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)

We report the case of a female child presented at birth with hypotonia, growth retardation and respiratory distress. Chromosome study from peripheral blood showed a 46,XX,del(5)(p14pter) karyotype. Parental chromosome studies revealed that the mother carried an apparently balanced paracentric inversion of long arms of one chromosome 5, giving the karyotype 46,XX,inv(5)(q12q32), whereas paternal karyotype was normal. The maternal abnormality was confirmed by fluorescence in situ hybridization (FISH) and was not present in the daughter's metaphases. Microsatellite analysis in the proposita and her parents permitted us to conclude that the deleted chromosome 5 was paternal in origin, as usually described. Therefore, as might have been expected, maternal paracentric inversion of chromosome 5q and "cri-du-chat syndrome" presented by the daughter were not related.
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PMID:"Cri-du-chat" syndrome in a patient born to a mother with a paracentric inversion of chromosome 5q. 1465 87

The congenital myasthenic syndromes (CMS) constitute a group of genetic disorders, which affect neuromuscular transmission, presenting usually within the first years of life and with a clinical spectrum ranging from mild muscle weakness to severe disability with life-threatening episodes. We present clinical and neurophysiological data of 11 patients (four males, seven females) with CMS diagnosed during the last 5 years. Eight of the 11 patients presented immediately after birth and the remainder by 10 months of age; eight patients had contractures at birth and seven of them required assisted ventilation either immediately in the neonatal period, or at some point afterwards due to respiratory distress or recurrent apnoeas. Neurological signs at presentation were: in nine patients profound hypotonia, in five absent tendon reflexes, in seven ptosis and in eight bulbar signs. In six patients an edrophonium test was performed: only three of them had a positive response; however, eight out of 11 patients responded at least partially at some point in their illness to pyridostigmine. Diagnosis of CMS was confirmed either by demonstration of a decrement after repetitive nerve stimulation or by increased instability and jitter after stimulated single fibre EMG. In five patients, there was a positive family history with death of at least one previous sibling with an undiagnosed neuromuscular disorder. As regards final outcome, five patients died at ages ranging from 1 to 17 months, two patients are still ventilator-dependent at 3 and 5 months of life, respectively, and four patients still survive with either a mild or a moderate motor delay (follow-up range 8-38 months). None of the clinical or neurophysiological characteristics were correlated with outcome (Fisher's exact test). We conclude that a significant number of CMS patients may present in the neonatal period with a variable clinical expression and usually with a poor prognosis. The recognition of specific clinical constellations combined with a search for aetiology at a molecular level will enable the further characterisation of subgroups of CMS.
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PMID:Clinical and neurophysiological characteristics of congenital myasthenic syndromes presenting in early infancy. 1472 15

Rare cases of suspected spinal muscular atrophy (SMA) have been found to have cytochrome c oxidase (COX) deficiency. To date, four cases with SMA features have been reported in children with mutations in the synthesis of cytochrome oxidase 2 (SCO2) gene. We report a male neonate who was born hypotonic, with persistent lactic acidosis, spontaneous activity with EMG testing, development of respiratory distress in the first few hours of life, and died at 30 days of age with progressive cardiomyopathy. Testing for survival motor neurone (smn) and NAIP deletions were negative and a skeletal muscle biopsy showed neurogenic features with severe reductions of COX enzymatic and histochemical staining intensity. Post-mortem muscle, heart, and liver biopsies showed severe, moderate, and mild reductions in COX activity, respectively, with parallel findings in the protein content for the mitochondrial DNA (COII) and nuclear DNA (COIV) encoded subunits. DNA sequencing of exon 2 of the SCO2 gene revealed compound heterozygosity with mutations at G1541A (common mutation, E140K) and also at a novel site in the copper binding region (G1521A in the current case (converting a highly conserved cysteine to tyrosine [corrected] (C133Y) [corrected]); mother heterozygous for G1521A; and father heterozygous for G1541A). This case provides strong support that SCO2 mutations can result in neonatal hypotonia with an SMA 1 phenotype. SCO2 mutations should be screened in suspected SMA cases with normal smn mutation analysis and any one of; cardiomyopathy, lactic acidosis, or COX deficiency in muscle.
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PMID:Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type I phenotype. 1499 43

