Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, is a clinically and genetically heterogeneous neuromuscular disorder. DM is characterized by autosomal dominant inheritance, muscular dystrophy, myotonia, and multisystem involvement. Type 1 DM (DM1) is caused by a (CTG)(n) expansion in the 3' untranslated region of DMPK in 19q13.3. Multiple families, predominantly of German descent and with clinically variable presentation that included proximal myotonic myopathy (PROMM) and type 2 DM (DM2) but without the DM1 mutation, showed linkage to the 3q21 region and were recently shown to segregate a (CCTG)(n) expansion mutation in intron 1 of ZNF9. Here, we present linkage to 3q21 and mutational confirmation in 17 kindreds of European origin with PROMM and proximal myotonic dystrophy, from geographically distinct populations. All patients have the DM2 (CCTG)(n) expansion. To study the evolution of this mutation, we constructed a comprehensive physical map of the DM2 region around ZNF9. High-resolution haplotype analysis of disease chromosomes with five microsatellite and 22 single-nucleotide polymorphism markers around the DM2 mutation identified extensive linkage disequilibrium and a single shared haplotype of at least 132 kb among patients from the different populations. With the exception of the (CCTG)(n) expansion, the available markers indicate that the DM2 haplotype is identical to the most common haplotype in normal individuals. This situation is reminiscent of that seen in DM1. Taken together, these data suggest a single founding mutation in DM2 patients of European origin. We estimate the age of the founding haplotype and of the DM2 (CCTG) expansion mutation to be approximately 200-540 generations.

Complementary and alternative medicine (CAM) is increasingly common in the treatment of primary headache disorders despite lack of evidence for efficacy in most modalities. A systematic questionnaire-based survey of CAM therapy was conducted in 432 patients who attended seven tertiary headache out-patient clinics in Germany and Austria. Use of CAM was reported by the majority (81.7%) of patients. Most frequently used CAM treatments were acupuncture (58.3%), massage (46.1%) and relaxation techniques (42.4%). Use was motivated by 'to leave nothing undone' (63.7%) and 'to be active against the disease' (55.6%). Compared with non-users, CAM users were of higher age, showed a longer duration of disease, a higher percentage of chronification, less intensity of headache, were more satisfied with conventional prophylaxis and showed greater willingness to gather information about headaches. There were no differences with respect to gender, headache diagnoses, headache-specific disability, education, income, religious attitudes or satisfaction with conventional attack therapy. A higher number of headache days, longer duration of headache treatment, higher personal costs, and use of CAM for other diseases predicted a higher number of used CAM treatments. This study confirms that CAM is widely used among primary headache patients, mostly in combination with standard care.

uscle carnitine palmitoyltransferase (CPT) II deficiency is an autosomal recessive disorder of fatty acid oxidation characterized by attacks of myalgia and myoglobinuria. This review summarizes the clinical features of this disease, analyzing data of 28 patients with biochemically and genetically confirmed CPT II deficiency. The review shows that exercise-induced myalgia is the most frequent symptom, whereas myoglobinuria, known as the clinical hallmark, is missing in 21% of the patients. Typically, myalgia starts in childhood, whereas attacks with myoglobinuria mostly emerge in adolescence or early adulthood. However, there are also patients with only myalgia, patients with attacks triggered by factors other than exercise, and patients with late-onset disease. Molecular or biochemical analysis is necessary for diagnosis, since no myopathologic hallmark exists. For screening patients, analysis of not only the common S113L mutation but also the P50H and Q413fs-F448L mutations is recommended. The phenotype of muscle CPT II deficiency might be influenced by the underlying mutation, and patients with a truncating mutation on 1 allele might be affected more severely.

The authors investigated 32 patients with the muscle form of CPT II deficiency. Total carnitine palmitoyltransferase enzyme system (CPT) activity was normal but abnormally inhibited by malonyl-CoA, palmitoyl-CoA, and the detergents Triton X and Tween 20. Mutation analysis identified three described mutations (S113L, P50H, and F448L) and two novel mutations (M214T and Y479F). Using modeling techniques, a structure could be identified anchoring the protein in the membrane. Only one of the five mutations (Y479F) is located within this region.

The authors performed neuropsychological testing in 21 patients with myotonic dystrophy type 1 (DM1) and 21 with type 2 (DM2) and healthy controls. They detected no general cognitive deficit in either DM1 or DM2, but compared to controls, both groups of patients were inferior in tests of prefrontal functioning. Patient groups did not differ in any measure. Mood status was not related to neuropsychological performance. This is consistent with findings of executive dysfunction in both DM1 and DM2.