Genomes and Genes
spinal muscular atrophies of childhood
Summary: A group of recessive inherited diseases that feature progressive muscular atrophy and hypotonia. They are classified as type I (Werdnig-Hoffman disease), type II (intermediate form), and type III (Kugelberg-Welander disease). Type I is fatal in infancy, type II has a late infantile onset and is associated with survival into the second or third decade. Type III has its onset in childhood, and is slowly progressive. (J Med Genet 1996 Apr:33(4):281-3)
- Soler Botija C, Ferrer I, Gich I, Baiget M, Tizzano E. Neuronal death is enhanced and begins during foetal development in type I spinal muscular atrophy spinal cord. Brain. 2002;125:1624-34 pubmed
- Hirayama K. [Juvenile muscular atrophy of unilateral upper extremity (Hirayama disease)--half-century progress and establishment since its discovery]. Brain Nerve. 2008;60:17-29 pubmed..There were fewer case reports from other countries than from Japan. As the number of patients is exceedingly large in Japan, there might be an ethnic factor in this disorder. ..
- Swoboda K, Kissel J, Crawford T, Bromberg M, Acsadi G, D Anjou G, et al. Perspectives on clinical trials in spinal muscular atrophy. J Child Neurol. 2007;22:957-66 pubmed..Following is an overview of the challenges and opportunities, current and future therapeutic strategies, and progress to date in clinical trials in spinal muscular atrophy. ..
- Xu X, Han H, Gao H, Hou C, Fan D, Fu Y, et al. The increased range of cervical flexed motion detected by radiographs in Hirayama disease. Eur J Radiol. 2011;78:82-6 pubmed publisher..Conventional flexion radiographs might be suitable to be used as first line radiographic examination, followed by MRI in cases of suspected Hirayama disease. ..
- Prior T, Swoboda K, Scott H, Hejmanowski A. Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2. Am J Med Genet A. 2004;130A:307-10 pubmed..Lastly, in cases similar to the ones described, the measurement of the SMN2 gene copy number may provide valuable prognostic information. ..
- Fujak A, Kopschina C, Gras F, Forst R, Forst J. Contractures of the upper extremities in spinal muscular atrophy type II. Descriptive clinical study with retrospective data collection. Ortop Traumatol Rehabil. 2010;12:410-9 pubmed..The findings of this study give us more information about the development of contractures of the upper extremities and aim to help to improve the quality of orthopaedic care of patients with SMA type II. ..
- Dressman D, Ahearn M, Yariz K, Basterrecha H, Martinez F, Palau F, et al. X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping. Genet Med. 2007;9:52-60 pubmed..The addition of new families and new markers has narrowed the disease gene interval for a XL-SMA locus between SNP FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3-Xq11.1). ..
- Andreassi C, Jarecki J, Zhou J, Coovert D, Monani U, Chen X, et al. Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients. Hum Mol Genet. 2001;10:2841-9 pubmed
- Sumner C, Huynh T, Markowitz J, Perhac J, Hill B, Coovert D, et al. Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Ann Neurol. 2003;54:647-54 pubmed..Valproic acid may increase SMN levels both by activating the SMN promoter and by preventing exon 7 skipping in SMN transcripts. Valproic acid and related compounds warrant further investigation as potential treatment for SMA. ..
- Fujak A, Kopschina C, Gras F, Forst R, Forst J. Contractures of the lower extremities in spinal muscular atrophy type II. Descriptive clinical study with retrospective data collection. Ortop Traumatol Rehabil. 2011;13:27-36 pubmed..The findings of this study give us more information about the development of contractures and deformities of the joints of the lower extremities and aim to help to improve the quality of orthopaedic care of patients with SMA type II. ..
- Chung B, Wong V, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics. 2004;114:e548-53 pubmed..With improvement in survival as a result of medical advances, assessment of the most current or the best-ever functional status at a designated age might be an important criterion for classification of SMA. ..
- Bach J, Vega J, Majors J, Friedman A. Spinal muscular atrophy type 1 quality of life. Am J Phys Med Rehabil. 2003;82:137-42 pubmed..80 +/- 1.75 controls, 5.27 +/- 1.14, < 0.001). Although there is a widespread perception that spinal muscular atrophy type 1 children have a poor quality of life, this perception is not shared by their care providers. ..
