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PubMedDate not supplied

Labor analgesia and anesthesia in a patient with spinal muscular atrophy and vocal cord paralysis. A rare and unusual case report.

BACKGROUND AND OBJECTIVES: A case of labor analgesia and anesthesia in a 23-year-old woman with spinal muscular atrophy and vocal cord paralysis is reported. As spinal muscular atrophy is a progressive degenerative disorder of spinal anterior horn cells, with generalized neuromuscular weakness as a common sequela, the goal of anesthetic management is to provide satisfactory labor analgesia and anesthesia with minimal compromise of respiratory function. METHODS: A lumbar epidural anesthetic technique was used to provide satisfactory labor analgesia and anesthesia for a low forceps delivery. RESULTS: The anesthetic technique provided a safe delivery. As the patient was awake, she was able to assist with the expulsion phase of labor. The rare published reports of spinal muscular atrophy and obstetric management are reviewed, the known pertinent physiologic derangements of the syndrome in concert with pregnancy being detailed, along with any information provided regarding anesthetic techniques. CONCLUSIONS: It is believed that labor analgesia and anesthesia can be provided adequately with lumbar epidural techniques. An understanding of the physiology underlying spinal muscular atrophy is essential to safe anesthetic management of the laboring parturient.

Adult↗
PubMed1990

Clinical and electromyographic studies of postpoliomyelitis muscular atrophy.

Eleven patients with progressive weakness following polio (postpoliomyelitis muscular atrophy syndrome) were compared electromyographically with nine patients who had stable strength following polio. Abnormalities included (1) abnormal motor unit characteristics in many muscles indicating widespread loss of motor neurons and reinnervation in muscles, including many not clinically affected by the polio; (2) prevalent spontaneous denervation potentials; and (3) abnormal single-fiber electromyographic jitter. These electromyographic abnormalities were similar in progressive and stable postpoliomyelitis patients even when muscles were separated by strength, stability, age and duration of the postpoliomyelitis state. Postpoliomyelitis muscular atrophy appears to be the clinically apparent end of the spectrum of abnormalities existing in all postpoliomyelitis patients.

Action Potentials↗
PubMed1997

Deletion and conversion in spinal muscular atrophy patients: is there a relationship to severity?

The spinal muscular atrophy-determining gene, survival motor neuron (SMN), is present in two copies, telSMN and cenSMN, which can be distinguished by base-pair changes in exons 7 and 8. The telSMN gene is often absent in spinal muscular atrophy patients, which could be due to deletion or sequence conversion (telSMN conversion to cenSMN giving rise to two cenSMN genes). To test for conversion events in spinal muscular atrophy, we amplified a 1-kb fragment that spanned exons 7 and 8 of SMN from 5 patients who retained telSMN exon 8 but lacked exon 7. In all patients, sequence analysis demonstrated that cenSMN exon 7 was adjacent to telSMN exon 8, indicating conversion. All 5 patients with this mutation had type II or III spinal muscular atrophy, strongly supporting an association with chronic spinal muscular atrophy. We also identified 3 families in which 2 siblings had no detectable telSMN but presented with markedly different phenotypes. We suggest that sequence conversion is a common event in spinal muscular atrophy and is associated with the milder form of the disease. The severity, however, can be modified in either a positive or negative direction by other factors that influence splicing or expression of the sequence converted SMN gene.

Base Sequence↗
PubMed1999

Preimplantation genetic diagnosis for spinal muscular atrophy type I.

OBJECTIVE: Couples with children who have spinal muscular atrophy type I (SMA) face a 25% risk of having affected offspring with spontaneous conception. Preimplantation genetic testing (PGT) is possible for the deletions in the survival motor neuron (SMN) gene that have been identified in 98% of SMA type I cases. PGT would provide new reproductive options for families at risk for SMA. METHODS: Three couples with previously affected children confirmed by DNA testing each underwent in vitro fertilization (IVF) and PGT of the resulting embryos. One or two blastomeres were biopsied from each embryo and analyzed for deletions in exons 7 and 8 of the SMN gene. RESULTS: Nine embryos were predicted to be unaffected, three to be affected, and one embryo could not be interpreted. One of three patients receiving transfer of unaffected embryos became pregnant with twins. CONCLUSIONS: Preimplantation genetic testing provides a means for couples at risk for spinal muscular atrophy type I to reduce their chance of initiating an affected pregnancy.

Adult↗
PubMed2005

Transmission ratio distortion in the spinal muscular atrophy locus: data from 314 prenatal tests.

