Behavioral Features. Hyperactivity. Autism. Females

A. Hyperactivity. Behavior problems are commonly seen in fragile X males and affected females. The majority of young fragile X males demonstrate hyperactivity and a short attention span; they have difficulty in focusing their attention on a single task. Their attention will impulsively shift from one topic or object to another and this is usually associated with an increased activity level.

Their impulsivity can also be seen in their language, which is characterized by poor topic maintenance and a cluttering of thoughts and ideas that can be communicated in a rapid and sometimes incomprehensible way. Often the diagnosis is made when the child is evaluated for hyperactivity or language delay, which is noted after 2 years of age. Younger fragile X boys may also demonstrate hypotonia or poor muscle tone in addition to their hyperextensible joints.

B. Autism. Other unusual features are commonly seen with hyperactivity and have been described as autistic-like. These features include poor eye contact, shyness or social interactional problems, hand-flapping when they are excited or angry, and other hand stereotypies or unusual hand movements. Obsessive and compulsive behavior, sometimes ritualistic behavior, can be seen and repetition or perseveration in both behavior and language are very common. Often a child will do an activity over and over again in a compulsive fashion or will speak in repetitive phrases. Other autistic features include tactile defensiveness or sensitivity or aversion to touch, overreactions to minimal stimuli, and frequent tantrums. Hand-biting is seen in the majority of young fragile X males and may persist into adulthood, causing calluses on the finger where repetitive biting occurs.

Although the majority of young fragile X males demonstrate autistic features, a full diagnosis of infantile autism or autistic disorder is seen only in approximately 16% of fragile X males. This diagnosis is made only when a pervasive lack of relatedness and lack of interest in social interactions exist. The majority of fragile X boys are friendly and yet autistic-like features interfere with normal relatedness.

Populations of autistic males have been screened for fragile X syndrome and it has been detected by cytogenetic studies in approximately 7% of autistic males. Fragile X syndrome therefore represents the most common inherited cause of autism that can be identified. The fragile X syndrome is also responsible for 30 to 50% of all forms of X-linked mental retardation. In institutional screening studies of retarded individuals, fragile X syndrome has been identified in 1 to 10% of various populations that have been studied.

If one evaluates children or adults who are retarded for unknown reasons, fragile X can be detected in 2 to 10% of these individuals. Therefore, any child or adult who presents with mental retardation or autism of unknown etiology should be tested for fragile X by performing DNA studies or cytogenetic studies on a peripheral blood sample using appropriate tissue culture conditions. Although the yield of fragile X positive individuals may be approximately 2 to 10%, this is a very significant yield in the evaluation of children or adults with developmental disabilities.

C. Females. Females who are affected with fragile X syndrome with either learning disabilities or mild mental retardation often demonstrate attentional problems with distractibility but usually without significant hyperactivity. Although they occasionally demonstrate some autistic features such as hand-flapping or hand-biting, they more commonly demonstrate shyness and social withdrawal. The shyness can be profound, particularly in adolescence, and feelings of social isolation leading to depression are quite common. Depression is also a finding that is frequently seen in mothers of fragile X children. It is unclear whether this finding is related to the environmental stresses of raising a difficult child with fragile X syndrome, or whether the fragile X mutation when present just in the carrier state can predispose an individual to depression.