Myotonic

The only one of these conditions which causes progressive and degenerative disease of muscle is myotonic dystrophy. Inheritance is autosomal dominant, but expression is very variable. The condition also illustrates the phenomenon of... 

Myotonic dystrophy AD 19q13 Myotonin protein kinase Muscle chloride channel... 

The histopathological features of muscle samples from patients with myotonic dystrophy are not particularly distinctive. Early changes appear to be a selective atrophy of type 1 fibers, and hypertrophy of type 2 fibers, but the biochemical and/or physiological basis of these possibly related phenomena is not known. The incidence of degenerating fibers increases with age, although the presence of internally nucleated muscle fibers in early stages of the disease suggests that the muscle retains... 

Congenital myotonic dystrophy is a relatively rare condition in which myotonia (defined electrically) is mostly absent in the affected newborn infant, but becomes apparent in the older infant. Histopathology shows a consistent feature of arrested development and maturation of muscle fibers, but there is, currently, no adequate explanation for this phenomenon. Patients with congenital myotonic dystrophy rarely survive without aggressive ventilatory support, and survivors, without exception, are severely multiply handicapped. 

There is no single underlying cause for the myotonia seen in the muscles of myotonic patients. The typical myotonic response is a train of action potentials generated in a muscle fiber in response to a single stimulus. Experimental work has shown that such a response can be generated in normal muscle fibers in which chloride conductance is suppressed, and this may be the cause of the myotonia of Thomsen s disease (see Barchi, 1988 for examples). It is almost certainly not the cause of myotonia in myotonic dystrophy in which there is an associated fall in... 

Thyrotoxicosis Pheochromocytoma Myotonic dystrophy Trigeminal neuralgia... 

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

Blindness (several forms) Deafness (several forms) Marfan syndrome Achondroplasia Neurofibromatosis Myotonic dystrophy Tuberous sclerosis All others... 

The pumiliotoxins, alio- and homopumiliotoxins, are alkaloids isolated from the skin of amphibians, such as neotropical frogs of the Dendrobatidae family, and are believed to serve as a chemical defence against predators. These natural products have interesting pharmacological properties, including myotonic and cardiotonic activities. 

Enteric Myopathies. The familial types include the dominant type 1 [150], the recessive type 2 with ophthalmoplegia [151] and the recessive type 3 [116]. The sporadic types include muscular dystrophies [152] including myotonic dystrophy [153] and Duchenne s dystrophy. Dysmotility has been associated with all these diseases. 

Nowak TV, Anuras S, Brown BP, Ionasescu V, Green JB Small intestinal motility in myotonic dystrophy patients. Gastroenterology 1984 86 808-813. 

Serum CK is consistently increased in all forms of AMD. Forearm ischemic exercise causes a normal rise of venous lactate concentration in patients with childhood or adult AMD. The electrocardiogram (ECG) is altered in Pompe s disease, with a short P-R interval, giant QRS complexes and left ventricular or biventricular hypertrophy, but is usually normal in the later-onset forms. The EMG shows myopathic features and fibrillation potentials, bizarre high-frequency discharges and myotonic discharges. 

There is no glycemic response to glucagon or epinephrine (Fig. 42-1), whereas a galactose load causes a normal glycemic response. Forearm ischemic exercise produces a blunted venous lactate rise or no response. Serum CK activity is variably, often markedly, increased. The ECG shows left ventricular or biventricular hypertrophy in most patients, and the EMG may show myopathic features alone or associated with fibrillations, positive sharp waves and myotonic discharges. This mixed EMG pattern in patients with weakness and distal wasting often reinforces... 

Ribonuclear inclusions are responsible for the multiple manifestations of myotonic dystrophy 722... 

Steinmeyer, K., Klocke, R., Ortland, C. et al. Inactivation of muscle chloride channel by transposon insertion in myotonic mice. Nature 354 304—306,1991. 

Another class of these amphibian alkaloids, the pumiliotoxins, contain an alkylidene side chain on C-6 of the indolizidine ring (Table 2). Due to their myotonic and cardiotonic activity, and challenging structure, they also have been the object of synthetic interest. A review points out the state of the art at the beginning of the decade <1996CRV505>. 

The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. 

Myotonic Dystrophy A condition presenting muscle weakness and wasting which may be progressive. [NIH]... 

Trinucleotide Repeat Expansion DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats, [nih]... 

Figure 1-7-10. EeoRI RFLP Analysis of a Family With Myotonic Dystrophy...

The gene involved in myotonic dystrophy encodes a protein kinase whose function is still uncharacterized, The disease is characterized by progressive muscle deterioration, cardiac amhythmia, frontal baldness, cataracts, and teaicular atrophy. Because the disease shows anticipation, symptoms range ftom mild to a severe neonatal condition. 

Pain, muscular weakness, cramps and ease of fatigue are the most usual symptoms of muscular disease. In most cases, it is diseases of the vascular or nervous system or problems with the processes providing energy within the muscle that are responsible for clinical problems with muscles. Other clinical problems include the muscular dystrophies, myotonic disorders, inflammatory myopathies and disorders of neuromuscular transmission (see Walton, 1996). The best known is Duchenne muscular dystrophy. 

Gareiss, P. C. Sobczak, K. McNaughton, B. R. Thornton, C. A. Miller, B. L. Dynamic combinatorial selection of small molecules capable of inhibiting the (CUG) repeat RNA-MBNLl interaction in vitro Discovery of lead compounds targeting myotonic dystrophy (DM1). J. Am. Chem. Soc., 2008, 130, 16524-16261. 

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