- Migita M, Uchikoba Y, Orimo H, Shimada T, Matsumoto T, Hayakawa J, et al. Genetic diagnosis of Werdnig-Hoffmann disease: a problem for application to prenatal diagnosis. J Nippon Med Sch. 2003;70:45-8 pubmed..Therefore, this method should be applied with great care to prenatal diagnosis using chorionic villi, which may be contaminated with maternal tissue. ..
- Sakai K, Ono K, Okamoto Y, Murakami H, Yamada M. Cervical flexion myelopathy in a patient showing apparent long tract signs: a severe form of Hirayama disease. Joint Bone Spine. 2011;78:316-8 pubmed publisher..Our patient's disease progression suggests that cervical flexion myelopathy patients with severe cervical cord compression in flexion may develop extensive cervical cord injury beyond the anterior horn. ..
- Bach J. The use of mechanical ventilation is appropriate in children with genetically proven spinal muscular atrophy type 1: the motion for. Paediatr Respir Rev. 2008;9:45-50; quiz 50; discussion 55-6 pubmed publisher..In conclusion, both non-invasive aids and tracheostomy can prolong survival for SMA 1 patients, and it should be left up to the family to decide which, if either, they would like to use. ..
- Tashiro K, Kikuchi S, Itoyama Y, Tokumaru Y, Sobue G, Mukai E, et al. Nationwide survey of juvenile muscular atrophy of distal upper extremity (Hirayama disease) in Japan. Amyotroph Lateral Scler. 2006;7:38-45 pubmed..There was a predominantly unilateral hand and forearm involvement with 'cold paresis'. The imaging findings are described. ..
- Zebala L, Bridwell K, Baldus C, Richards S, Dormans J, Lenke L, et al. Minimum 5-year radiographic results of long scoliosis fusion in juvenile spinal muscular atrophy patients: major curve progression after instrumented fusion. J Pediatr Orthop. 2011;31:480-8 pubmed publisher..The purpose of this study was to assess minimum 5-year radiographic outcomes, MCP, and factors for MCP after spinal surgery in juvenile SMA patients with open triradiate cartilage at the time of surgery...
- Watihayati M, Zabidi Hussin A, Tang T, Matsuo M, Nishio H, Zilfalil B. Deletion analyses of SMN1 and NAIP genes in Malaysian spinal muscular atrophy patients. Pediatr Int. 2007;49:11-4 pubmed..The lower percentage of the SMN1 gene deletion may be due to the possibility that the present study included some patients without SMN1 gene abnormality and/or some patients with non-deletion type mutations in the SMN1 gene. ..
- Savas S, Eraslan S, Kantarci S, Karaman B, Acarsoz D, Tukel T, et al. Prenatal prediction of childhood-onset spinal muscular atrophy (SMA) in Turkish families. Prenat Diagn. 2002;22:703-9 pubmed
- Ryan M. The use of invasive ventilation is appropriate in children with genetically proven spinal muscular atrophy type 1: the motion against. Paediatr Respir Rev. 2008;9:51-4; discussion 55-6 pubmed publisher..Prolongation of life by invasive ventilation in such cases is futile given the absence of curative treatments for infants with SMA1, and overly burdensome given the unacceptable quality of life of such children. ..
- Parsons D, McAndrew P, Monani U, Mendell J, Burghes A, Prior T. An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene. Hum Mol Genet. 1996;5:1727-32 pubmed..This mutation provides strong support for SMN as the SMA-determining gene and indicates that disruption of SMNT on its own is sufficient to produce a severe type I SMA phenotype. ..
- Tokumaru Y, Hirayama K. [Cervical collar therapy for juvenile muscular atrophy of distal upper extremity (Hirayama disease): results from 38 cases]. Rinsho Shinkeigaku. 2001;41:173-8 pubmed..Improvement is expected in patients who have shorter duration of illness and have mild cord atrophy in a neutral neck position. Early diagnosis and therapeutic intervention may minimize the functional disability of young patients. ..
- Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155-65 pubmed..These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene. ..
- Zerres K, Rudnik Schoneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa Petrusewicz I. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci. 1997;146:67-72 pubmed..The data provide a reliable basis of the natural history of proximal SMA and support a classification system that is based primarily on age at onset and the achievement of motor milestones. ..
