Approach Considerations

Fragile X DNA testing should be the first test ordered.

If the history or physical findings suggest additional concerns, consider the following:

High-resolution cytogenic studies with fluorescence in situ hybridization (FISH) testing for Prader-Willi, Angelman, and Williams syndromes
Creatine phosphokinase measurement - To rule out muscular dystrophy
Determination of lead level - To rule out lead poisoning
Urine organic acid test
Plasma amino acid test
Lactate and/or pyruvate test - To rule out mitochondrial disorders
Serum ammonia test - To rule out urea cycle defects
Test for very long fatty acids - To rule out peroxisomal disorders
Test of thyroid-stimulating hormone - To rule out hypothyroidism
Gene sequencing for MECP2 (Rett's Syndrome)
Polymerase Chain Reaction (PCR) for Fragile X syndrome

Hearing testing

A hearing test should be administered.^[35]A hearing test should be performed by a pediatric audiologist and should be repeated even if the test results were normal at birth. Testing of children usually requires the presence of 2 pediatric audiologists.

DNA Testing and High-Resolution Cytogenetic Studies with FISH

Fragile-site mental retardation 1 gene (FMR1) deoxyribonucleic acid (DNA) testing for Fragile X syndrome and premutation involvement as indicated.^[21]

Genetic testing should be considered, even if no obvious dysmorphic features are found in the physical examination. Many individuals with Fragile X syndrome appear physically normal (see the image below).

Young child with fragile X syndrome who does not have obvious dysmorphic features. Courtesy of Randi J Hagerman, MD, FAAP.

Gene Sequencing for MECP2 (Rett's Syndrome)

High-resolution cytogenetic studies with FISH are used to test for 15q duplication, which has been found in 3%–5% of individuals with autism.^[7]

Comparative Genomic Hybridization

Comparative genomic hybridization (CGH) is now often recommended to identify a greater number of subtle cytogenetic abnormalities in pervasive developmental disorder (PDD). Up to 20% of individuals with a ASD may have these slight abnormalities.^[6]

Imaging Studies

Brain magnetic resonance imaging (MRI), but not head computed tomography (CT) scanning, may be helpful in the clinical assessment of global developmental delay, as the Practice Committee of the Child Neurology Society outlined in 2003.^{[36, 37]}

Functional MRI, magnetic resonance spectroscopy (MRS), positron emission-tomography (PET) scanning, and single photon CT (SPECT) scanning remain research tools. MRS is growing in promise as a tool in screening for conditions such as a deficiency in the creatine transporter gene.^[38]

Also see PET Scanning in Autism Spectrum Disorders.

Electroencephalography

Results are abnormal in 25% of children with ASD.

Results are abnormal in all children with Rett syndrome.

Results can be diagnostic for children with Landau-Kleffner syndrome (LKS), because seizure activity in the brain speech centers often causes this rare disorder.

Psychological and Neuropsychological Testing

In older children, testing may help distinguish atypical ASD or pervasive developmental disorder (PDD) not otherwise specified from a mood disorder, early presentation of schizophrenia, or schizotypal personality disorder.^[39]

Testing may reveal verbal and nonverbal learning disabilities.

Treatment & Management

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Media Gallery

Young child with fragile X syndrome who does not have obvious dysmorphic features. Courtesy of Randi J Hagerman, MD, FAAP.

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Author

Sufen Chiu, MD, PhD Associate Clinical Professor (Volunteer Faculty), University of California, Davis, School of Medicine; Staff Physician, Mercy Medical Group

Sufen Chiu, MD, PhD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, American Psychiatric Association, California Medical Association, Sierra Sacramento Valley Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Randi J Hagerman, MD, FAAP Professor of Pediatrics, Medical Director of the MIND Institute, Endowed Chair in Fragile X Research, Division of Developmental/Behavioral Pediatrics, University of California Davis Medical Center

Randi J Hagerman, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics, Society for Pediatric Research, Society for Developmental and Behavioral Pediatrics, Western Society for Pediatric Research

Disclosure: Received grant/research funds from Roche for pi on study; Received grant/research funds from Novartis for pi on study; Received grant/research funds from Seaside therapeutics for pi on study; Received grant/research funds from Johnson and Johnson for pi on study; Received grant/research funds from Forest for pi on study; Received grant/research funds from curemark for pi on study.

Sandra M DeJong, MD, MSc Assistant Professor of Psychiatry, Harvard Medical School; Active Staff, Department of Psychiatry, Cambridge Health Alliance

Sandra M DeJong, MD, MSc is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Association of Directors of Psychiatric Residency Training, American Psychiatric Association, Association of Women Psychiatrists, Massachusetts Psychiatric Society, New England Council of Child and Adolescent Psychiatry

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Caroly Pataki, MD Health Sciences Clinical Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, David Geffen School of Medicine

Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, Physicians for Social Responsibility

Disclosure: Nothing to disclose.