This article presents a literature review on the treatment with new antidepressants during pregnancy and lactation, focusing on possible unwanted effects to the fetus and infant. Most data is available for the selective serotonin reuptake inhibitors, and particularly for fluoxetine. Some information exists for venlafaxine, whereas no published data was found for other new antidepressants such as reboxetine and mirtazapine. In general, treatment with new antidepressants during the first trimester in pregnancy has not been associated with an increased risk for congenital malformations. In contrast, symptoms such as irritability, respiratory distress and muscular hypotonia have been reported in newborns after third trimester exposure. The excretion of new antidepressants in breast milk seems in most cases to be negligible. However, suspected adverse effects have been reported in a few infants. In conclusion, existing data seems to indicate that the positive effects of maternal drug treatment and of lactation to the infant generally outweigh the risks of possible pharmacological effects. Nevertheless, before a new antidepressant is prescribed to a pregnant or lactating woman, an individual risk/benefit-assessment should always be carried out.
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PMID:[New antidepressive agents during pregnancy and lactation. Drug concentration should be monitored and the lowest possible dose administered]. 1510 Dec 42

We describe 6 unrelated patients affected by infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1) with prolonged survival upon mechanical ventilation (4.5-11 years), which has not been reported before. Biallelic mutations in the IGHMBP2 gene proved the diagnosis of SMARD1 in all patients. Disease onset was in the first 2 months in the described patients, starting with generalised hypotonia, failure to thrive, and early breathing difficulties. Diaphragmatic palsy was diagnosed and permanent ventilation was initiated 2-8 months after onset. Within months a more distal muscular atrophy became evident associated with joint contractures (talipes), hand drops, and fatty finger pads. Motor development remained minimal, loss of function was observed within the first year after which no further progression was recorded. Voiding dysfunction with reflux nephropathy was observed in 3 patients and has not been reported before. Further evidence of autonomic nerve dysfunction resulting in cardiac arrhythmia, hypertension, and excessive sweating was given in 2 patients. Investigative results were largely compatible with those obtained in classic SMA. However, neurogenic atrophy muscle was more pronounced in distal muscles, if examined, and there was evidence of peripheral nerve involvement at least in some patients.
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PMID:Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). 1524

3-Hydroxy-3-methylglutaric aciduria (OMIM 246450) is an autosomal recessive inborn error of the final step of leucine catabolic and ketogenic pathways, caused by deficiency of the enzyme 3-hydroxy-3-methylglutaryl CoA lyase (HL, HMGCL, EC 4.1.3.4). Clinically, deficiency of the enzyme results in metabolic acidosis, hyperammonemia, and infantile hypoketotic hypoglycaemia usually presenting during the first year of life with vomiting, lethargy, hypotonia, and sometimes with respiratory distress and coma. HL deficiency is relatively common in Arabic populations but seems to be rare in Europe. Our recent experience suggests that HL deficiency is the most frequent organic aciduria in the Portuguese population. We herein report on the molecular study of the HMGCL gene in 11 cases originated from the Northern area of Portugal. We detected the E37X (c.109G > T) mutation, in 84.1% of the alleles, one allele carried the V168fs(-2) (504_505delCT) and other allele the novel D204N (c.610G > A) mutation. The mutation of the last allele remained unidentified. The relatively high frequency of the "common" HMGCL Portuguese mutation makes useful the development of a rapid and specific molecular confirmation of new cases with HL deficiency in our country.
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PMID:The E37X is a common HMGCL mutation in Portuguese patients with 3-hydroxy-3-methylglutaric CoA lyase deficiency. 1530 32

