Many infants and young children with Fragile X have no distinctive physical features. Some children have very soft, velvety skin, a broad forehead, or a slightly larger head than other children their age.
However, when these children enter puberty, usually around age 11, they may begin to develop certain features that are typical of teens and adults with Fragile X, such as a longer face or jaw and larger, more noticeable ears. Most do not grow as tall as their peers, or as tall as one might expect them to grow, based on the height of their family members.
Other physical changes also come with puberty for those who have Fragile X. Many males develop enlarged testicles, a condition called macro-orchidism (pronounced mack-roe-ORK-id-izm). With this condition, the testicles may grow to twice their normal size. This condition is not due to hormonal imbalance and does not affect sexual development.
One job of FMRP may be to help the body maintain its connective tissues. Connective tissues support the body, inside and out. Many people with Fragile X have loose, flexible joints. They may have flat feet and be able to extend joints like the thumb, knee, and elbow further than normal. Weak connective tissue can predispose a person to certain medical conditions, such as hernia and frequent middle ear infections. Weak connective tissue can also affect the valves and vessels of the heart, so that blood in the heart may not flow smoothly, which creates a heart murmur (called mitral valve prolapse, pronounced my-trell valv proh lapss). Although it involves the heart, this condition is usually not life threatening, but it is a good idea for a person with a heart murmur to be monitored by a health care professional on a regular basis.
Late in life, some males who have a premutation may develop hand tremors 10 and problems with walking.
How does Fragile X affect the brain?
Understanding how Fragile X affects the brain and learning what role FMRP plays in normal brain development and function are areas of active research. For instance, some evidence suggests that FMRP is involved in forming pathways in the brain.
Normally, brain cells called neurons have special areas that grow toward each other to form connections. These connections, called “synapses,” are arranged in neural pathways. Thoughts, sounds, and memories are recorded and stored in these pathways. However, not every experience recorded in these neural pathways is useful or needs to be kept throughout life. So, as part of normal development, the brain “prunes” itself. Like pruning the branches of a tree, removing unneeded or ineffective pathways in the brain strengthens other pathways and makes room for new growth and new learning.
FMRP may somehow influence the pruning process in the brain. People without enough FMRP may have may have too many neural pathways or many connections that don’t work well. This situation would explain some of the symptoms of Fragile X, such as an extreme sensitivity to new sights, sounds, smells, and touches.
Using mice and fruit flies that no longer have a working gene to make FMRP, scientists are working to understand how the absence of this protein affects the brain. Recent research is trying to determine whether a certain process that runs out of control in mice with little or no FMRP leads to the behavioral and learning problems typical in people with Fragile X. Such animal studies may reveal exactly how FMRP functions in the brain and suggest ways to correct situations caused by a lack of the protein.
Fragile X affects females in some different ways. About 16 percent 11 to 19 percent 12 of females who have a premutation gene experience premature ovarian failure (POF), meaning their ovarian function stops before normal menopause, sometimes well before the age of 40. Some may experience POF as early as their mid-twenties. POF affects a woman’s ability to get pregnant. It is important, then, for women to know whether or not they have a premutation gene, and to have this knowledge early enough, so that they can consider their options for having a family. In contrast, POF occurs in only 1 percent of women who have two normal FMR1 genes, 13 and the average age of menopause for women who are not affected by Fragile X is 51. Women who have a full mutation gene do not lose ovarian function as early as women with a premutation gene, but they still tend to begin menopause earlier than women who are not affected by Fragile X. Scientists do not know why the effect is milder in women who have a full mutation form of the gene than in women with a premutation form of the gene.