off point separating FSHD, FSHD-like myopathies and controls. A broad myopathic spectrum with four phenotypes (typical FSHD, facial-sparing FSHD, FSHD with atypical features, non-FSHD muscle disease) was found in the borderline region. The expected correlation of D4Z4 repeat number and clinical severity was not found. Therefore the molecular test is of limited help to differentiate FSHD from FSHDlike muscle disorders when the D4Z4 number is n = >or= 8.

Longitudinal effects of noninvasive positive-pressure ventilation in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate the duration of benefit on symptoms, quality of life, and survival derived from the use of noninvasive positive-pressure ventilation by patients with amyotrophic lateral sclerosis. DESIGN: In this prospective, cohort study, 30 of 36 consecutively referred symptomatic patients tolerated nightly noninvasive positive-pressure ventilation and undertook pulmonary function testing and 12 symptom and quality-of-life instruments concerning sleep quality, daytime sleepiness, physical fatigue, mental fatigue, and depression that were administered during a 10-mo period. RESULTS: With treatment, there was a significant improvement in the majority of patients in sleep quality, daytime sleepiness, physical fatigue, and depression; however, significant improvements lasted for up to 10 mo only in sleep quality. Partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, and oxyhemoglobin saturation remained stable or even improved for up to 7 mo during use of part-time noninvasive positive-pressure ventilation. A total of 14 patients had survival prolonged by continuous dependence on noninvasive positive-pressure ventilation. CONCLUSIONS: Noninvasive positive-pressure ventilation provides a long-lasting benefit on symptoms and quality of life indicators for amyotrophic lateral sclerosis patients and should be offered to all patients with symptoms of sleep disordered breathing or inspiratory muscle dysfunction. It can also prolong tracheostomy-free survival.