RAI1, is responsible for most of the features of the condition. In most of these cases, the deletion is not inherited, occurring randomly during the formation of eggs or sperm, or in early fetal development. In rare cases, the deletion is due to a chromosomal balanced translocation in one of the parents. In about 10% of cases, SMS is caused by a mutation in the RAI1 gene. These mutations may occur randomly, or may be inherited from a parent in an autosomal dominant manner. Treatment for SMS depends on the symptoms present in each person.

Facial features in people with SMS may be subtle in early childhood, but usually become more apparent with age. They may include:

• A broad, square-shaped face with deep-set eyes, full cheeks, and a prominent lower jaw
• A "flattened" appearance to the middle of the face and the bridge of the nose
• A downward-turned mouth with a full, outward-curving upper lip

While people with SMS often have affectionate, engaging personalities, most also have behavioral problems. These may include:

• Frequent temper tantrums and outbursts
• Aggression
• Anxiety
• Impulsiveness
• Difficulty paying attention
• Self-injury, including biting, hitting, head-banging, and skin picking
• Repetitive self-hugging (a trait that may be unique to SMS)
• Compulsively licking the fingers and flipping pages of books (a behavior known as 'lick and flip')

Additional features of SMS may include short stature, scoliosis, reduced sensitivity to pain and temperature, chronic ear infections, obesity, and a hoarse voice.

RAI1 gene is responsible for most of the features of SMS. The loss of other genes in the deleted region may explain why the features may vary from person to person.

About 10% of people with SMS have a mutation in the RAI1 gene (not a deletion of the larger part of the chromosome). Although people with an RAI1 mutation have many of the major features of SMS, they are less likely to have short stature, hearing loss, and heart or kidney abnormalities.RAI1 gene mutations may occur randomly, or they may be inherited from a parent in an autosomal dominant manner.

In a very small number of cases, SMS in a child can result from a parent having a balanced translocation (resulting in a deletion in the child), or from a mutation in the RAI1 gene that was inherited from a parent. Very rarely, parental germline mosaicism has been reported to cause SMS in a child.

Because there are cases in which SMS may be inherited, genetic testing is recommended for parents of children who are diagnosed with SMS. Information from parental testing can help determine if there are risks to other family members.