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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked myotubular myopathy is a severe congenital myopathy that presents in the neonatal period with profound hypotonia and an inability to establish spontaneous respiration. Usually death occurs in infancy from respiratory failure. However, there is phenotypic variability; a number of affected boys have achieved respiratory independence and become ambulatory. Disease-causing mutations have been identified throughout the MTM1 gene on Xq28. MTM1 encodes the protein myotubularin, which is expressed ubiquitously. The main objectives of this study were to establish whether the nature or site of the mutation in the MTM1 gene could predict severity of the disease and to investigate whether early intensive clinical intervention facilitated survival until spontaneous improvement occurred. An association was demonstrated between the presence of a non-truncating mutation of the MTM1 gene and the mild phenotype. However, many non-truncating mutations were also seen in association with the severe phenotype and these were not confined to recognized functional domains of the protein. This suggests that the use of mutation analysis to predict prognosis in the early period following diagnosis is limited. Unexpectedly, over 50 patients surviving for more than 1 year were identified in this study. Further information obtained on 40 of these cases revealed that 50% were receiving 24-h ventilatory support, while 27% were ventilated at night only. The high survival rate for this disorder therefore reflects intensive medical intervention without which the majority of these boys would not survive.
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PMID:Genotype-phenotype correlations in X-linked myotubular myopathy. 1246 49

Causes of hypotonia in the newborn can be broadly categorized into two classifications. Hypotonia with a supraspinal origin may be seen with systemic disease, hypoxic ischemic encephalopathy, cerebral malformations, syndromes (for example: Down, Prader-Willi, Lowe, Zellweger, Smith-Lemli-Opitz), and c-spine injury. Disorders of the motor unit that present with hypotonia in the newborn period include SMA, congenital myotonic dystrophy, congenital myasthenia gravis, and congenital myopathies. Central core disease is one of the classic congenital myopathies that can be differentiated based on characteristic histologic findings. Muscle fiber samples from patients with central core disease possess distinct morphology that can be diagnostic. Many infants may not exhibit muscle weakness in the newborn period, although there have been rare cases of profound hypotonia and respiratory failure. Clearly, muscle biopsy is the gold standard and is indicated for any infant with marked hypotonia that is not thought to be supraspinal in origin.
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PMID:The hypotonic infant: case study of central core disease. 1259 91

A term male newborn, appropriate for gestational age, developed hypothermia, severe cardiac dysrrhythmia, and nonoliguric hyperkalemia within 24 hours of birth. Despite the prenatal identification of cystic renal dysplasia without oligohydramnios, at birth, a solitary left leg vascular hemangioma and large palpable kidneys were the only anomalies. Gradually hypotonia, lethargy, and poor feeding developed and by 20 hours of age recurrent cardiac dysrrhythmias, myocardial dysfunction, and renal insufficiency with intermittent hyperkalemia were apparent. Episodes of apnea developed on day 7 followed by respiratory failure, recurrent cardiac dysrrhythmias, and death on day 12. Eventually laboratory and autopsy findings confirmed the diagnosis of lethal neonatal carnitine palmitoyltransferase II deficiency.
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PMID:Lethal neonatal carnitine palmitoyltransferase II deficiency: an unusual presentation of a rare disorder. 1263 78

Pontocerebellar hypoplasia type 1 is a rare disease characterized by pontocerebellar hypoplasia and anterior horn cell degeneration. The oldest reported child died at the age of 26 months. Two siblings were diagnosed with pontocerebellar hypoplasia type 1 after the death of the second sibling at 40 months of age from respiratory failure and the unexpected finding of anterior horn cell degeneration on her autopsy. The older sibling was a boy who was labeled as having cerebral palsy. He died at 14 months of age from pneumonia following a clinical course similar to his sister's, who was born 5 years after his death. Both siblings had significant global developmental delay with axial and peripheral hypotonia initially. Peripheral hypertonia with brisk reflexes developed later but were absent prior to death. Extensive investigations in the second sibling ruled out known metabolic (including congenital disorders of glycosylation) and mitochondrial diseases using skin fibroblast cultures and enzyme analysis. Genetic testing for Friedreich's ataxia; neuropathy, ataxia, and retinitis pigmentosa (NARP); spinal muscular atrophy; and spinocerebellar ataxia type 1, 2, 3, 6, 7, and 8 gene abnormalities was negative. The elecroretinogram showed a previously unreported finding of abnormal and progressive rod/cone response. Our cases provide clinical and previously unreported electroretinographic evidence for neurodegeneration in pontocerebellar hypoplasia type 1 and call for the expansion of the disease phenotype.
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PMID:Pontocerebellar hypoplasia type 1: new leads for an earlier diagnosis. 1273 47

