The cause of Rubinstein-Taybi syndrome is presently unknown. There is no current research to support a chromosomal abnormality or environmental exposures (e.g., to polluted air or water, alcohol, drugs or cigarettes) as a source. Cases of Rubinstein-Taybi syndrome are sporadic and random.

There are no medical tests used to identify Rubinstein-Taybi syndrome. Instead, it is generally identified by a pediatrician or a geneticist based on characteristic physical and behavioral features, which are described below. The telltale features are not necessarily present from birth, and therefore may go unnoticed for months or even years. For example, individuals who have the condition are commonly short in stature, but this is not apparent at birth. The babies are usually born average in weight and height but fail to grow at a normal rate. The delay in the growth rate continues into adolescence.

Facial features common to Rubinstein-Taybi syndrome include eyes that are space widely apart, a wide nasal bridge, and a pronounced nose. The head and the lower jaw are usually smaller than average in size. The eyes slant downward and the eyelids are droopy. The eyes tend to cross and the palate often has a high arch. Hair tends to be thick and low-lying on the brow. Rubinstein-Taybi children also tend to have broad thumbs and broad first toes.

Individuals with Rubinstein-Taybi syndrome may have skeletal abnormalities. They typically fail to achieve developmental milestones involving gross motor skills. Coordination and balance are negatively affected by the condition. Affected children often have difficulty breathing and/or swallowing. Rubinstein-Taybi syndrome children tend to be happy and amiable. They sometimes engage in self-stimulatory behaviors like rocking or spinning in circles, but this is not the norm among the population. They are rarely treated for hyperactivity, even though short attention span can be a significant problem.