Hormonal variations during the menstrual cycle (MC) may influence trainability of strength. We investigated the effects of a follicular phase-based strength training (FT) on muscle strength, muscle volume and microscopic parameters, comparing it to a luteal phase-based training (LT). Eumenorrheic women without oral contraception (OC) (N = 20, age: 25.9 ± 4.5 yr, height: 164.2 ± 5.5 cm, weight: 60.6 ± 7.8 kg) completed strength training on a leg press for three MC, and 9 of them participated in muscle biopsies. One leg had eight training sessions in the follicular phases (FP) and only two sessions in the luteal phases (LP) for follicular phase-based training (FT), while the other leg had eight training sessions in LP and only two sessions in FP for luteal phase-based training (LT). Estradiol (E2), progesterone (P4), total testosterone (T), free testosterone (free T) and DHEA-s were analysed once during FP (around day 11) and once during LP (around day 25). Maximum isometric force (F_max), muscle diameter (Mdm), muscle fibre composition (No), fibre diameter (Fdm) and cell nuclei-to-fibre ratio (N/F) were analysed before and after the training intervention. T and free T were higher in FP compared to LP prior to the training intervention (P < 0.05). The increase in F_max after FT was higher compared to LT (P <0.05). FT also showed a higher increase in Mdm than LT (P < 0.05). Moreover, we found significant increases in Fdm of fibre type ΙΙ and in N/F only after FT; however, there was no significant difference from LT. With regard to change in fibre composition, no differences were observed between FT and LT. FT showed a higher gain in muscle strength and muscle diameter than LT. As a result, we recommend that eumenorrheic females without OC should base the periodization of their strength training on their individual MC.

Mutations in the filamin C gene (FLNC) cause a myofibrillar myopathy (MFM), morphologically characterized by focal myofibrillar destruction and abnormal accumulation of several proteins within skeletal muscle fibres. We studied 31 patients from four German families to evaluate the phenotype of filaminopathy. All patients harboured the same p.W2710X mutation in FLNC. Haplotype analysis suggested a founder mutation in these German filaminopathy families. The mean age at onset of clinical symptoms was 44 +/− 6 years (range, 24–57 years). Slowly progressive muscle weakness was mostly pronounced proximally, initially affecting the lower extremities and involving the upper extremities in the course of disease progression, similar to the distribution of weakness seen in limb-girdle muscular dystrophies (LGMD). Patients frequently developed respiratory muscle weakness. About one-third of the patients showed cardiac abnormalities comprising conduction blocks, tachycardia, diastolic dysfunction and left ventricular hypertrophy indicating a cardiac involvement in filaminopathy. Serum creatine kinase levels varied from normal up to 10-fold of the upper limit. Magnetic resonance imaging studies showed a rather homogenous pattern of muscle involvement in the lower extremities differing from that in other types of MFM. Myopathological features included perturbation of myofibrillar alignment, accumulation of granulofilamentous material similar to that seen in primary desminopathies and abnormal intracellular protein deposits typical of MFM. Decreased activities of oxidative enzymes and fibre hypertrophy seem to be early features, whereas dystrophic changes were present in advanced stages of filaminopathy. Rimmed vacuoles were detected in only a few cases. The intracellular aggregates were composed of a variety of proteins including filamin C, desmin, myotilin, Xin, dystrophin and sarcoglycans. Therapy is so far limited to symptomatic treatment. The German filaminopathy cohort, the largest group of patients studied so far, shares phenotypic features with LGMD and presents with characteristic histopathological findings of MFM.

The term filaminopathy was introduced after a truncating mutation in the dimerization domain of filamin C (FLNc) was shown to be responsible for a devastating muscle disease. Subsequently, the same mutation was found in patients from diverse ethnical origins, indicating that this specific alteration is a mutational hot spot. Patients initially present with proximal muscle weakness, while distal and respiratory muscles become affected with disease progression. Muscle biopsies of these patients show typical signs of myofibrillar myopathy, including disintegration of myofibrils and aggregation of several proteins into distinct intracellular deposits. Highly similar phenotypes were observed in patients with other mutations in Ig-like domains of FLNc that result in expression of a noxious protein. Biochemical and biophysical studies showed that the mutated domains acquire an abnormal structure causing decreased stability and eventually becoming a seed for abnormal aggregation with other proteins. The disease usually presents only after the fourth decade of life possibly as a result of ageing-related impairments in the machinery that is responsible for disposal of damaged proteins. This is confirmed by mutations in components of this machinery that cause a highly similar phenotype. Transfection studies of cultured muscle cells reflect the events observed in patient muscles and, therefore, may provide a helpful model for testing future dedicated therapeutic strategies. More recently, FLNC mutations were also found in families with a distal myopathy phenotype, caused either by mutations in the actin-binding domain of FLNc that result in increased actin-binding and non-specific myopathic abnormalities without myofibrillar myopathy pathology, or a nonsense mutation in the rod domain that leads to RNA instability, haploinsufficiency with decreased expression levels of FLNc in the muscle fibers and myofibrillar abnormalities, but not to the formation of desmin-positive protein aggregates required for the diagnosis of myofibrillar myopathy.

MCARDLE DISEASE is a rare autosomal recessive metabolic myopathy caused by a defect of the muscle-specific isozyme of glycogen phosphorylase that leads to a blockade of adenosine triphosphate (ATP) formation from glycogen in skeletal muscle. The defect in the glycogen breakdown pathway leads to deprivation of an important energy source, particularly during the early stages of exercise when the availability of fatty acids for oxidation is limited. Typically, patients with McArdle disease have exercise intolerance with premature fatigue, exercise-induced muscle pain in working muscles, and recurrent myoglobinuria, which usually start in childhood. Treatments for McArdle disease have been unsatisfactory.¹

Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B).

MCARDLE DISEASE (glycogenosis type V) is one of the most common metabolic myopathies and is caused by genetic defects of the muscle-specific isozyme of glycogen phosphorylase, which block adenosine triphosphate (ATP) formation from glycogen in skeletal muscle. Typically, patients with McArdle disease have exercise intolerance, with premature muscle fatigue, exercise-induced muscle pain in working muscles, and recurrent myoglobinuria. Treatment of McArdle disease has been unsatisfactory to date and therefore remains an important clinical challenge.