Spinal Muscular Atrophy Health Article

Definition

Spinal muscular atrophies (SMAs) are a wide group of genetic disorders characterized by primary degeneration of anterior horn cells of the spinal cord, resulting in progressive muscle weakness. The most common form of spinal muscular atrophy is childhood proximal SMA. Other forms of SMAs include X-linked recessively inherited bulbospinal SMA, distal SMAs, scapuloperoneal SMAs, and others such as facioscapulohumeral, scapulohumeral, oculopharyngeal, and Ryukyuan SMAs.

Description

SMAs present with diverse symptoms and differ in age of onset, mode of inheritance, distribution of muscle weakness, and progression of symptoms.

Childhood proximal SMA is subdivided into three clinical groups: type I, type II, and type III SMA. SMA type IV designates adult form of proximal SMA. Although it is now apparent that the phenotype of SMA associated with mutations of the survival motor neuron (SMN1) gene spans a continuum without a clear delineation of subtypes, the classification is useful for prognosis and management.

SMA I (acute infantile SMA, Werdnig-Hoffman disease) manifests by decreased fetal movements in the last trimester of pregnancy in about one third of cases. About 65% of affected infants are floppy at birth, while delayed motor milestones are characteristic in all affected children by the age of six months. In addition to muscle weakness, clinical features include head lag, poor sucking and swallowing, weak cry, proximal limb weakness, and lack of reflexes. Affected children never raise their head, roll over, or walk. Sometimes weakness of the face and jaw muscles, finger tremor, and respiratory difficulty occur. Orthopedic abnormalities such as congenital dislocation of the hip, chest wall asymmetries, and flexion contractures are present in 25% of affected newborns.

SMA II (intermediate SMA) usually manifests itself between six and 12 months of age. Although poor muscle tone may be evident at birth or within the first few months of life, patients with SMA II may gain motor milestones slowly. Eighty percent are able to sit independently, although they are not able stand or walk alone. Limb girdle weakness, twitching, lack of reflexes, and weakness of tongue, face, and neck muscles are seen. Tremors affecting the upper extremities, musculoskeletal deformities, and respiratory failure occur.

SMA III (chronic SMA, Kugelberg-Welander disease) presents with the onset of symptoms after the age of 18 months. Patients walk independently, but may fall frequently or have trouble walking up and down stairs between age two to three years. Muscular weakness is present on both sides of the body, and the legs are more severely affected than the arms. Difficulty swallowing and difficulty speaking may occur in later stages of the disorder.

SMA IV manifests as muscle weakness usually in the second or third decade of life. The findings are similar to those described for SMA III.

Bulbospinal muscular atrophy (Kennedy disease) manifests as muscle weakness between the ages of 20 and 40 years. Weakness and atrophy in the lower extremities are usually followed by problems with the pectoral girdle, facial muscles, distal limb, and bulbar muscles. Muscle cramps on exertion often precede the weakness by several years. Fine tremors of the face are present in over 90% of patients. Type 2 diabetes mellitus, hand tremor, and infertility can also occur. Bulbar involvement predisposes the person with spinal muscular atrophy to recurrent aspiration pneumonia, due to weakening of the muscles necessary for efficient swallowing.

Other less common forms of SMAs include distal SMAs (10% of all SMA cases) and scapuloperoneal SMA (7% of all SMA cases). Distal SMAs are a group of disorders that manifest most commonly soon after birth, with muscle wasting in the hands and feet. Later in life, abnormal gait and foot deformities are seen. Similar clinical signs occur in adult-onset forms. Scapuloperoneal SMA has a characteristic pattern of muscle weakness, usually involving the heart and sensory neuropathy (Davidenkow's syndrome).