SpineSpinal muscular atrophy: Classification, aetiology, and treatment of spinal deformity in children and adolescents☆
Introduction
Spinal muscular atrophy (SMA) is an uncommon hereditary condition of autosomal recessive inheritance, which affects the anterior horn cells of the spinal cord and the neurons of the lower bulbar nuclei. It manifests clinically with symmetrical limb and trunk weakness affecting the proximal more than the distal trunk muscles and the lower more than the upper limbs. Sensation and mental function are not impaired.1 Fasciculation of the tongue and the deltoid are often seen, as well as a fine tremor affecting the hands.2, 3 This tremor resolves during relaxation or sleep. The development of scoliosis, joint contractures and dislocation of the hip are the most common orthopaedic problems associated with the condition. The natural history of SMA is premature death, which is caused by respiratory failure as the consequence of a gradually deteriorating respiratory muscular function.
The purpose of this article is twofold. Firstly, to provide a comprehensive overview on SMA, which is helpful to orthopaedists involved in caring for these children, including recent advancements in classification, understanding of the aetiology, and principles of management of the condition. The focus of the paper is, however, to investigate the characteristics of spinal deformity that develops in this group of patients and to describe a strategy for treatment. We believe that it is important to increase awareness of the complexity of these deformities in regard to their specific surgical considerations, as well as the coexistence of a multitude of associated medical problems that occur in this particular patient population and can jeopardize an inherently challenging surgical procedure.
Section snippets
Classification
There is no universally accepted classification for SMA. Currently, there is more than one classification systems in use with each one of these systems applying different terms to the various types of the condition (Table 1). A recent attempt at resolving this problem by the international SMA collaboration has led to the definition of specific diagnostic criteria and the development of a new classification system, which is based on the age at presentation of symptoms, functional abilities and
Epidemiology
Pearn et al.11 reported an incidence of 1 in 25,000 live births for SMA type I in the United Kingdom, making it one of the most common causes of genetically determined neonatal death. This translates to a gene frequency of about 1 in 160 and a carrier frequency of 1 in 80.12 Epidemiological data from Canada, Finland, Hungary, and Norway have recorded an incidence of SMA type I ranging from 1 in 25,000 to 1 in 15,000 live births.13, 14, 15, 16 The incidence in types II and III SMA account for
Aetiology and pathogenesis
The complete pathogenesis of SMA is still undetermined; however, the genetic cause of many cases has been attributed to two genes. The identification of the Survival of Motor Neuron 1 (SMN1 or telomeric SMNT) gene on the long arm of chromosome 5 (5q11.2–13.3) was first described by Brzustowicz et al. in 1990.21 The SMN1 gene lies within an inverted duplication which contains an almost identical copy of the gene (labelled SMN2 or centromeric SMNC).22 The majority of SMA patients (98.7%) with the
Diagnosis
The diagnosis of SMA is primarily based on the clinical features and can also be supported by a positive family history. The diagnostic criteria for the condition have been described by an international SMA collaboration (Table 2).4 The diagnostic studies include muscle and nerve biopsy, electromyography, and conduction velocity.
Muscle biopsy can be used to assist diagnosis and should be performed on moderately affected muscles using an open technique. A careful, atraumatic surgical technique
Orthopaedic problems
Orthopaedic manifestations of the condition that may require treatment can occur primarily in patients with SMA type II or III who have a longer life expectancy. Scoliosis and hip subluxation or dislocation are the two most common orthopaedic problems encountered. In the study by Evans et al.9 scoliosis affected all patients with moderate to severe disease. Progressive hip subluxation and dislocation occurred in up to 50% of patients with more severe disease often after the age of 5 years.9
Hip
Spinal deformity
Epidemiology: Spinal deformity in patients with SMA who survive early childhood constitutes a particularly common problem. There have been several previous studies to calculate the incidence of deformities of the spine in this group of patients.9, 37, 46, 47, 48, 49, 50 However, it is not likely that these studies have included the whole population of patients affected with SMA. A large number of children with SMA type I do not survive long enough for orthopaedic problems to require treatment
Treatment of patients with SMA
The treatment of SMA focuses on the prevention and management of medical complications, most commonly associated with poor respiratory function, and early interventions to correct musculoskeletal deformities in children with a favourable life expectancy. Despite the recent advances in our understanding of the genetic basis of SMA it remains difficult to predict which children that develop SMA at a young age will survive long enough to necessitate orthopaedic treatment. However, due to
Conservative management
There is no non-operative measure that has a documented effect on preventing scoliosis progression or the final outcome of the spinal deformity in children with SMA. The goal of all conservative modalities is not to correct the deformity but instead to retain function as the curve continues to progress and delay surgery for a later stage.
Seating support: Appropriate seating adaptations should be considered as the cornerstone of managing patients with scoliosis before surgical correction is
Conclusions
The development of spinal deformity constitutes the most common musculoskeletal problem in SMA and should be anticipated in almost all the patients who survive beyond early childhood. The development of an abnormal spinal curvature in this group of severely disabled children decreases their sitting tolerance, creates pain from impingement of the ribs against the pelvis, and accelerates deterioration in respiratory function. Scoliosis surgery in paediatric patients with SMA who have severe
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Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study
2022, Neuromuscular DisordersCitation Excerpt :Significant differences have been observed concerning the loss of walking ability in those with an onset of weakness before and after 3 years of age (SMA type IIIa and IIIb, respectively). Approximately 95–98% of SMA cases, irrespective of type, harbor a homozygous deletion of the ubiquitously expressed telomeric survival motor neuron (SMN) 1 gene on chromosome 5q13 [5–7], and are thus dependent on their SMN2 gene for SMN protein encoding [8]. Therefore, SMN2 copy number is the primary determinant of SMA severity and SMN2 copy count correlates inversely with disease severity [2,5,6,9,10].
Neuromuscular disorders: a guide for the orthopaedic surgeon
2019, Orthopaedics and TraumaCitation Excerpt :SMN1 produces 90% of the functional survival motor neurone protein whilst SMN2 only produces 10% of the functional protein. In SMA, individuals lack SMN1 hence it is the copy number of SMN2, to a large extent, that correlates with the clinical phenotype and level of weakness and disability.6,7 SMA type 1 is the commonest cause of death in infants from an inherited disorder and has an incidence of 1 in 10,000.
Scoliosis and the Impact in Neuromuscular Disease
2015, Paediatric Respiratory ReviewsCitation Excerpt :In these patients there is often bilateral caudal rib rotation of the more superior ribs that produces a narrow superior chest and a typical triangular shaped chest with preservation of the lower chest contour due to the incompressible abdominal contents. In patients with SMA-1 who survive past infancy and are positioned in a semi-upright position because of their lack of truncal support [3] their thorax will bend in one direction and they will develop scoliosis [7]. In broad longitudinal reviews of patients with SMA-2, the onset of scoliosis has been reported as early as 4 years of age [2] and progressed at annual rates of between 5° and 15° per year [2].
Observational study of caloric and nutrient intake, bone density, and body composition in infants and children with spinal muscular atrophy type I
2012, Neuromuscular DisordersCitation Excerpt :Spinal muscular atrophy (SMA) is one of the most common lethal recessive genetic diseases, with an incidence of 1 in 10,000 births [1,2].
Patients With Spinal Muscular Atrophy Use High Percentages of Trunk Muscle Capacity to Perform Seated Tasks
2019, American Journal of Physical Medicine and Rehabilitation
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The authors did not receive grants or outside funding in support of the preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution or other charitable or nonprofit organization with which the authors are affiliated or associated.