Spastic paraplegia type 49 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) & the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure & complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and other problems with the nervous system. Spastic paraplegia type 49 is a complex hereditary spastic paraplegia.
Spastic paraplegia type 49 often begins with weak muscle tone (hypotonia) that starts in infancy. During childhood, spasticity & paraplegia develop & gradually worsen, causing difficulty walking and frequent falls. In addition, affected individuals have moderate to severe intellectual disability & distinctive physical features, including short stature; chubbiness; an unusually small head size (); a wide, short skull (); a short, ; and . Some people with spastic paraplegia type 49 develop seizures.
Problems with autonomic nerve cells (autonomic ), which control involuntary body functions such as heart rate, digestion, & breathing, result in several features of spastic paraplegia type 49. Affected individuals have difficulty feeding beginning in infancy. They experience a backflow of stomach acids into the esophagus (called or GERD), causing vomiting. GERD can also lead to recurrent bacterial lung infections called aspiration pneumonia, which can be life-threatening. In addition, people with spastic paraplegia type 49 have problems regulating their breathing, resulting in pauses in breathing (apnea), initially while sleeping but eventually also while awake. Their blood pressure, pulse rate, and body temperature are also irregular.
People with spastic paraplegia type 49 can develop recurrent episodes of severe weakness, hypotonia, & abnormal breathing, which can be life threatening. By early adulthood, some affected individuals need a machine to help them breathe (mechanical ventilation).
Other signs & symptoms of spastic paraplegia type 49 reflect problems with sensory neurons, which transmit information about sensations such as pain, temperature, & touch to the brain. Many affected individuals are less able to feel pain or temperature sensations than individuals in the general population. Affected individuals also have abnormal or absent reflexes (areflexia).
Because of the nervous system abnormalities that occur in spastic paraplegia type 49, it has been suggested that the condition also be classified as a hereditary sensory & autonomic neuropathy, which is a group of conditions that affect sensory & autonomic neurons.