Thirty years ago, M. H. Brooke coined the term "congenital fiber type disproportion" (CFTD) to describe 12 children who had clinical features of a congenital myopathy and relative type 1 fiber hypotrophy on muscle biopsy. It is now clear that this histological pattern can accompany a wide range of neurological disorders, leading to disillusionment with CFTD as a distinct nosological entity. To determine whether the CFTD has clinical utility as a diagnostic entity, we have reviewed the literature for cases of type 1 fiber hypotrophy and have used strict exclusion criteria to identify 67 cases of CFTD. Most patients presented at birth with weakness and hypotonia, had normal intelligence, and followed a static or improving clinical course. In 43% of families, more than 1 individual was affected. Failure to thrive was common and 25% of patients had contractures or spinal deformities. Bulbar weakness and ophthalmoplegia were less common and cardiac involvement was rare. Twenty-five percent followed a severe course and 10% had died at the time of reporting, all from respiratory failure. Ophthalmoplegia and facial and bulbar weakness were significantly associated with a poorer prognosis. The relatively homogeneous phenotype supports the retention of CFTD as a distinct diagnostic entity and familial occurrence suggests a genetic basis. Regarding the diagnosis of CFTD, we found no strong evidence that the minimum difference between type 1 and type 2 fiber sizes should be increased from 12% to 25%. We also list the other reported causes of relative type 1 fiber hypotrophy to aid their exclusion from CFTD.
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PMID:Congenital fiber type disproportion--30 years on. 1457 34

Autopsy is invaluable in identifying the causes of severe depression and very low Apgar score after birth and in assessing contributory conditions. Brain scans are increasingly used in the care of neonates who fail to respond to resuscitation at birth but their interpretation depends on the information gained from sound neuropathological studies. Asphyxia, both acute intrapartum asphyxia and chronic asphyxia, is an important cause of low Apgar scores. The gestational age and the nature of the asphyxial insult both have a profound influence on the ultimate pattern of injury. Asphyxia in the preterm brain tends to damage preferentially the white matter but some white matter damage is also seen in many infants who have an hypoxia-ischaemic insult at term though the predominant site of injury is to the central grey matter. The nature of the cellular damage and reactive change seen at autopsy is described. There is an association between low Apgar scores and intrauterine exposure to infection and maternal pyrexia. Detailed autopsy examination should include the search for infection. The placenta, cord and membranes should be examined in view of the mounting evidence of the association between intrauterine infection of the placenta and fetal membranes and prenatal brain damage. Additionally, the presence of placental thrombosis and infarction should be sought in relation to focal and global injury in the full term infant. Acquired prepartum lesions rarely cause the infant to present with a low Apgar score. The exception to this is severe damage to the brainstem and basal ganglia. Traumatic injury to the brain is now much less common than in previous decades. Subdural haemorrhage occurs more frequently than intraventricular or subarachnoid haemorrhage. Instrumental and assisted deliveries are associated with an increased incidence of subdural haemorrhage though these rarely cause significant long term damage. Careful autopsy, particularly of the neck and paravertebral tissues, spinal cord, brainstem and nerve roots is important where trauma is suspected. Tearing of nerve roots or fibre bundles in the spinal cord is readily demonstrated under the microscope using immunocytochemistry to beta-amyloid precursor protein. Disorders of the spinal cord, peripheral nerve and muscle as well as some metabolic diseases may cause a baby to be both floppy and weak. Metabolic disease, including peroxisomal disorders, non-ketotic hyperglycinaemia, lipid and glycogen storage disorders and mitochondrial diseases may cause profound hypotonia and respiratory failure at birth or shortly afterwards.
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PMID:The value of autopsy in determining the cause of failure to respond to resuscitation at birth. 1525 Nov 49

