Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexosaminidase deficiency diseases or GM2-gangliosidoses were originally described as infantile encephalopathies. Recently, hexosaminidase deficiencies have been found with different phenotypes, including juvenile and adult encephalopathies, cerebellar ataxias, and motor neuron diseases. Individual cases have resembled Ramsey-Hunt syndrome, olivopontocerebellar ataxia, Friedreich ataxia, amyotrophic lateral sclerosis, Kugelberg-Welander disease, Fazio-Londe disease, and Charcot-Marie-Tooth disease. Tremor, dystonia, spastic paresis, and psychosis have been seen. Since few diagnosable causes for these system atrophies are known, these patients should be tested for hexosaminidase deficiency. These recessive disorders fit a multiple loci/multiple alleles genetic scheme, and a clinical genetic classification is presented.
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PMID:The clinical spectrum of hexosaminidase deficiency diseases. 719 92

This report describes a case of a 17-year-old girl with Charcot-Marie-Tooth disease (CMT) representing rigid spine and respiratory failure. At age 11, she tended to walk on her toes and had difficulty in getting up from the floor without support. She became aware of flexion limitation of the neck at the age of 12. At 15 years of age, She began to have dyspnea on effort. When she was 17 years old, neurological examination revealed mild weakness of the upper extremities and severe weakness of the distal lower extremities, generalized wasting and areflexia. Superficial sensation was mildly impaired distally, and vibration sensation was severely impaired in the lower extremities. Motor and sensory nerve conduction velocities were mildly reduced, and compound muscle action potential of the tibial and peroneal nerves and sensory nerve action potential on ulnar and sural nerves were absent. Electromyography showed neurogenic changes with denervation potentials. Sural nerve biopsy revealed severe loss of myelinated fibers without any onion-bulb formation. As for family history, her elder sister showed moderate loss of vibration sensation in the lower extremities. On the basis of these findings, she was diagnosed as having CMT type 2, though a mode of inheritance was uncertain. She also had peculiar findings of flexion limitation of the spine (rigid spine), contracture of the hip joint, and fatty degeneration of paraspinal muscles on CT. Percent vital capacity (VC) was 22.5%, and arterial blood gas analysis showed PaO2 of 60.5 mmHg and PaCO2 65.0 mmHg. To our knowledge, this is the first case of CMT accompanied by rigid spine and respiratory failure. Motor and sensory neuropathy combined with rigid spine also have not been reported previously. The relationship between rigid spine syndrome with neurogenic muscular atrophy and CMT type 2C with the clinical characteristics of diaphragm and vocal cord paresis is discussed.
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PMID:[A patient of Charcot-Marie-tooth disease with rigid spine and respiratory failure]. 1100 24

Charcot-Marie-Tooth disease (CMT), or hereditary motor and sensory neuropathy (HMSN), includes two main subtypes of CMT1/HMSN I (demyelinating), and CMT2/HMSN II (axonal). Further heterogeneity has been demonstrated by genetic molecular studies, with at least four responsible genes for CMT1. As for CMT2, a mutation in the neurofilament-light (NF-L) gene has been identified in a single family, and other CMT2 loci have been mapped. We propose a clinical classification of the CMT2 phenotypes, and review the features of the identified CMT2 genotypes. The following main subtypes of CMT2 are considered in the phenotype classification: classical CMT2, the variants of CMT2 showing atypical features that may represent either variance in the classical CMT2 phenotype or separate entities; CMT2 plus, i.e. complex forms with involvement of additional neural structures. The recognized CMT2 genotypes include: CMT2A (mapped to chromosome 1p35-36); CMT2B (3q13-22); CMT2C (with vocal cord paresis); CMT2D (7p14); CMT2E, related to a mutation in the NF-L gene on chromosome 8p21; proximal CMT2, or HMSN P (3q13.1); CMT2 with MPZ mutations; autosomal recessive CMT2 (1q21.2-q21.3); agenesis of the corpus callosum with sensorimotor neuronopathy (15q13-q15); CMT2 X-linked with deafness and mental retardation (Xq24-q26). The identified genotypes may correspond to previously described clinical subtypes of CMT2. In particular, classical CMT2 presents in association with NF-L gene mutation, in the only CMT2 family with known gene mutation, and in CMT2A patients. However, the features of classical CMT2 have been paradoxically reported also in families with MPZ mutation, and conversely several CMT2 families are not linked to the known CMT2 loci. Further cloning of the CMT2 genes will ultimately shed light on the pathogenic mechanism(s) implicated in the process of axonal degeneration, shared by the different CMT2 genotypes.
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PMID:Charcot-Marie-Tooth disease (CMT): distinctive phenotypic and genotypic features in CMT type 2. 1123 Oct 25

