The overall prevalence of MSA is estimated at 4.6 cases per 100,000 people.[4]
MSA is characterized by a combination of the following:[5]

• autonomic dysfunction
• parkinsonism (muscle rigidity +/ tremor and slow movement)
• ataxia (Poor coordination / unsteady walking)

These can present in any combination,[6] making the phrase "multiple system atrophy" of limited use in specifying the condition of an individual patient.

When autonomic failure predominates, the term Shy-Drager syndrome is often used, although this term is no longer current, given the recent terminology changes which are explained below.[7] This syndrome was named after Dr Milton Shy and Dr Glenn Drager, who identified it in 1960, but the American Autonomic Society and the American Academy of Neurology redefined it as multiple system atrophy with autonomic phenomena in 1996.[8][9][10] The name "Shy-Drager syndrome" is still used occasionally for multiple system atrophy when the primary symptoms are autonomic failure.

A variant with combined features of MSA and Lewy body dementia may also exist. [11]

The most common first sign of MSA is the appearance of an "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling Parkinson's disease) found in 62% at first presentation. Other common signs at onset include problems with balance (found in 22%), followed by genito-urinary problems (9%). For men, the first sign can be erectile dysfunction (unable to achieve or sustain an erection). Both men and women often experience problems with their bladders including urgency, frequency, incomplete bladder emptying or an inability to pass urine (retention). About 1 in 5 MSA patients will suffer a fall in their first year of disease.[3]

As the disease progresses three groups of symptoms predominate. These are:
1. Parkinsonism (slow, stiff movement, writing becomes small and spidery)
2. Cerebellar dysfunction (difficulty coordinating movement and balance)
3. Autonomic dysfunction (impaired automatic body functions) including:
• postural or orthostatic hypotension, resulting in dizziness or fainting upon standing up
• urinary incontinence
• impotence
• constipation
• dry mouth and skin
• trouble regulating body temperature due to abnormal sweating
• abnormal breathing during sleep
Other symptoms such as double vision[12] can occur. Not all patients experience all of these symptoms.