Fragile X comes from a short genetic stutter that grows across generations
Most people carry somewhere between 5 and 40 copies of a three-letter DNA sequence, CGG, in a gene called FMR1. Push that count past 200 and the gene shuts down. The result is fragile X syndrome, the most common inherited cause of intellectual disability and the leading single-gene cause of autism.
The FMR1 gene sits on the X chromosome and makes a protein, FMRP, that neurons need to build proper connections with one another. When the CGG repeat balloons, the cell chemically tags that stretch of DNA with methyl groups and silences it, so the protein goes missing. Counts between 55 and 200 form an in-between state called a premutation. Carriers usually escape the full syndrome, but women carrying one face a higher chance of having an affected child, and roughly half of male carriers over seventy develop a slowly progressing tremor and loss of coordination.
Sex makes a large difference. A male with the full mutation has one X chromosome and almost always shows the condition; a female has a second, working copy, and only about half of those with a full mutation are noticeably affected. Average measured IQ for males falls below 55, while affected females mostly land between about 70 and 85. The condition occurs in an estimated 1 in 4,000 people.
The profile is distinctive. Physical signs can include a long face, prominent ears, very flexible joints, soft skin and, after puberty, enlarged testicles. Verbal skills tend to hold up better than working memory, spatial reasoning and mathematics. Hyperactivity is common, peaking before school age, and seizures affect a minority. Around a third show autistic traits.
One of the most striking features is social. People with fragile X often want company and show more empathy than groups with other causes of intellectual disability, yet unfamiliar faces and places can trigger intense shyness, averted gaze and anxiety; in one series up to three quarters of males were described as excessively shy. Part of that may stem from difficulty recognising faces seen before. Repetitive habits such as hand-flapping or returning to a favourite topic are common but, unlike obsessive-compulsive rituals, tend to be enjoyed. There is no cure or approved drug for the condition itself, and diagnosis rests on a genetic test that counts the repeats.
Source: Fragile X syndrome
