Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results are presented from the first year of our clinic in Edinburgh. These were included in the setting up of a computerized Register of Ascertainment and Prevention of Inherited Disease ('RAPID') in the Department of Human Genetics. A total of 45 relatives who had greater than 10% risk were ascertained from fifteen families with hereditary diseases; 24 relatives had 10% risk of retinitis pigmentosa. The pupils at the Royal Blind School, Edinburgh, were surveyed and it was found that 40% of the 100 pupils had definitely inherited severe eye disease. Only 31% , had definitely non-genetic disease, for which reassuring counseling can be given. In 29% we could not be sure. From those with hereditary disease we ascertained 51 relatives at greater than 10% risk. Any patient with a fairly symmetrical 'quiet' eye disease, especially if congenital, should be suspected of having an hereditary disease--presumably due to a recessive gene, even if the parents are not consanguineous, but possibly due to a mutation which could prove dominant; a search of the literature in such cases is useful. Although patients with a 'recessive' disease can be reassured that the (extra) risk to their children is small, it is worth warning them that in their families a consanguineous marriage is more liable than usual to produce affected children. A case of oculo-pharyngeal muscular dystrophy was seen and two cases of Leber's congenital amaurosis: the commonest diagnosis was retinitis pigmentosa, and there were several cases of Marfan's syndrome. The Royal Blind School takes both boys and girls and one couple have recently married, the male with X-linked retinitis pigmentosa and the female with dominantly inherited retinoblastoma.
 ...
PMID:An ophthalmic genetics clinic. 106 40

Advances in molecular genetics are leading to changes in practice that have a direct impact on the obstetrician and gynecologist. New techniques of prenatal screening, diagnosis, and potentially therapy are rapidly evolving. Recent developments in cystic fibrosis, preimplantation genetics, fragile X syndrome, neurofibromatosis, muscular dystrophy, and Marfan syndrome are discussed.
 ...
PMID:Cystic fibrosis, genetics, and DNA technology. 191 55

Snoring and obstructive sleep apnea are a frequent problem not only in adults, but also in children and adolescents, as can be seen from current epidemiological data. The epidemiology, etiology, diagnosis, and management of obstructive sleep apnea syndrome (OSAS) in adults have been adequately established on the basis of evidential data. As a result of this, both physicians and the public are increasingly aware of OSAS in adults. Although there are numerous parallels between pediatric and adult OSAS, the situation in children differs that in adults. There is a greater variety of symptoms in children with OSAS, diagnosis is often more difficult with serious consequences for growth and development of children. Treatment of OSAS in children is also different from that of the adult patient. There are many possible causes for the development of obstructive sleep apnea in children. These include hypertrophy of the tonsils and syndromes such as Down syndrome, Pickwickian syndrome, Prader-Willi syndrome or Marfan syndrome. OSAS can, however, also be the result of obesity, midfacial dysplasia, retro- or micrognathia, allergic rhinitis or muscular dystrophy. Epidemiological data presented in the literature concerning the incidence of OSAS in children is extremely varied. This wide range is probably due to the fact that snoring may be misdiagnosed as OSAS. The diagnosis of OSAS in children may only be made by considering clinical history (such as rate of growth, tendency to fall asleep during the day, sleep disturbances, susceptibility to infection, etc.), polysomnography (if possible during several nights) and accompanying instrumental diagnosis including cephalometry or laryngoscopy. One of the problems of polysomnography in childhood is that performance and interpretation of the results have not yet been standardized or evaluated for different age groups. Treatment depends on the cause of OSAS and require multidisciplinary management involving the pediatrician, pediatric or adolescent psychiatrist, ear, nose, and throat specialist, maxillofacial surgeons, and neurosurgeons. Adenotonsillectomy (ATE) is the therapy generally chosen if the child has adenoidal vegetations and/or tonsillar hypertrophy. Corrective surgery is possible for rare malformation syndromes. Nocturnal masks for continuous positive airway nasal pressure or procedures for mask respiration are effective in children, but are only used in exceptional cases, such as when ATE is contraindicated or when symptoms of OSAS remain after surgery. The success of pharmacological treatment of OSAS in children has not been evaluated in controlled clinical trials.
 ...
PMID:Obstructive sleep apnea syndrome in children: a state-of-the-art review. 1518 12

Marfan syndrome (MFS) is an inherited disorder of connective tissue due to mutations in FBN1 (90%) and TGFBR1 and TGFBR2 (5 to 10%) genes. Clinical and differential diagnosis is difficult because of the inter- and intrafamiliar marked heterogeneity and the variable onset age of clinical manifestations. Among the disorders, in differential diagnosis, thoracic aortic aneurysm (TAA) and Ullrich scleroatonic muscular dystrophy (UCMD) are reported. We evaluate the possibility of utilizing autofluorescence (AF) analysis as a diagnostic tool in the clinical and/or differential diagnosis of MFS and related disorders and in the investigation of the molecular mechanisms involved. Both multispectral imaging autofluorescence microscopy (MIAM) and autofluorescence microspectroscopy (AMS) have been used to characterize AF emission of fibroblasts from patients affected by inherited connective tissue disorders. Our preliminary results show significant differences in AF emission between normal and pathological fibroblasts, suggesting possible improvement in diagnostics of connective tissue disorders by AF analysis.
 ...
PMID:Fibroblast autofluorescence in connective tissue disorders: a future tool for clinical and differential diagnosis? 1902 5

Congenital and adult-onset inherited myopathies represent a wide spectrum of syndromes. Classification is based upon clinical features and biochemical and genetic defects. Joint hypermobility is one of the distinctive clinical features that has often been underrecognized so far. We therefore present an overview of myopathies associated with joint hypermobility: Ullrich congenital muscular dystrophy, Bethlem myopathy, congenital muscular dystrophy with joint hyperlaxity, multi-minicore disease, central core disease, and limb girdle muscular dystrophy 2E with joint hyperlaxity and contractures. We shortly discuss a second group of disorders characterised by both muscular features and joint hypermobility: the inherited disorders of connective tissue Ehlers-Danlos syndrome and Marfan syndrome. Furthermore, we will briefly discuss the extent and pattern of joint hypermobility in these myopathies and connective tissue disorders and propose two grading scales commonly used to score the severity of joint hypermobility. We will conclude focusing on the various molecules involved in these disorders and on their role and interactions in muscle and tendon, with a view to further elucidate the pathophysiology of combined hypermobility and myopathy. Hopefully, this review will contribute to enhanced recognition of joint hypermobility and thus be of aid in differential diagnosis.
 ...
PMID:Joint hypermobility as a distinctive feature in the differential diagnosis of myopathies. 1922 53

TGF-beta regulates many aspects of cellular performance relevant to tissue morphogenesis and homeostasis. Postnatal perturbation of TGF-beta signaling contributes to the pathogenesis of many disease states, as recently exemplified through the study of Marfan syndrome (MFS), including aortic aneurysm and skeletal muscle myopathy. Heterogeneity in the regulation and consequences of TGF-beta signaling, amplified in the context of disease, has engendered confusion and controversy regarding its utility as a therapeutic target. Three studies recently published in the JCI, including one in this issue, underscore the complexity of this subject. Heydemann and colleagues implicate dimorphic variation in latent TGF-beta-binding protein 4 (LTBP4), a regulator of TGF-beta bioavailability and activation, as a modifier of muscular dystrophy in gamma-sarcoglycan-deficient mice. In contrast to experience with ascending aortic aneurysm in MFS, Wang and colleagues show that systemic abrogation of TGF-beta signaling worsens (rather than attenuates) Ang II-induced abdominal aortic aneurysm progression in mice. Tieu and colleagues define alterations in the regulation of vascular inflammation in the pathogenesis of Ang II-induced aneurysm and dissection in mice, which may help shed some light on this apparent paradox.
 ...
PMID:TGF-beta in the pathogenesis and prevention of disease: a matter of aneurysmic proportions. 2010 Oct 93

Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background) are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that fibrillin-2 can sequester BMP complexes in a latent state.
...
PMID:Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice. 2611 82