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Fragile X Syndrome
BY: NEHA SINGH, MADDALENA DAL POZZO AND HANA TAKAHASHI.
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Pathology


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Causes
•Trinucleotide (CGG) repeat expansion-:
1.45-54: intermediate expansion repeat number.
2.55-200: carrier/premutation individual repeat number.
3.200-4000: affected individual repeat number.
•Inheritance-:
qAutosomal recessive
qMutations occur/worsen during oogenesis.
qAnticipation-: genetic mutation continue through pedigreeà ↑ length of expansionà ↑ severity of
disease.

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Signs and Symptoms
•Females are likely to show mild symptoms as compared to males.
•Common features are as follows-:
qPhysical phenotype-: long face, prominent forehead, large ears, flat feet, low muscle tone,
macro-orchidism after puberty, hyperextensible thumbs and finger joints and soft skin.
qSpeech-: begin to talk later than other children.
qVision-: strabismus, if left untreated can lead to amblyopia.
qNeurological-: intellectual disabilities, social anxiety, hypersensitivity and repetitive
behavior, ADHD, fluctuating mood, self-harm, aggression and irritability.

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Complications
•Behavioural features-: Autism, ADHD, anxiety disorders.
•Seizures
•Fragile X tremor/ataxia-: observed in carrier/premutation individuals.
qTremor/ataxia- parkinsonism.
qShort term memory loss, executive dysfunction (common).
qIn females ovarian insufficiency; early menopause.
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Diagnosis
1.Count CGG repeats on  X-chromosome with the help of
•Polymerase chain reaction (PCR).
•Methylation status with the help of southern blot analysis.
•2. Prenatal testing:
•Chorionic villus sampling.
•Amniocentesis.
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Treatment
•Medication-: symptoms directed management.
qBehavioural features- ADHD Presentation-: > 5yr old- stimulant preparation e.g. methyphenidate.
qAnxiety/mood disorders- SSRI- SELECTIVE SEROTONIN REUPTAKE INHIBITORS.
qSeizures- anticonvulsants.
•Psychotherapy
•Others-:
qSpecial education.
qVocational training.
qAntidepressants and antipsychotics.
qEarly intervention.

References-:
•Garber, KB; Visootsak J, Warren ST. (2008). “Fragile X syndrome”.
European Journal of Human Genetics. 16 (6): 666–72. doi:10.1038/ejhg.2008.61. PMID 18398441.
•Hagerman RJ; Berry-Kravis E; Kaufmann WE; Ono, M. Y.; Tartaglia, N.; Lachiewicz, A.; Kronk, R.;
Delahunty,
 C.; Hessl, D.; Visootsak, J.; Picker, J.; et al. (2009). “Advances in the treatment of fragile X
syndrome.”
Pediatrics. 123 (1): 378–90. doi:10.1542/peds.2008-0317. PMC 2888470 Freely accessible. PMID
19117905.
•U.S National Library of Medicine (2017).
Retrieved from: https://ghr.nlm.nih.gov/condition/fragile-x-syndrome
•US Department of Health and Human Services | National Institutes of Health (2017).
Retrieved from:
https://www.nichd.nih.gov/health/topics/fragilex/conditioninfo/Pages/commonsymptoms.aspx