Fragile X syndrome

Adv Pediatr. 1994:41:305-42.


1. Fragile X syndrome is defined by the combination of a characteristic phenotype, cognitive impairment, the presence of a fragile site (gap) detectable in folate-free culture medium on Xq27.3 called FRA X A, and transcriptional inhibition, through overmethylation, of an mRNA protein-binding gene called FMR-1. 2. It is inherited in an atypical X-linked dominant way and affects about 1 in 1000 males and 1 in 2000 females; about 1 in 700 females is a carrier. 3. A characteristic but subtle phenotype includes an elongated face and mandible, large ears, macrocephaly with bizygomatic pinching, soft skin, inconsistent mitral valve prolapse, macroorchidism, mildly shortened stature in adulthood, and characteristic behavior that may resemble autism and attention deficit disorders. Intellectual impairment in affected individuals varies from mild to severe, with a majority of affected males within the moderate range of cognitive disability. Twenty percent of males with the mutation are phenotypically and intellectually unaffected. They ae called transmitting males. 4. Female heterozygotes may be indistinguishable from the general population, or they may have subtle physical signs or both physical and intellectual impairment. 5. Sensory motor integration is the therapy of choice for the learning disabilities in children with fragile X syndrome. The benefits of folic acid supplementation are equivocal. 6. A sensitive and understanding support system for the patient and extended family is an inseparable component of appropriate management of fragile X syndrome. 7. Molecularly the mutation is characterized by varying lengths of DNA fragments consisting of the trinucleotide CGG. It is repeated about 6 to 50 times in the normal population and approximately 51 to 200 times in unaffected individuals with a so-called premuation who are at risk for expansion and transmission to offspring. Individuals with over 200 repeats are usually affected and said to have a full mutation. 8. The physician caring for a family with fragile X syndrome should work with an experienced genetics center, counselor, and a laboratory with expertise.

Publication types

  • Review

MeSH terms

  • Adult
  • Base Sequence
  • Child
  • Chromosome Fragile Sites
  • Chromosome Fragility
  • Clinical Protocols
  • Connective Tissue Diseases / genetics
  • DNA / analysis
  • Diagnosis, Differential
  • Female
  • Folic Acid / therapeutic use
  • Fragile X Syndrome* / complications
  • Fragile X Syndrome* / drug therapy
  • Fragile X Syndrome* / genetics
  • Gene Amplification
  • Genetic Linkage
  • Genetic Markers
  • Heterozygote
  • Humans
  • Male
  • Mental Disorders / genetics
  • Molecular Sequence Data
  • Mutation
  • Patient Education as Topic
  • Pedigree
  • Phenotype
  • Repetitive Sequences, Nucleic Acid / genetics
  • X Chromosome


  • Genetic Markers
  • DNA
  • Folic Acid