Motor neuron diseases are a group of rare diseases affecting spinal motor neurons. They clinically present with progressive degenerative muscle weakness and wasting and lead to impairment in mobility, speech, swallowing, and breathing functions. Spinal muscular atrophy (SMA) is the leading cause for motor neuron disease in children. Here, we focus on SMAs, including the most common SMA, also known as proximal or 5q-SMA, as well as atypical SMA, also known as SMA plus, especially riboflavin-responsive motor neuron disease, which is a treatable childhood-onset motor neuron disease.
ESSENTIALS OF DIAGNOSIS AND TYPICAL FEATURES
A diverse group of genetic disorders associated with spinal motor neuron loss
The most common form of SMA is 5q-SMA (also called proximal SMA), which is caused by homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene
Clinically presents with muscle weakness, with onset of symptoms ranging from the prenatal period to adulthood
Multisystem involvement; progressive weakening of respiratory and swallow muscles leads to respiratory insufficiency and feeding intolerance
Genetic testing is essential for establishing diagnosis
Genetic modification treatments are now available for 5q-SMA
SMAs are a group of degenerative neurologic diseases affecting spinal motor neurons caused by genetic mutations in a group of genes. The most common form of SMA is 5q-SMA (also called proximal SMA), which is caused by homozygous deletion or mutation of the SMN1 gene. It accounts for up to 95% of SMA cases. Besides the clinical features, genetic analyses are essential to establish the diagnosis. Management is provided by a multidisciplinary neuromuscular team. Various genetic modification medications are now available for patients with 5q-SMA (eg, nusinersen and risdiplam for gene transcription modification treatment and onasemnogene abeparvovec-xioi for gene delivery therapy).
For 5q-SMA, symptom onset varies from the prenatal period to adulthood. Patients present with symptoms of progressive proximal muscle weakness. Traditionally, 5q-SMA has been classified into types 1 to 3. Type 1 patients clinically present with symptoms beginning after birth and before age 6 months; affected patients have generalized hypotonia and are unable to sit independently. Breathing and swallowing functions are affected, and patients need breathing and feeding support to survive. Type 1 patients typically die before 2 years of age. Type 2 patients have symptoms that begin between 6 and 18 months. They achieve the ability to sit usually by 9 months but are never able to stand or walk. Type 3 patients present with symptom onset between 18 months and adulthood. Standing or walking without support is achieved, although many lose these abilities later in life with disease progression. Muscle weakness is more proximal and affects the lower extremities more than the upper extremities. Deep tendon reflexes are usually depressed or absent. Hand tremor can be seen in type 2 and 3 patients. Tongue atrophy with ...