eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Fragile X Syndrome: Differential Diagnoses & Workup

Author: Jennifer A Jewell, MD, MS, Clinical Assistant Professor, Department of Pediatrics, University of Vermont School of Medicine; Pediatric Hospitalist, The Barbara Bush Children's Hospital at Maine Medical Center
Contributor Information and Disclosures

Updated: Mar 2, 2009

Differential Diagnoses

Attention Deficit Hyperactivity Disorder
Ehlers-Danlos Syndrome
Marfan Syndrome
Pervasive Developmental Disorder
Pervasive Developmental Disorder: Autism
Pervasive Developmental Disorder: Rett Syndrome

Other Problems to Be Considered

Learning disabilities
Lujan syndrome

Workup

Imaging Studies

  • Radiography of the spine is recommended in patients with fragile X syndrome to evaluate for scoliosis.
  • Echocardiography is recommended to exclude mitral valve prolapse.

Other Tests

  • Cytogenetics
    • Cytogenetic testing for fragile X syndrome is not as sensitive as molecular testing, with a false-negative result rate of approximately 20%. Thus, DNA testing for fragile X syndrome is recommended.
    • Karyotyping may reveal other chromosomal anomalies, and both a standard karyotype and DNA testing are suggested when a possible diagnosis of fragile X syndrome is considered.
  • Molecular genetics: The criterion standard diagnostic test involves molecular genetic techniques. The exact number of CGG triplet repeats can be determined. Southern blot and polymerase chain reaction (PCR) are the 2 methods of genetic analysis that are currently available.
    • Southern blot analysis provides a more accurate estimation of the number of CGG triplet repeats if a full mutation is present (with a large CGG expansion). It can also be used to evaluate the degree of methylation at the CGG repeat site.
    • PCR is faster, requires a minimal sample, and is less expensive than Southern blot analysis. Additionally, PCR more accurately estimates the number of CGG triplet repeats if a premutation is present (with small-to-moderate increases in CGG repeats). Recent success with fluorescent methylation-specific PCR and GeneScan analysis may further expand diagnostic options.
  • A comprehensive developmental evaluation by a speech and language therapist, physical therapist, and occupational therapist is recommended to assess weaknesses and to identify areas in which improvement is needed most. As the patient matures, repeat evaluation may be necessary.
  • Ophthalmology examinations are required.
  • Routine auditory examinations are advised; otolaryngology referral for chronic otitis media and evaluation for pressure equalization (PE) tube placement are recommended.

More on Fragile X Syndrome

Overview: Fragile X Syndrome
Differential Diagnoses & Workup: Fragile X Syndrome
Treatment & Medication: Fragile X Syndrome
Follow-up: Fragile X Syndrome
References
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Further Reading

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Keywords

fragile X syndrome, marker X syndrome, Martin-Bell syndrome, retardation, mental retardation, mental deficiency, folate-deficient thymidine-deficient medium, FRAXA, X-linked mental retardation, fragile X-associated tremor/ataxia syndrome, FXTAS, cerebellar ataxia, autonomic dysfunction, severe tremor, neurodegeneration, memory loss, anxiety, irritability, autistic-like behavior, autisticlike behavior, cognitive disorders, neurobehavioral disorders, premature ovarian failure, attention deficits, depressed affect, aggressive tendencies, abstract thinking deficiency, developmental delays, echolalia, pes planus, pectus excavatum, joint laxity, scoliosis, joint dislocation, recurrent sinusitis, otitis media, decreased visual acuity, apnea, macroorchidism

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Contributor Information and Disclosures

Author

Jennifer A Jewell, MD, MS, Clinical Assistant Professor, Department of Pediatrics, University of Vermont School of Medicine; Pediatric Hospitalist, The Barbara Bush Children's Hospital at Maine Medical Center
Jennifer A Jewell, MD, MS is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, Massachusetts Medical Society, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Michael Fasullo, PhD, Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College
Michael Fasullo, PhD is a member of the following medical societies: Radiation Research Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David Flannery, MD, FAAP, FACMG, Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia
David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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