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AUTUMN 2023 InTouch | 17 individuals usually experience mild to moderate muscle weakness, tremor, twitching, or mild breathing problems. Typically, only muscles close to the centre of the body (proximal muscles), such as the upper arms and legs, are affected in type 4 spinal muscular atrophy. Related Disorders There are numerous other genetic disorders resulting in the loss of motor neurons that are categorized separately from classic SMA due to distinct genetic changes that are not related to a deficiency in the production of SMN protein. These so-called non-5q spinal muscular atrophies have a broad range of phenotypes often preferentially affecting certain muscle groups (e.g., proximal, distal, bulbar) and may be associated with other extra-muscular symptoms. The non-5q SMAs should be considered when the diagnosis is otherwise uncertain. These include x-linked infantile SMA with arthrogryposis, SMA with respiratory distress type I (SMARD1), and other congenital distal SMAs. Diagnosis of SMA The diagnosis of spinal muscular atrophy (SMA) is established in individuals with the following: • A history of motor difficulties • Evidence of motor unit disease on physical examination • Mutation detected in the SMN1 gene. Genetics of SMA SMA is caused by a mutation in the SMN1 gene located on the q arm of chromosome 5. Humans possess two copies of the SMN1 gene, one from each parent. SMA results when both SPINAL MUSCULAR ATROPHY copies are defective. This specific type of inheritance is called recessive. Each parent has one functional gene which is sufficient to avoid symptoms. Each parent is known as a carrier. Two carrier parents have a 1 in 4 chance (25%) in each pregnancy of having a child affected with the condition. In SMA approximately 2% of people with the condition have a new defect in one of their genes. In this situation, only one parent is a carrier, and the other defect occurs randomly within the individual. This is called a de novo mutation (new and not inherited). The SMN1 gene provides instructions for making survival motor neuron (SMN) protein, which is necessary for maintaining motor neurons. individual with SMA has, the milder the symptoms because the increased amount of SMN protein produced by extra copies of the less efficient gene has a protective effect. This explains the phenotypic spectrum of the disease. Most children with SMA type 1 only have 1 or 2 copies of SMN2, while those with SMA type 4 might have 3 to 4 copies. Genetic counseling is available to families who have had a diagnosis of SMA. This service provides information, helps families understand inheritance patterns and what this means in their family, and enables people to make more informed family-planning decisions. When muscle fibres are no longer being stimulated, they degenerate. The result is muscle atrophy and weakness. However, humans also possess a variable number of copies of a similar gene called SMN2. Without sufficient SMN protein, the motor neurons die and thus can no longer send signals to muscle fibres. When muscle fibres are no longer being stimulated, they degenerate. The result is muscle atrophy and weakness. However, humans also possess a variable number of copies of a similar gene called SMN2. The SMN2 gene can also produce SMN protein. However, SMN2 is lacking an important sequence called exon 7. This difference results in the production of less functional, unstable SMN protein. Even so, the SMN2 gene can partially compensate for the disease by producing a small percentage of functional protein. The more copies of SMN2 an Management of SMA Supportive therapy Because poor weight gain, sleep difficulties, pneumonia, scoliosis, and joint contractures are common features of SMA, supportive management revolves around treatment of the different presentations of these. When nutrition and risk of aspiration are a concern in SMA, placement of a gastrostomy tube is appropriate. As respiratory function deteriorates, tracheotomy or noninvasive respiratory support is offered. Respiratory secretion clearance techniques may involve manual or Continued over ...