BACKGROUND: Spinal muscular atrophy (SMA) is a recessive neurodegenerative disorder characterized by the loss of alpha-motor neurons in the spinal cord and subsequent death of motor neuron cells. SMA occurs with a frequency of 1 in 6,000 live births, with a carrier frequency of 1 in 40, and is a leading genetic cause of infant mortality. SMA is caused by loss or mutation of the telomeric survival motor neuron gene (SMN1), which is deleted in almost 94% of SMA patients OBJECTIVE: To analyze the transmission ratio at the SMA locus, examining the segregation of the SMN1-deleted alleles in 314 fetuses from carrier parents who requested prenatal testing for the disease. METHODS: Prenatal diagnosis of SMA in families at 25% risk of the disease has been performed on chorionic villous sampling specimens, through direct detection of the SMN1 gene mutation and linkage analysis using microsatellite markers from the 5q13 region. Analysis of the genotypic/allelic frequencies of the SMN1 gene was performed using the chi2 test, assuming a recessive mendelian inheritance. RESULTS: Of 314 fetuses analyzed, 95 were homozygous for the wild-type allele (30.3%), 154 were carriers (49.0%), and the remaining 65 were homozygous for the mutated allele (20.7%). Statistical analysis demonstrated that proportion of fetuses predicted with SMA is lower than 25% expected for a recessive disorder, resulting in a transmission rate of the SMN1-deleted allele deviant from the 50% expected in a random the segregation of a mendelian tract (p = 0.016) CONCLUSIONS: This is the first study to evaluate the genotypic frequencies at the spinal muscular atrophy (SMA) locus based on data derived from prenatal analysis, which are not subject to ascertainment bias. The analysis showed a transmission ratio distortion at the SMA locus in favor of the SMN1 wild-type alleles.

Chorionic Villi Sampling↗
PubMed2026

A novel ASCC1 splice-site variant broadens the phenotypic spectrum of spinal muscular atrophy with congenital bone fractures type 2.

Spinal muscular atrophy with congenital bone fractures type 2 (SMABF2) is an ultra-rare neuromuscular disorder caused by pathogenic variants affecting the ASC-1 complex, most commonly ASCC1. The disorder is typically characterized by severe congenital hypotonia, prenatal or congenital fractures, and early respiratory failure. We report a girl with a novel homozygous intronic donor-site variant, c.95+5G>C, in ASCC1. In contrast to the classic SMABF2 phenotype, she had no congenital fractures and survived until 7 years of age. Her clinical presentation included generalized hypotonia, areflexia, minimal spontaneous movements, dysmorphic features related to fetal hypomobility, progressive respiratory insufficiency requiring tracheostomy and gastrostomy, and cardiac involvement. This case expands both the genetic and phenotypic spectrum of ASCC1-associated disease. The comparatively prolonged survival and absence of congenital fractures suggest that not all ASCC1 variants result in a fully loss-of-function phenotype. However, this interpretation remains hypothetical because functional RNA studies were not performed.

Humans↗
PubMed1995

Mapping of a distal form of spinal muscular atrophy with upper limb predominance to chromosome 7p.

An autosomal dominant distal form of spinal muscular atrophy mainly affecting the upper limbs with a mean age of onset of 17 years has been identified in a large Bulgarian family. Linkage of the above family to the spinal muscular atrophy type I, II and III locus on chromosome 5 has been excluded. In an attempt to map this disease gene we have analysed individuals of this family, with more than 140 microsatellite polymorphic markers of the human genome. A maximum lod score of 5.99 at theta = 0.007 has been obtained with locus D7S795. We have thus mapped the gene for this hereditary form of distal spinal muscular atrophy to chromosome 7p.

Adolescent↗
PubMed1993

[A case of distal spinal muscular atrophy].

A 13-year-old boy with distal spinal muscular atrophy was reported. He noted atrophy of the bilateral legs since 11 years old. Ankle jerk was brisk and pes cavus was observed. Needle EMG of the leg showed denervation pattern. Muscle biopsy of the gastrocnemius muscle revealed large group atrophy and fiber type grouping. MCV, SCV and results of sural nerve biopsy were normal. We diagnosed his disorder as distal muscular atrophy. The essential lesion of this disease was supposed to be in the anterior horn cells.

Adolescent↗
PubMed2005

Bovine spinal muscular atrophy: AFG3L2 is not a positional candidate gene.