No cohesive overview of vocal fold abnormalities associated with Charcot-Marie-Tooth disease (CMT) has been presented in the literature. This study examines a patient in depth and compares the findings with those of published reports to characterize the features of vocal fold paresis in CMT. The affected patient was investigated with nerve conduction testing, laryngeal electromyography, endoscopy, and laryngeal sensory testing. Ten published cases were reviewed for similarities and differences. Vocal fold paresis has been observed in 11 CMT patients ranging in age from 8 to 80 years. Two cases have occurred in the context of CMT type 1, and 9 in CMT type 2. Seven of the 11 cases (64%) were clearly bilateral; only 2 of the 7 cases (29%) required tracheotomy, and both were in children. The electromyographic findings were typical of reinnervation. Sensory findings were present, but did not represent significant disability in the 1 patient so studied. We conclude that CMT does not spare the cranial nerves, as has been previously thought. Furthermore, vocal fold paresis is not restricted to CMT type 2 and should not be considered a hallmark of that category. The available evidence suggests that the neural deficit evolves gradually, may exhibit partial recovery, and often escapes notice for a time. Vocal fold abnormalities are most often bilateral. Because the deficit is generally well tolerated in adults, many cases have probably been overlooked, and no conclusion regarding incidence is possible. Nevertheless, the potential for airway compromise exists, especially in children. Respiratory complaints of CMT patients should be thoroughly investigated.
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PMID:Vocal fold paresis of Charcot-Marie-Tooth disease. 1171 21

We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes.
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PMID:The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. 1174 80

Three Spanish families with an autosomal recessive severe hereditary motor and sensory neuropathy, showing mutations in the ganglioside-induced-differentiation-associated protein 1 (GDAP1) gene in the Charcot-Marie-Tooth (CMT) type 4A locus were studied. The disorder started in the neonatal period or early infancy with weakness and wasting of the feet and, subsequently, involvement of the hands, causing severe disability. By the late teens, some patients developed a hoarse voice and vocal cord paresis. Peripheral motor nerve conduction velocity (MNCV) could not be measured in many cases because of the absence of muscle response due to distal atrophy. However, latencies to proximal muscles were in the normal range; median MNCV was >40 m/s in those cases in which it could be measured. Sural nerve biopsy from two patients showed a pronounced depletion of myelinated fibres, regenerative clusters and signs of axonal atrophy. Additionally, a small proportion of thin myelinated fibres and proliferation of Schwann cells forming onion bulb structures were also found. Unmyelinated fibre population was markedly increased. These findings are indicative of a predominant axonal degeneration with some demyelinating features. These Spanish families share in the severe CMT clinical phenotype with some Tunisian families who also presented mutations in the GDAP1 gene and to which the CMT4A locus was originally assigned. However, our families differ in the presence of laryngeal involvement and values of MNCV and pathological features are more in line with CMT2 type. The possibility that GDAP1 gene mutations could be expressed under different phenotypes is a question to be resolved.
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PMID:Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene. 1282 18

Mutations in the ganglioside-induced differentiation-associated protein 1 gene cause either autosomal recessive demyelinating Charcot-Marie-Tooth disease type 4A or autosomal recessive axonal Charcot-Marie-Tooth disease with vocal cord paresis. We sequenced the ganglioside-induced differentiation-associated protein 1 gene in 138 patients from 119 unrelated families diagnosed with either demyelinating or axonal autosomal recessive Charcot-Marie-Tooth disease. We detected six distinct mutant alleles in four families, four of which are novel. Electrophysiological studies show severely slowed motor nerve conduction velocities with severely reduced compound muscle action potentials. However, one patient had a normal conduction velocity in the ulnar nerve. Based on the electrophysiological tests, patients with ganglioside-induced differentiation-associated protein 1 mutations will therefore be classified as either axonal or demyelinating Charcot-Marie-Tooth disease. The neuropathological aspect shows a divergent pattern; nerve biopsies taken from two siblings at the same age and sharing the same ganglioside-induced differentiation-associated protein 1 gene mutation showed a dissimilar severity stage.
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PMID:Identification of novel GDAP1 mutations causing autosomal recessive Charcot-Marie-Tooth disease. 1456 95

Inherited neuropathies are clinically and genetically heterogeneous. At least 28 genes and 12 loci have been associated with Charcot-Marie-Tooth disease (CMT) and related inherited neuropathies. Most causes of inherited neuropathy have been discovered by positional cloning technique and in the past two years, the pace of CMT gene discovery has accelerated. Genetic studies have revealed the following gene mutations as the causes of inherited neuropathies; PMP22, MPZ, EGR2, SOX10, SIMPLE/LITAF, ARHGEF10 for CMT1 (autosomal dominant demyelinating form); GDAP1, MTMR2, SBF2/MTMR13, KIAA1985, NDRG1 PRX for CMT4 (autosomal recessive demyelinating form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 for CMT-DI (autosomal dominant CMT with intermediate nerve conduction velocities); and DHH for minifascicular neuropathy. These discovered CMT causing genes/proteins include those which show unpredictable correlations with the peripheral nervous system. However, these genes/proteins are definitely important for the peripheral nerve, and their discovery should pave the way for dramatic progress in the understanding of peripheral nerve biology. On the other hand, genotype-phenotype correlations of these genes are also important in order to understand the pathomechanisms of inherited neuropathy. Because, based on mutation studies, a large number of genes associated with both the CMT1/4 and CMT2 forms have been identified, it is usually difficult to predict the causative gene based on clinical information from patients without specific complications. To clarify the specific features and molecular mechanisms of five diseases that we previously reported, we reviewed recent progress in HMSN-P linked to chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 caused by SBF2/MTMR13, and SCAN1 caused by TDP1. HMSN-P is characterized by late onset, proximal dominant severe muscle weakness, fasciculations, muscle cramp and sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin are associated with a broad spectrum of demyelinating neuropathies including DSS, a sensory dominant form and early onset slowly progressive CMT. Pathologically, loss of myelinated fibers, demyelination, small onion bulb formations, tomacula formation and myelin foldings were seen in sural nerves. Absence of septate like junction in the paranodal loop suggests that periaxin could be required for the adhesion complex. GDAP1 is a relatively common cause of CMT4. Half of reported patients showed the demyelinating form, while the rest showed the axonal form. The typical feature of CMT4A is paresis of the vocal cords and diaphragm. CMT4B2 is characterized by autosomal recessive, juvenile onset glaucoma and focally folded myelin in sural nerves. SBF2/MTMR13 mutations cause CMT4B2. Early onset glaucoma was seen in patients with nonsense mutations. SBF2/MTMR13 and MTMR2, which is the cause of CMT4B1, could be acting on the same 3-phosphoinositide signaling pathway. Clinical phenotypes of patients with TDP1, APTX, or SETX mutations share common clinical findings, namely cerebellar ataxia and axonal neuropathy. TDP1 and aprataxin both act on the single strand break repair pathway, with TDP1 working specifically on topoisomerase I related SSBR. Senataxin is a RNA helicase acting on RNA maturation and termination in yeast. Since these three proteins share a common pathway, disruption in any of them could induce a delay in the transcription process. The low rate of protein supply could lead to deaths of large neuronal cells.
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PMID:[Molecular genetics of inherited neuropathies]. 1654 90

Silver syndrome (Silver spastic paraplegia syndrome) is a rare disorder of the peripheral nervous system that combines features of spastic paraparesis and peripheral neuropathy. The underlying genetic defects are two mutations in the BSCL2 gene which have been described in several families. Silver syndrome--related to the N88S mutation in the BSCL2 gene--is characterized by a spectrum of clinical findings. The coexistence of sensory fiber damage and motor deficit leads to the diagnosis of Charcot-Marie-Tooth disease in some patients, while others are diagnosed with spastic paresis due to predominant pyramidal symptoms. If the symptoms are limited to the motor deficit, hereditary motor neuropathy is diagnosed in some cases. In this report, we describe a case of the Silver syndrome in a Polish family that has been verified by genetic testing. Due to the lack of pyramidal symptoms and slightly expressed sensory fiber damage (in neurographic studies), motor neuropathy type of the Silver syndrome with minor sensory component was diagnosed.
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PMID:[Silver syndrome--case report]. 1822 79

Cranial nerve involvement in Charcot-Marie-Tooth disease (CMT) is rare, though there are a number of CMT syndromes in which vocal cord paralysis is a characteristic feature. CMT disease due to mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) has been reported to be associated with vocal cord and diaphragmatic palsy. In order to address the prevalence of these complications in patients with GDAP1 mutations we evaluated vocal cord and respiratory function in nine patients from eight unrelated families with this disorder. Hoarseness of the voice and inability to speak loudly were reported by eight patients and one had associated symptoms of respiratory insufficiency. Patients were investigated by means of peripheral and phrenic nerve conduction studies, flexible laryngoscopy, pulmonary function studies and polysomnography. Nerve conduction velocities and pathological studies were compatible with axonal CMT (CMT2). Flexible laryngoscopy showed left vocal cord palsy in four cases, bilateral cord palsies in four cases and was normal in one case. Restrictive respiratory dysfunction was seen in the eight patients with vocal cord paresis who were all chair-bound. These eight had confirmed phrenic nerve dysfunction on neurophysiology evaluation. The patient with normal vocal cord and pulmonary function had a less severe clinical course.This study shows that CMT patients with GDAP1 mutations develop severe disability due to weakness of limb muscles and that laryngeal and respiratory muscle involvement occurs late in the disease process when significant proximal upper limb weakness has developed. The early and predominant involvement of the left vocal cord innervated by the longer left recurrent laryngeal nerve suggests a length dependent pattern of nerve degeneration. In GDAP1 neuropathy, respiratory function should be thoroughly investigated because life expectancy can be compromised due to respiratory failure.
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PMID:Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptoms of GDAP1-associated neuropathy. 1881 41


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