Key Facial Characteristics
NOT always present
- Long, narrow face
- Large, everted ears
- Macrocephaly
- Prominent jaw and forehead
Fragile X Syndrome
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Genetics
- Key inherited cause of intellectual disability and autism
- Down syndrome is the most common inherited cause of intellectual disability, alone (ie, without autism).
- Fragile X syndrome is the most common single gene (monogenic) cause of autism
- Fragile X syndrome is a trinucleotide (CGG) repeat disorder
- Normal CGG repeat length: 5 – 40 repeats
- Premutation: 55 to 200 repeats (can cause premature ovarian failure or Fragile X-associated tremor/ataxia syndrome)
- Full mutation: > 200 repeats
- FMR1 gene mutation (abnormal FMRP protein) on the X chromosome
- Affects protein production and synaptic connections for relaying of nerve impulses
- The less FMRP protein produced (ie, the more severe the gene mutation), the more severe the clinical effects (cognitive, social, etc…)
- X-linked dominant pattern of inheritance
- Can affect both girls and boys BUT boys are more severely affected
Typical dysmorphic features and other clinical characteristics
- Long, narrow face
- Large, everted ears
- Macrocephaly
- Prominent jaw and forehead
- Testicular enlargement (macroorchidism)
- Connective tissue abnormalities
- Hyper-flexible joints
- Seizures occur in 15-20% of patients
Cognitive Impairment
- Autism occurs in 1/3 of patients
- 10% of children are nonverbal
- Moderate intellectual disability
- More severe and more common in males
Behavioral Abnormalities
- Autism
- Attention deficit hyperactivity disorder
- Impulsivity, fidgeting, hand-biting or flapping
References
- Fragile X syndrome, https://ghr.nlm.nih.gov/condition/fragile-x-syndrome
- Hagerman, R.J., Berry-Kravis, E., Hazlett, H.C., Bailey, D.B., Moine, H., Kooy, R.F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J.L., et al. (2017). Fragile X syndrome. Nat. Rev. Dis. Primer 3, 17065.
- Rajaratnam, A., Shergill, J., Salcedo-Arellano, M., Saldarriaga, W., Duan, X., and Hagerman, R. (2017). Fragile X syndrome and fragile X-associated disorders. F1000Research 6.
Image Reference
- Modified from “Fragile X Syndrome.” Wikipedia, May 22, 2018. https://en.wikipedia.org/w/index.php?title=Fragile_X_syndrome&oldid=842384990.