Bovine spinal muscular atrophy (BSMA) is a neurodegenerative disorder, which is widespread in Brown Swiss cattle. Main symptoms of the disease are muscular atrophy and recumbency. Affected calves die within few days or weeks. BSMA seems to be inherited as a recessive trait and the disease allele appears to have a common origin. In this study, a pedigree with 30 affected BSMA calves was used to genetically localize the BSMA locus. Linkage analysis was performed between microsatellite markers of seven chromosomes, where the homologous genes of human neurodegenerative disorders are located according to comparative mapping data, and the disease genotype. BSMA was mapped to chromosome 24 confirming the recently published localization (Medugorac et al. 2003). The candidate gene AFG3L2 was physically mapped to chromosome 24q24 using fluorescence in situ hybridization. Due to their different localizations AFG3L2 is not a positional candidate for BSMA. An informative marker localized on the telomeric side of the BSMA locus would be beneficial for marker-assisted selection as well as searching for the causative gene. However, finding a marker distal to BSMA locus is difficult because of its position at the end of the chromosome.

Adenosine Triphosphatases↗
PubMed1989

Surgical and functional results of spine fusion in spinal muscular atrophy.

From 1965 to 1987, 84 spinal muscular atrophy patients were followed at Rancho Los Amigos Medical Center (RLAMC). Twenty-seven patients were excluded from this study due to insufficient medical documentation (16), lack of follow-up (5), and death (6); leaving 57 patients in the general study group. Group I (34 patients) had posterior spinal fusion (PSF) with Harrington rod instrumentation (HRI); mean age at surgery was 12 years, average preoperative curve was 57 degrees, average postoperative correction was 42%, with a loss of correction of 9 degrees. The complication rate in this group was 35%. The average follow-up interval was 9 years (range, 4-19 years). Group II (six patients) underwent PSF with Luque segmental spinal instrumentation (SSI); mean age at surgery was 11 years, preoperative curves averaged 37 degrees, average postoperative correction was 42% with a loss of correction of 3 degrees. The complication rate in this group was 16%. Follow-up was 3.5 years. Physical therapy and occupational therapy evaluations were done preoperatively and postoperatively at 2- and 5-year intervals. Information was gathered in three categories: 1) ambulation, 2) equipment use, and 3) functional activities. After fusion, sitting tolerance was maintained but additional use of mobile arm supports, lapboards, and reaching aides was necessary for all patients. The ability to perform activities such as drinking, self-feeding, and self-hygiene declined during the 2 years immediately following surgery but improved by 5 years. Surgical patients never approached their preoperative skill levels. Therapy evaluations further demonstrated that there were no difference in function between either operative group.

Adolescent↗
PubMed1992

Medical therapy in spinal muscular atrophy: a realistic expectation?

The hereditary spinal muscular atrophies (SMA) type I-III belong to those diseases for which even the thought of medical therapy seems forbidden. Two neurotrophic factors are, however, now known to exert a markedly stimulating effect on survival of motor neurons in vivo! In principle such factors may become available by recombinant DNA techniques for experiments in animal models of SMA and if these experiments are successful for clinical trials in man. Medical therapy in SMA should aim primarily at patients early in the rapidly progressive phase of their disease, before massive loss of motoneuron has taken place.

Adrenocorticotropic Hormone↗
PubMed2006

Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition.

Caveolin-3, the muscle-specific isoform of caveolins, plays important roles in signal transduction. Dominant-negative mutations of the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy 1C (LGMD1C) with loss of caveolin-3. However, identification of the precise molecular mechanism leading to muscular atrophy in caveolin-3-deficient muscle has remained elusive. Myostatin, a member of the muscle-specific TGF-beta superfamily, negatively regulates skeletal muscle volume. Here we report that caveolin-3 inhibited myostatin signaling by suppressing activation of its type I receptor; this was followed by hypophosphorylation of an intracellular effector, Mad homolog 2 (Smad2), and decreased downstream transcriptional activity. Loss of caveolin-3 in P104L mutant caveolin-3 transgenic mice caused muscular atrophy with increase in phosphorylated Smad2 (p-Smad2) as well as p21 (also known as Cdkn1a), a myostatin target gene. Introduction of the myostatin prodomain, an inhibitor of myostatin, by genetic crossing or intraperitoneal administration of the soluble type II myostatin receptor, another inhibitor, ameliorated muscular atrophy of the mutant caveolin-3 transgenic mice with suppression of p-Smad2 and p21 levels. These findings suggest that caveolin-3 normally suppresses the myostatin-mediated signal, thereby preventing muscular atrophy, and that hyperactivation of myostatin signaling participates in the pathogenesis of muscular atrophy in a mouse model of LGMD1C. Myostatin inhibition may be a promising therapy for LGMD1C patients.

