Paramyotonia congenita (Eulenburg disease) is a defect in a gene at the 17q13.1-13.3 locus, the identical locus identified in hyperkalemic periodic paralysis. ![]() Patients have difficulty when swimming in cold water or if they are dressed inadequately in cold weather. Paramyotonia is a temperature-related myotonia that is aggravated by cold and alleviated by warm external temperatures. This gene is important for the integrity of chloride channels of the sarcolemmal and T-tubular membranes. The autosomal dominant and autosomal recessive forms of myotonia congenita have been mapped to the same 7q35 locus. Patients with the recessive form (Becker disease) tend to be have more severe disease. However, specifically, missense mutations that alter the activation of the CLC-1 dimer lead to the dominantly inherited forms of the disease. Mutations may be nonsense, missense, or frameshift. Various families are described as showing either autosomal dominant (Thomsen disease) or recessive (Becker disease, not to be confused with BMD or DMD) inheritance. Muscle biopsy specimens show minimal pathologic changes, and the EMG demonstrates myotonia. The disease is clinically stable and is apparently not progressive for many years. Myotonia is prominent and can develop at age 2-3 yr, earlier than in myotonic dystrophy. ![]() Myotonia congenita (Thomsen disease), a type of channelopathy, is the most common of the nondystrophic myotonia syndromes ( Tables 627.1 to 627.4) and is characterized by weakness and generalized muscular hypertrophy so that affected children resemble bodybuilders (Herculean appearance). Muscle biopsy reveals nonspecific myopathic features, which are minimal in some cases and pronounced in others. The muscle protein perlecan, encoded by the SJS1 gene, a large heparan sulfate proteoglycan of basement membranes and cartilage, is defective in some cases of Schwartz-Jampel disease and explains both the muscular hyperexcitability and the chondrodysplasia.ĮMG reveals continuous electrical activity in muscle fibers, closely resembling or identical to myotonia. Several patients have been the products of consanguinity, suggesting autosomal recessive inheritance. Dwarfism, joint abnormalities, and blepharophimosis are present. Dysmorphic phenotypic features and the radiographic appearance of long bones are reminiscent of Morquio disease (see Chapter 107), but abnormal mucopolysaccharides are not found. Myotonic chondrodystrophy (Schwartz-Jampel disease) is a rare congenital disease characterized by generalized muscle hypertrophy and weakness. However, myotonia is not specific for this disease and occurs in several rarer conditions. Most patients with myotonia have myotonic dystrophy. Kliegman MD, in Nelson Textbook of Pediatrics, 2020 Other Myotonic Syndromes Germinal mosaicism is a real phenomenon and therefore future affected pregnancies are a possibility. This is likely to be the explanation for the rare cases of two children with the same autosomal dominant condition being born to unaffected parents. There is a slight chance that a parent of a child with an apparently new dominant mutation has gonadal mosaicism: the germ line contains two populations of cells, one with the mutation, and one with the normal gene. The recurrence risk for parents is small, but the child is at 50% risk of passing on the disease to their future children. If both parents are unaffected, and there is no family history, then the child's disease is likely to be due to a new mutation. ![]() Some patients with severe autosomal dominant conditions appear to be sporadic cases. Very rarely, a person who must carry the gene for an autosomal dominant condition fails to show any signs of the condition, the gene is said to be ‘non-penetrant’ in this individual. ![]() Unfortunately, a parent with minor signs of a dominant trait can have a severely affected child. a child may inherit the gene for autosomal dominant ectrodactyly and have severe hand anomalies, but the affected parent may show signs only on radiology. Indeed, some dominant traits are so variable in their expression that careful physical examination is needed to detect the minute signs that a parent has the gene, e.g. Each offspring of a parent with an autosomal dominant trait has a 1 in 2 chance of inheriting the condition ( Figure 7-4).Īutosomal dominant traits can exhibit variable expressivity, reduced penetrance and sex limitation. Isolated cases within a family may arise as a new mutation. Tessa Homfray, Peter A Farndon, in Twining's Textbook of Fetal Abnormalities (Third Edition), 2015 Autosomal Dominant Inheritance Including MosaicismĪ dominant trait is one that manifests in a heterozygote (only one altered copy of the gene is required) and is usually transmitted from one generation to the next (‘vertical transmission’) ( Figure 7-3).
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |