Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral, non paralytic and peripheral paralytic hypotonia are briefly discussed. Criteria which help in the differential diagnosis are emphasized. In the usual cerebral hypotonia, muscle strength is preserved but muscle tone is decreased. However, there are a few conditions in which cerebral hypotonia is severe enough to resemble paralytic hypotonia. These conditions include the Prader-Willi syndrome (first phase), the Zellweger syndrome and some cases of congenital myotonic dystrophy. In peripheral or paralytic hypotonia muscle weakness and hypotonia go hand-in-hand. A few practical diagnostic criteria are given which allow the differentiation between anterior horn cell disease, polyneuropathy, neonatal myasthenia and myopathy. Finally, essential or benign hypotonia is briefly alluded to.
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PMID:The floppy infant: a practical approach. 636 Sep 59

About 12% of children of myasthenic mothers exhibit a transitory myasthenic syndrome. Usually, these symptoms have disappeared after a few weeks. Treatment with anticholinesterase drugs is successful. The purpose of this paper is to present an infant born to a myasthenic mother, with distal arthrogryposis, severe hypotonia and respiratory distress, unresponsive to administration of pyridostigmine bromide. Eleven other cases of neonatal myasthenia with arthrogryposis are known. Five of them were stillborn or died within the first day of life. The surviving children had profound weakness and needed ventilatory assistance for a long period. The severity of these few cases contrasts with the numerous reports of benign and transitory signs of neonatal myasthenia. Passively transferred maternal acetylcholine receptor antibodies may produce illness in the newborn.
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PMID:Arthrogryposis multiplex in a newborn of a myasthenic mother--case report and literature. 826 31

For patients the author has observed, the majority of complaints following an acute pyrethroid intoxication disappeared after the end of exposure. Residuals frequently observed after more than 2 years were: (1) cerebro-organic disorders (reduced intellectual performance with 20-30% reduction of endurance during mental work, personality disorder), visual disturbances, dysacousia, tinnitus; (2) sensomotor-polyneuropathy most frequently in the lower legs; (3) vegetative nervous disorders (paroxysmal tachycardia, pollakisuria, increased heat-sensitivity, orthostatic hypotonia and reduced exercise tolerance due to circulatory disorder). Non-neurological symptoms include deficiency of cellular and humoral immune system established by laboratory findings: opportunistic infections, especially Candida-infections of the gastro-intestinal tract, relapsing infections of the urinary and respiratory tract, the latter often aggravating to respiratory obstruction. Most of the patients exhibit positive epi- or intracutantest against pyrethroids or pyrethrines, and acquainted sensitivity also to other antigens. Many of these patients exhibit pathological autoimmune diagnostical findings and developed autoimmune diseases as for instance scleroderma-like syndrome, myasthenia-like syndrome with progredient muscle atrophy, autoimmun-hemolysis and autoimmun-thrombocytopenic purpura.
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PMID:Chronic sequelae and irreversible injuries following acute pyrethroid intoxication. 1041 93

The Congenital Myasthenic Syndromes (CMS), a group of heterogeneous genetic disorders of neuromuscular transmission, are often misdiagnosed as congenital muscular dystrophy (CMD) or myopathies and present particular management problems. We present our experience of 46 children with CMS, referred to us between 1992-2007 with provisional diagnoses of congenital myopathy (22/46), CMS or limb-girdle myasthenia (9/46), central hypotonia or neurometabolic disease (5/46), myasthenia gravis (4/46), limb-girdle or congenital muscular dystrophy (4/46) and SMA (2/46). Diagnosis was often considerably delayed (up to 18y4 m), despite the early symptoms in most cases. Diagnostic clues in the neonates were feeding difficulties (29/46), hypotonia with or without limb weakness (21/46), ptosis (19/46), respiratory insufficiency (12/46), contractures (4/46) and stridor (6/46). Twenty-five children had delayed motor milestones. Fatigability developed in 43 and a variable degree of ptosis was eventually present in 40. Over the period of the study, the mainstay of EMG diagnosis evolved from repetitive nerve stimulation to stimulation single fibre EMG. The patients were studied by several different operators. 66 EMGs were performed in 40 children, 29 showed a neuromuscular junction abnormality, 7 were myopathic, 2 had possible neurogenic changes and 28 were normal or inconclusive. A repetitive CMAP was detected in only one of seven children with a COLQ mutation and neither of the two children with Slow Channel Syndrome mutations. Mutations have been identified so far in 32/46 children: 10 RAPSN, 7 COLQ, 6 CHRNE, 7 DOK7, 1 CHRNA1 and 1 CHAT. 24 of 25 muscle biopsies showed myopathic changes with fibre size variation; 14 had type-1 fibre predominance. Three cases showed small type-1 fibres resembling fibre type disproportion, and four showed core-like lesions. No specific myopathic features were associated with any of the genes. Twenty children responded to Pyridostigmine treatment alone, 11 to Pyridostigmine with either 3, 4 DAP or Ephedrine and five to Ephedrine alone. Twenty one children required acute or chronic respiratory support, with tracheostomy in 4 and nocturnal or emergency non-invasive ventilation in 9. Eight children had gastrostomy. Another 11 were underweight for height indicative of failure to thrive and required dietetic input. A high index of clinical suspicion, repeat EMG by an experienced electromyographer and, if necessary, a therapeutic trial of Pyridostigmine facilitates the diagnosis of CMS with subsequent molecular genetic confirmation. This guides rational therapy and multidisciplinary management, which may be crucial for survival, particularly in pedigrees where previous deaths have occurred in infancy.
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PMID:Congenital myasthenic syndromes in childhood: diagnostic and management challenges. 1870 67

Mutations in DOK7 are a common cause of congenital myasthenia. Treatment with ephedrine or salbutamol is effective, but diagnosis is often delayed. The aim of our study was to find early clues to the diagnosis of DOK7 congenital myasthenic syndrome. We included 23 children of 20 families. Onset of symptoms ranged from birth to age 3 years. 13 presented at birth with feeding difficulties, 11 with stridor (documented vocal cord palsy in 7), 3/11 with hypotonia/poor head control. Weakness was more pronounced proximally in all, axial in early presenting infants. Muscle biopsy showed non-specific features in 15/16, type 1 fibre predominance in 14/16, areas devoid of oxidative enzyme activity in 7/16. Muscle imaging was normal in 8/10, 2/10 showed mild non-specific changes. A diagnostic clue suggesting CMS rather than myopathy was the discrepancy between muscle imaging or histology findings compared with the degree of weakness. Repetitive nerve stimulation and stimulation single fibre electromyography were pathological in 9/17 and 13/14, respectively. In conclusion, stridor and feeding difficulties at birth or progressive weakness despite normal milestones in infancy point to the diagnosis and should lead to neurophysiological and genetic investigation. Fatigability can be absent or easily missed in the first years of life.
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PMID:DOK7 congenital myasthenic syndrome in childhood: early diagnostic clues in 23 children. 2383 Nov 58

Hypotonia in the neonatal period and early infancy is a common clinical finding. It can be caused by various heterogeneous disorders of different origin which might lead to diagnostic difficulties. Disorders of the neuromuscular junction, such as congenital myasthenic syndromes and neonatal transient myasthenia gravis are among the aetiologies. We report on a case of congenital myasthenia caused by mutation in the long cytoplasmic loop of the epsilon subunit of the acetylcholine receptor and a neonate of a myasthenic mother diagnosed with transient myasthenia gravis.
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PMID:Congenital myasthenic syndromes and transient myasthenia gravis. 2390 21

The NaV1.4 sodium channel is highly expressed in skeletal muscle, where it carries almost all of the inward Na+ current that generates the action potential, but is not present at significant levels in other tissues. Consequently, mutations of SCN4A encoding NaV1.4 produce pure skeletal muscle phenotypes that now include six allelic disorders: sodium channel myotonia, paramyotonia congenita, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, congenital myasthenia, and congenital myopathy with hypotonia. Mutation-specific alternations of NaV1.4 function explain the mechanistic basis for the diverse phenotypes and identify opportunities for strategic intervention to modify the burden of disease.
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PMID:Sodium Channelopathies of Skeletal Muscle. 2893 73

Pathogenic mutations in DPAGT1 cause a rare type of a congenital disorder of glycosylation termed DPAGT1-CDG or, alternatively, a milder version with only myasthenia known as DPAGT1-CMS. Fourteen disease-causing mutations in 28 patients from 10 families have previously been reported to cause the systemic form, DPAGT1-CDG. We here report on another 11 patients from 8 families and add 10 new mutations. Most patients have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. We also present data on three affected females that are young adults and have a somewhat milder, stable disease. Our findings expand both the molecular and clinical knowledge of previously published data but also widen the phenotypic spectrum of DPAGT1-CDG.
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PMID:DPAGT1 Deficiency with Encephalopathy (DPAGT1-CDG): Clinical and Genetic Description of 11 New Patients. 3011 11

Voltage-gated sodium channels are essential for excitability of skeletal muscle fibres and neurons. An increasing number of disabling or fatal paediatric neurological disorders linked to mutations of voltage-gated sodium channel genes are recognised. Muscle phenotypes include episodic paralysis, myotonia, neonatal hypotonia, respiratory compromise, laryngospasm or stridor, congenital myasthenia, and myopathy. Evidence suggests a possible link between sodium channel dysfunction and sudden infant death. Increasingly recognised phenotypes of brain sodium channelopathies include several epilepsy disorders and complex encephalopathies. Together, these early-onset muscle and brain phenotypes have a substantial morbidity and a considerable mortality. Important advances in understanding the pathophysiological mechanisms underlying these channelopathies have helped to identify effective targeted therapies. The availability of effective treatments underlines the importance of increasing clinical awareness and the need to achieve a precise genetic diagnosis. In this Review, we describe the expanded range of phenotypes of muscle and brain sodium channelopathies and the underlying knowledge regarding mechanisms of sodium channel dysfunction. We also outline a diagnostic approach and review the available treatment options.
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PMID:Muscle and brain sodium channelopathies: genetic causes, clinical phenotypes, and management approaches. 3214 33