Fragile X syndrome (FXS) is a genetic condition that causes intellectual disability, behavioral and learning challenges, various physical characteristics and, in some cases, seizures. Though FXS occurs in both genders, males are more significantly affected than females, and generally with greater severity. It is also the leading known genetic cause of autism.
FXS is the most common cause of inherited intellectual disability and most common known genetic cause of autism which affects 1 in 68 children in the United States. It is estimated more than 40% of all children with FXS are also diagnosed with autism. Of children diagnosed with an Autism Spectrum Disorder, roughly 5% have FXS as well. The full mutation, those with FXS, appears in approximately 1 in 3600 to 4000 males and 1 in 4000 to 6000 females. The premutation occurs in about 1 in 151 females and 1 in 468 males. Those who carry this premutation, also referred to as “carriers”, have a high chance of passing either the full mutation or the premutation to their offspring. More than 1.3 million Americans have or are at risk of developing FXS or a related carrier disorders.
The majority of males with FXS have a significant intellectual disability. The spectrum ranges from subtle learning disabilities to severe intellectual disability and autism. Behavioral characteristics include attention deficit disorders, speech disturbances, hand biting, hand flapping, poor eye contact, and aversion to touch and noise. There are various physical characteristics which may also be be present: large ears, long face, macroorchidism, connective tissue issues and hyper-flexible joints, to name a few. While some females with FXS will exhibit these characteristics, fewer females are affected and their degree of impact is usually diminished.
Because Fragile X presents itself in such a myriad of ways, it is often challenging for families to get a clear diagnosis of the disorder. In fact, it is thought that a high percentage of those affected with FXS are undiagnosed or misdiagnosed.
The condition is caused by abnormalities in a specific gene on the X chromosome, a strand of DNA that carries hereditary information.
Children with FXS don’t produce enough of a certain protein known as the Fragile X Mental Retardation 1 (FMR1) protein, causing cognitive and behavioral impairments. Females are less affected than males because females have two X chromosomes (while males have one X and one Y). Males with Fragile X only have the nonfunctioning gene while females with Fragile X have one normally functioning gene which partially compensates for the nonfunctioning gene.
Men with the premutation will pass the altered gene to all of their daughters and none of their sons. Women with the premutation have a 50% chance of passing the altered gene to all of their offspring.
Special education, speech and language therapy, occupational therapy and behavioral therapies help to address many of the behavioral, and cognitive impacts of Fragile X Syndrome. Medical intervention can help with aggression, anxiety, hyperactivity and poor attention span. These interventions treat the symptoms as currently, there is no fully effective treatment for Fragile X Syndrome. However, clinical trials are proving to be successful and a Fragile X Syndrome “cure” is on the horizon.