Animals↗
PubMed1990

Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q.

Proximal spinal muscular atrophies represent the second most common fatal, autosomal recessive disorder after cystic fibrosis. The childhood form is classically subdivided into three groups: acute Werdnig-Hoffmann (type I), intermediate Werdnig-Hoffmann disease (type II) and Kugelberg-Welander disease (type III). These different clinical forms have previously been attributed to either genetic heterogeneity or variable expression of different mutations at the same locus. Research has been hindered because the underlying biochemical defect is unknown, and there are insufficient large pedigrees with the most common and severe form (type I) available for study. Therefore, we have undertaken a genetic linkage analysis of the chronic forms of the disease (types II and III) as an initial step towards the ultimate goal of characterizing the gene(s) responsible for all three types. We report here the assignment of the locus for the chronic forms to the long arm of chromosome 5 (5q12-q14), with the anonymous DNA marker D5S39, in 24 multiplex families of distinct ethnic origin. Furthermore, no evidence for genetic heterogeneity was found for types II and III in our study, suggesting that these two forms are allelic disorders.

Chromosome Mapping↗
PubMed2002

Spinal muscular atrophy: recent advances and future prospects.

Spinal muscular atrophies (SMA) are characterized by degeneration of lower motor neurons associated with muscle paralysis and atrophy. Childhood SMA is a frequent recessive autosomal disorder and represents one of the most common genetic causes of death in childhood. Mutations of the SMN1 gene are responsible for SMA. The knowledge of the genetic basis of SMA, a better understanding of SMN function, and the recent generation of SMA mouse models represent major advances in the field of SMA. These are starting points towards understanding the pathophysiology of SMA and developing therapeutic strategies for this devastating neurodegenerative disease, for which no curative treatment is known so far.

Adult↗
PubMed1988

A follow-up study of 60 cases of chronic spinal muscular atrophy.

60 cases of chronic spinal muscular atrophy (CSMA) were followed-up for a period varying from 5 to 40 years. The neuromuscular impairment was evaluated by Norris' ALS score, both at the time of last examination and retrospectively at the time of diagnosis. Age at onset of symptoms was the most important factor in the progression of the neuromuscular damage. Monomelic or asymmetric location of symptoms at the time of diagnosis and duration of the disease were not significantly correlated to the worsening of ALS score.

Adult↗
PubMed1988

Electromyographic and computed tomographic findings in five patients with monomelic spinal muscular atrophy.

Five patients with monomelic spinal muscular atrophy are described. Clinical features included insidious onset of wasting and weakness of one limb, lack of involvement of the cranial nerves, brain stem, pyramidal tracts and sensory system, and a stable condition over a period of 4-20 years. Clinical findings, electromyography and/or muscle biopsy were consistent with anterior horn cell lesion. Central cavities were excluded by magnetic resonance imaging studies of the spinal cord. Computed tomography of skeletal musculature and electromyography indicated more diffuse lower motor neuron involvement by revealing abnormalities in clinically unaffected muscles in 4 of the 5 patients. Myokymic discharges were found in the affected limb of 1 patient.

Adolescent↗
PubMed1992

[Cervical root avulsion presenting proximal segmental muscular atrophy of unilateral upper extremity].

A 56-year-old woman noticed non-progressive weakness in the proximal part of the right upper extremity from her childhood. At the age of 37 years, she was diagnosed as "spinal muscular atrophy" by an orthopedic surgeon. At the age of 56, neurological examinations revealed muscular atrophy and weakness confined to the right deltoid, biceps brachii and brachioradialis together with minor sensory disturbance in the lateral side of the right shoulder and forearm without pyramidal sign in the lower extremities. The neurological features of this case differed from those of juvenile type of distal and segmental muscular atrophy of upper extremities in distribution of muscular atrophy, and simulated those of cervical spondylotic amyotrophy. Myelography demonstrated root avulsion of the right C5 and C6 roots. CT myelography revealed traumatic meningocele. Therefore a clinical diagnosis of cervical root avulsion resulting from unrecognized birth injury was made. The reason of motor dominant pictures of this case may be vulnerability of the anterior nerve roots to traction injury.

Arm↗