![]() Autistic disorder ( n = 447) and PDD-NOS ( n = 454) were the predominant diagnoses. We evaluated a combined cohort of 933 patients (755 males and 178 females ) ( Table 1). We present here clinical genetic test results, including those from karyotype, fragile X testing, and CMA, and discuss the implications for clinical care for a large cohort of patients with ASD. 7– 9 Research studies for patients with ASD suggest a similar detection rate of ~10% using CMA, 10– 12 but the diagnostic yield in large clinical cohorts has not been well studied. 6Īrray comparative genomic hybridization (array CGH) also called chromosomal microarray analysis (CMA), detects clinically significant CNVs in at least 10% of patients with a variety of developmental problems such as developmental delay, MR, and multiple congenital anomalies. Subtelomeric fluorescence in situ hybridization (ST-FISH) can detect submicroscopic CNVs in patients with mental retardation (MR), but authors of the largest study of ST-FISH found pathogenic changes in only 2.6% of 11 688 unselected cases of MR, 5 and no changes were found by ST-FISH in 1 small study of patients with ASD. 3, 4 Karyotyping will not detect submicroscopic genomic deletions and duplications or copy-number variants (CNVs) smaller than ~5 megabases (Mb). G-banded karyotyping for chromosomal abnormalities and fragile X testing are currently recommended as first-tier genetic tests, and are abnormal in up to 5% of patients. 3 Most children with ASD do not have dysmorphic features or other medical problems associated with a recognizable genetic syndrome, and genetic testing is crucial to identifying a cause for ASD in this population. Other syndromes are not easily recognized in young children, as in fragile X syndrome, which accounts for ~2% of ASD cases. Autism may be a component of genetic syndromes with distinct clinical features, as in tuberous sclerosis and Rett disorder. Genetic factors increase the risk of developing ASD, 2 but the specific genetic cause for an individual patient can be elusive. The prevalence of autistic disorder is ~, and the prevalence of ASD is ~, affecting many more males than females. ASD occurs in all racial, ethnic, and social groups. These diagnoses are also collectively known as autism spectrum disorders (ASDs). The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) category of pervasive developmental disorders includes autistic disorder, pervasive developmental disorder-not otherwise specified (PDD-NOS), Asperger disorder, childhood disintegrative disorder, and Rett disorder. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients.Īutism is a complex neurobehavioral disorder that includes impairments in social interaction, developmental language and communication deficits, and rigid, repetitive behaviors. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changesin7.3%(51 of 697) and 5.3%(8 of 151) of patients, respectively, both higher than karyotype. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA results for 59 of 848 patients (7.0% ) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. ![]() Karyotype yielded abnormal results in 19 of 852 patients (2.23% ), fragile X testing was abnormal in 4 of 861 (0.46% ), and CMA identified deletions or duplications in 154 of 848 patients (18.2% ). Miller, MD, PhD a, b, c, n, on behalf of the Autism Consortium Clinical Genetics/DNA Diagnostics Collaboration Walsh, MD, PhD, a, c, n Bai-Lin Wu, PhD, MMed, a, b, c, p and David T. Milunsky, MD, a, i, o Leonard Rappaport, MD, a, c, g James F. ![]() Lowe, MS, a, e Alison Schonwald, MD, a, c, g Michael Robbins, MD, a, c, h Fuki Hisama, MD, a, c, n Robert Wolff, MD, a, c, h Ronald Becker, MD, a, c, g Ramzi Nasir, MD, MPH, a, c, g David K. Kowalczyk, MA, MPH, a, i Beth Rosen-Sheidley, MS, a, j Caroline McGowan, MS, a, n Andrew W. Frazier, MD, a, k, l Iris Silverstein, MD, a, m Jonathan Picker, MBChB, PhD, a, c, n Laura Weissman, MD, a, c, g Peter Raffalli, MD, a, c, h Shafali Jeste, MD, a, c, h Laurie A. ![]() Holm, MD, MPH, a, c, e, f Carolyn Bridgemohan, MD, a, c, g Magdi M. ![]()
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