- Granata C, Merlini L, Magni E, Marini M, Stagni S. Spinal muscular atrophy: natural history and orthopaedic treatment of scoliosis. Spine (Phila Pa 1976). 1989;14:760-2 pubmed..Data on characteristics of the scoliotic curve are reported. The effectiveness of orthopaedic treatment in the prevention of scoliosis is discussed. ..
- Phillips D, Roye D, Farcy J, Leet A, Shelton Y. Surgical treatment of scoliosis in a spinal muscular atrophy population. Spine (Phila Pa 1976). 1990;15:942-5 pubmed..The prolonged survival of patients with spinal muscular atrophy justifies aggressive orthopaedic management of scoliosis to prevent progression of deformity and improve sitting comfort. ..
- Brown J, Zeller J, Swank S, Furumasu J, Warath S. Surgical and functional results of spine fusion in spinal muscular atrophy. Spine (Phila Pa 1976). 1989;14:763-70 pubmed..Surgical patients never approached their preoperative skill levels. Therapy evaluations further demonstrated that there were no difference in function between either operative group. ..
- Nicot F, Hart N, Forin V, Boule M, Clement A, Polkey M, et al. Respiratory muscle testing: a valuable tool for children with neuromuscular disorders. Am J Respir Crit Care Med. 2006;174:67-74 pubmed..Simple volitional respiratory muscle tests constitute a valuable tool for the assessment of respiratory muscle strength in young patients with neuromuscular disorders. ..
- Lehman V, Luetmer P, Sorenson E, Carter R, Gupta V, Fletcher G, et al. Cervical spine MR imaging findings of patients with Hirayama disease in North America: a multisite study. AJNR Am J Neuroradiol. 2013;34:451-6 pubmed publisher..Findings are often present on neutral MR images and, in the appropriate clinical scenario, should prompt flexion MR imaging to evaluate anterior dural shift. ..
- Zheng C, Zhu Y, Zhu D, Lu F, Xia X, Jiang J, et al. Motor unit number estimation in the quantitative assessment of severity and progression of motor unit loss in Hirayama disease. Clin Neurophysiol. 2017;128:1008-1014 pubmed publisher..These results have provided evidence for the application of MUNE in estimating the reduction of motor unit in HD and confirming the validity of MUNE for tracking the progression of HD in a clinical setting. ..
- Rudnik SchÃ¶neborn S, BarisiÄ‡ N, Eggermann K, Ortiz BrÃ¼chle N, GrÄ‘an P, Zerres K. Distally pronounced infantile spinal muscular atrophy with severe axonal and demyelinating neuropathy associated with the S230L mutation of SMN1. Neuromuscul Disord. 2016;26:132-5 pubmed publisher..Our observations widen the phenotypic consequences of SMN1 gene mutations and support the notion to look for additional genetic factors which may modify the clinical picture in atypical cases. ..
- Hardart M, Truog R. Spinal muscular atrophy--type I. Arch Dis Child. 2003;88:848-50 pubmed
- Zhou B, Chen L, Fan D, Zhou D. Clinical features of Hirayama disease in mainland China. Amyotroph Lateral Scler. 2010;11:133-9 pubmed publisher..Hirayama disease is under-recognized in mainland China. ..
- Felker M, Garg B. Proximal muscle weakness in a 15-year-old boy. Semin Pediatr Neurol. 2008;15:186-9; discussion 189 pubmed publisher..We present a case of an adolescent boy with proximal weakness and a mildly elevated creatine kinase. He was found to have spinal muscular atrophy type III rather than a myopathy. ..
- Imajo Y, Kato Y, Kanchiku T, Suzuki H, Taguchi T. Pathology and prognosis of proximal-type cervical spondylotic amyotrophy: new assessment using compound muscle action potentials of deltoid and biceps brachii muscles. Spine (Phila Pa 1976). 2011;36:E476-81 pubmed publisher..These patients were able to fully recover function. ..
- Barois A, Mayer M, Desguerre I, Chabrol B, Berard C, Cuisset J, et al. [Spinal muscular atrophy. A 4-year prospective, multicenter, longitudinal study (168 cases)]. Bull Acad Natl Med. 2005;189:1181-98; discussion 1198-9 pubmed..The IFM may thus be useful as the main outcome measure during therapeutic trials. ..