We report the cases of 3 children with postsynaptic congenital myasthenic syndrome with acetylcholine receptor deficiency due to rapsyn deficiency. Symptoms began at the neonatal period with hypotonia, arthrogryposis, bulbar symptoms, and respiratory distress. Two of the 3 children needed tracheostomy and gastrostomy. Electromyograms showed a decremental response to repetitive stimulation. Muscle biopsies were normal or showed type I fiber preponderance. Genetic studies identified mutations in the rapsyn gene (RAPSN). The 3 patients were heterozygous for N88 K and a second mutation (either Y86X, 1083_1084 dupCT or IVS4-2 A > G). The patients responded favorably to anticholinesterase treatment, with a clear improvement of clinical symptoms, especially the bulbar symptoms of apneas and swallowing disturbances. This paper underlines the importance of anticholinesterase medication in patients with congenital myasthenic syndrome due to rapsyn deficiency.
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PMID:Congenital myasthenic syndrome due to rapsyn deficiency: three cases with arthrogryposis and bulbar symptoms. 1532 66

The clinical features of Prader-Willi Syndrome (PWS) in the neonate are marked by hypotonia, absence of crying, and feeding difficulties, but the clinical nature of PWS in utero remains unclear. We report a case of PWS with fetal immobility and distal arthrogryposis in a girl admitted the first day of life to the neonatal intensive care unit for severe hypotonia and respiratory distress.
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PMID:Distal arthrogryposis and neonatal hypotonia: an unusual presentation of Prader-Willi syndrome (PWS). 1551 Jan 4

I report the case of an infant girl who was exposed to lithium during gestation and her follow-up at the age of 1 year. She presented with transient neurodevelopmental deficits including lethargy, hypotonia, and poor oral feeding ability in the neonatal period. She required supportive treatment and made gradual improvement in neurologic functioning. On examination at the age of 1 year, physical findings and psychomotor development were normal. The English literature from 1978 to 2004 is reviewed. A total of 30 patients who were exposed to lithium during gestation with adequate clinical description were identified. A significant number of these babies presented with neurodevelopmental deficits and depressed neurological status including hypotonia, respiratory distress syndrome, cyanosis, lethargy, and weak suck and Moro reflexes in the neonatal period. The majority of these abnormalities resolved and most babies made full recovery. Other abnormalities were structural as well as functional involvement of the cardiovascular system, macrosomia, prematurity, jaundice, diabetes insipidus, and involvement of the thyroid gland. While the use of lithium during pregnancy does not appear to significantly increase the risk of congenital anomalies, it is frequently associated with perinatal complications and reversible neonatal toxicity. Suggested guidelines for appropriate monitoring of infants and breast-feeding of exposed babies are presented. In addition, prenatal surveillance of women with bipolar disorders who are being treated with lithium is briefly discussed.
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PMID:Neonatal toxicity and transient neurodevelopmental deficits following prenatal exposure to lithium: Another clinical report and a review of the literature. 1563 73

A new case of severe clinical phenotype of the cat-eye syndrome: We report on a female infant with severe clinical phenotype of Cat-Eye Syndrome (CES). At birth, she had respiratory distress and marked hypotonia. Physical examination showed major craniofacial anomalies including microcephaly, bilateral total absence of the external ears, hypertelorism, bilateral ocular coloboma of iris and micrognathia. In addition, she had anal stenosis, a patent ductus arteriosus and intra- and extra- hepatic biliary atresia. She deteriorated with the development of bradycardia. She died at age one month of cardiac failure. Cytogenetic analysis of the proband showed an extra de novo small bisatelllited marker chromosome in all cells examined. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified the marker as a CES chromosome. Thus, the patient's karyotype was: 47, XX, +idic(22)(pter-->q11.2 ::q11.2-->pter). The duplication breakpoints giving rise to the CES chromosome were distal to the DiGeorge Syndrome (DGS) locus 22q11.2. The marker could be classed as a type 11 symmetrical (10). According to a recent review of CES literature (1) only 41 % of the CES patients have the combination of iris coloboma, anal anomalies and preauricular anomalies. Almost 60% are hard to recognize by their phenotype alone. Only twelve patients showed a severe clinical phenotype leading to the death of the child. This phenotypic variability increases the difficulties of genetic counseling.
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PMID:A new case of a severe clinical phenotype of the cat-eye syndrome. 1565 20


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