Congenital disorders of glycosylation (CDG) represent a newly delineated group of inherited multisystem disorders characterized by defective glycoprotein biosynthesis. In the present study we report and discuss the clinical and neuropathological findings in a newborn with CDG type Ia (CDG-Ia). The patient presented mild dysmorphic facial features, inverted nipples, progressive generalized edema, hypertrophic cardiomyopathy, hepatosplenomegaly, muscular hypotonia and had severe hypoalbuminemia. Deficiency of phosphomannomutase (PMM)-2 activity was detected. Molecular analysis showed V231M/T237R mutations of the PMM2 gene. Muscular biopsy, disclosed myopathic alterations with myofibrillar disarray by electron microscopy. The patient died at 1 month of age of circulatory and respiratory failure. Autopsy showed liver fibrosis and renal abnormalities. Neuropathological abnormalities were mainly confined to the cerebellum. Histological and immunocytochemical examination of cerebellar tissue showed partial atrophy of cerebellar folia with severe loss of Purkinje cells, granular cell depletion and various morphological changes in the remaining Purkinje cells and their dendritic arborization. Autopsy findings confirm the complexity of the CDG-Ia syndrome, and indicate that CDG-Ia is a distinct disease entity, which can be differentiated from other neurological disorders and other types of CDG, not only clinically, but also based on unique pathological findings. The data proved useful in determining the underlying disease process associated with a defective N-glycosylation pathway.
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PMID:Congenital disorder of glycosylation type Ia: a clinicopathological report of a newborn infant with cerebellar pathology. 1571 16

Spinal muscular atrophies are a clinically and genetically heterogeneous group of disorders. Atypical forms of the disease have also been described, including those with associated sensory deficits, hearing loss, cerebellar hypoplasia, congenital heart defects, arthrogryposis, and bone fractures at birth. The patient described here is a male infant, born to a 30-year-old mother at 34 weeks of gestation complicated with polyhydramnios. The first son of consanguineous parents had died with the same clinical features. The patient required ventilatory support because of respiratory failure after the birth and died on day 13. His physical examination revealed profound generalized hypotonia, absence of deep tendon and neonatal reflexes, dysmorphic facies, arthrogryposis, clinodactyly, and left femur fracture. A muscle biopsy revealed variation in fiber size with occasional hypertrophic fibers. The postmortem examination revealed loss and degeneration of anterior horn cells. We propose that the patient, who presented with severe hypotonia, femur fracture, arthrogryposis, dysmorphic features, history of early death of his brother with the same clinical features and parental consanguinity, had probable X-linked spinal muscular atrophy. However, autosomal-recessive inheritance can not be completely excluded.
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PMID:Severe lethal spinal muscular atrophy variant with arthrogryposis. 1573 Sep 3

Patients with Leigh syndrome classically present in early childhood with developmental regression, ataxia, and hypotonia with subsequent respiratory and brainstem dysfunction. However, the clinical presentation can be highly variable. This report presents five cases of Leigh syndrome with atypical presentations. The first patient is a 17-month-old female who presented with progressive limb weakness diagnosed as Guillain-Barre syndrome. Postmortem examination demonstrated Leigh syndrome confined to the spinal cord. The case series then describes two sisters one of whom presented at 11 years of age with central respiratory failure and encephalopathy. Her 15-year-old sister presented with a progressive diplegia. The fourth patient presented with bronchiolitis and apnea at 3 months of age due to bilateral brainstem lesions. Her second cousin presented at 6 months of age with hypotonia, blindness, and tonic seizures. All patients had laboratory and radiologic findings consistent with Leigh syndrome. Evidence of spinal cord involvement was observed on magnetic resonance imaging in four of the five patients. Leigh syndrome can involve any level of the neuroaxis, resulting in a wide variety of presentations. Many atypical variants are observed, of which clinicians should be aware. Evidence of brainstem or spinal cord involvement should also be sought in patients with Leigh syndrome.
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PMID:Atypical presentations of leigh syndrome: a case series and review. 1586 34

This paper describes the second patient found to be affected with a deficiency of transaldolase (TALDO1; EC 2.2.1.2). Clinically, this patient presented in the neonatal period with several signs of severe liver failure: severe coagulopathy, low serum protein, elevated blood ammonia, and hypoglycaemia. She had generalized oedema, moderate muscular hypotonia, and dysmorphic signs. Liver size was decreased, and the spleen was moderately enlarged. There was severe cardiomegaly. The clinical course was characterized by intractable liver failure and progressive myocardial hypertrophy. The child died at the age of 18 days from respiratory failure. In urine, elevations of erythritol, arabitol and ribitol were found, suggesting a deficiency of transaldolase. Enzyme studies in cultured fibroblasts showed undetectable transaldolase activity. DNA sequence analysis of the TALDO1 gene showed a homozygous missense mutation (575G>A), resulting in an amino acid alteration at position 192 (arginine to histidine, R192H). This amino acid is part of the catalytic site of the transaldolase protein. Discovery of this second patient affected with transaldolase deficiency and liver failure suggests that this disorder has a heterogeneous clinical presentation with highly variable severity.
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PMID:A newborn with severe liver failure, cardiomyopathy and transaldolase deficiency. 1587 6


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