- Lim Y, Koh I, Park Y, Kim J, Kim D, Kim H, et al. Exome sequencing identifies KIAA1377 and C5orf42 as susceptibility genes for monomelic amyotrophy. Neuromuscul Disord. 2012;22:394-400 pubmed publisher..4×10(-5), OR=61.69, 95% confidence interval=9.62-394.94, in case of combination of two heterozygotes). These data suggest that KIAA1377 and C5orf42 synergistically play a role as susceptibility genes for monomelic amyotrophy. ..
- Drake M, Cox P. Ethics: end-of-life decision-making in a pediatric patient with SMA type 2: the influence of the media. Neurology. 2012;78:e143-5 pubmed publisher..This difficult decision is influenced by confluence of parental, doctor, social, cultural, moral, religious, legal, and economic factors and more recently the media. ..
- Zeng J, Ke L, Deng X, Cai M, Tu X, Lan F. [Molecular diagnosis of spinal muscular atrophy by multiplex ligation-dependent probe amplification]. Zhonghua Yi Xue Za Zhi. 2008;88:3262-4 pubmed..01). Two of the 10 fetuses had homozygous deletion of SMN1. The MLPA technique has proved to be an accurate and reliable tool for the molecular diagnosis of SMA, both in patients and in healthy carriers. ..
- Fuller H, Shorrock H, Gillingwater T, Pigott A, Smith V, Kulshrestha R, et al. Two Cases of Spinal Muscular Atrophy Type II with Eosinophilic Oesophagitis. J Neuromuscul Dis. 2017;4:357-362 pubmed publisher..Given that there is a specific treatment strategy for EoE, these cases highlight the importance of considering this condition in clinical investigations - especially for patients with SMA - who have GOR, discomfort, and oral aversion...
- Hayashi M. Oxidative stress in developmental brain disorders. Neuropathology. 2009;29:1-8 pubmed publisher..These findings imply involvement of oxidative stress in developmental brain disorders; antioxidant agents could prove to be useful for treating patients with those disorders. ..
- Prieto Rodrigo M, Sànchez Montero F, Hernández Valero A, Blanco Blanco J, Muriel Villoria C. [Subarachnoid anesthesia in a patient with Kugelber-Welander-type spinal muscular atrophy]. Rev Esp Anestesiol Reanim. 2003;50:309-10 pubmed
- Liang Y, Chen X, Yu Z, Chen C, Bi S, Mao L, et al. Deletion analysis of SMN1 and NAIP genes in Southern Chinese children with spinal muscular atrophy. J Zhejiang Univ Sci B. 2009;10:29-34 pubmed publisher..The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA. ..
- Yang J, Kasat N, Suh S, Kim S. Improvement in reflux gastroesophagitis in a patient with spinal muscular atrophy after surgical correction of kyphoscoliosis: a case report. Clin Orthop Relat Res. 2011;469:3501-5 pubmed publisher..This patient illustrates the relationship between spinal deformity and gastrointestinal symptoms. Postural balance correction resulted in the alleviation of reflux gastroesophagitis symptoms secondary to hiatus hernia. ..
- Cutillo L, Pizziconi C, Tozzi A, Verrillo E, Testa M, Cutrera R. Predicted and measured resting energy expenditure in children with spinal muscular atrophy 2. J Pediatr. 2014;164:1228-30 pubmed publisher..In patients with spinal muscular atrophy type 2, measured REE was lower than predicted. We also found a correlation between energy consumption and motor skills. ..
- Yuan N, Wang C, Trela A, Albanese C. Laparoscopic Nissen fundoplication during gastrostomy tube placement and noninvasive ventilation may improve survival in type I and severe type II spinal muscular atrophy. J Child Neurol. 2007;22:727-31 pubmed
- Iannaccone S. Outcome measures for pediatric spinal muscular atrophy. Arch Neurol. 2002;59:1445-50 pubmed..The PedsQL Neuromuscular Module for parents had moderately high reliability. A tool for motor function may be more useful in clinical trials of childhood SMA than one for quantitative muscle strength. ..