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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brachmann-de Lange syndrome (BDLS) is a rare multiple congenital anomaly/mental retardation (MCA/MR) syndrome with variable expression, making diagnosis of mild cases difficult. The most consistent manifestations appear to be the characteristic face, which can be subtle in children who are mildly affected [Ireland and Burn, 1991: Twelfth Annual David W. Smith Workshop on Malformations and Morphogenesis]. Other aspects of the syndrome include variable degrees of mental retardation, growth retardation, structural abnormalities of the limbs, and behavior abnormalities, noted to be "autistic" [Jones, 1988: "Smith's recognizable patterns of human malformation"]. Johnson et al. [1976: Pediatr Res 10:843-850] described a behavior phenotype felt to be common in patients with BDLS. They predicted that patients with BDLS may respond to "behavioral intervention". Other behavior abnormalities in BDLS have been reported [Barr et al., 1971: Neuropadiatrie 3:46-66; Hawley et al., 1985: Am J Med Genet 20:453-459]. We report on a 6-year-old boy with the facial characteristics of BDLS, normal birth weight, prenatal onset of a small head relative to length, postnatal onset growth deficiency, nearly normal psychomotor development with onset of clear developmental delays by 2 years. He developed behavior problems similar to those seen in other patients with BDLS. These behaviors are most consistent with Pervasive Development Disorder-NOS (PDD), and Autistic Disorder [DSM-III-R, 1987] which encompasses a spectrum of mild to severe autistic behaviors. We report successful in-patient care utilizing medical and behavioral techniques to reduce the frequency of the behaviors. We feel that the presence of the characteristic behaviors may be helpful in confirming the diagnosis of BDLS.
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PMID:Mild Brachmann-de Lange syndrome. Delineation of the clinical phenotype, and characteristic behaviors in a six-year-old boy. 750 94

Array CGH (comparative genomic hybridization) screening of large patient cohorts with mental retardation and/or multiple congenital anomalies (MR/MCA) has led to the identification of a number of new microdeletion and microduplication syndromes. Recently, a recurrent copy number variant (CNV) at chromosome 16p11.2 was reported to occur in up to 1% of autistic patients in three large autism studies. In the screening of 4284 patients with MR/MCA with various array platforms, we detected 22 individuals (14 index patients and 8 family members) with deletions in 16p11.2, which are genomically identical to those identified in the autism studies. Though some patients shared a facial resemblance and a tendency to overweight, there was no evidence for a recognizable phenotype. Autism was not the presenting feature in our series. The assembled evidence indicates that recurrent 16p11.2 deletions are associated with variable clinical outcome, most likely arising from haploinsufficiency of one or more genes. The phenotypical spectrum ranges from MR and/or MCA, autism, learning and speech problems, to a normal phenotype.
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PMID:Extending the phenotype of recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism and in normal individuals. 2902 26

Using aCGH, we have identified a pericentromeric deletion, spanning about 8.2 Mb, within 16p11.2-p12.2 in a patient with developmental delay (DD) and dysmorphic features. This deletion arose de novo and is flanked by segmental duplications. The proposita was the only child of healthy nonconsanguineous parents, born after an uneventful pregnancy, at 40 weeks gestation, by normal delivery. She was referred to us at age 3 10/12 years for evaluation of DD and absent speech. On examination, there were a flat face; low-set, posteriorly rotated ears; high-arched palate; hypotonic face; right single palmar crease; long, thin fingers; and a sacral dimple. Her height was at the 50th centile, weight at the 25th, and OFC at the 30th. Results of DNA FraX, HRB chromosomes, metabolic work-up, audiologic evaluation, brain MRI, electroencephalogram, and heart/abdomen ultrasonography were normal. When last seen, aged 8 years, she had a moderate intellectual disability (ID) and poor speech. She was hyperactive with short attention span and difficulty in concentration, but, based on formal testing, did not have autism. Our patient shows common clinical features to the four individuals described by Ballif et al. [Ballif et al. (2007); Nat Genet 39:1071-1073], and further characterizes the new microdeletion syndrome of 16p11.2-p12.2. aCGH suggests that the deletions of all cases share the same distal breakpoint. Of note, the proximal breakpoint of our proposita overlaps the distal breakpoint of the autistic patients studied by Kumar et al. [Kumar et al. (2008); Hum Mol Genet 17:628-638] and Weiss et al. [Weiss et al. (2008); N Eng J Med 358:667-675], confirming that the 16p region carrying susceptibility to autism is more centromeric. Our observation further defines two different, contiguous 16p genomic regions, responsible for a distinct MCA/ID syndrome, and for autism, respectively.
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PMID:Further characterization of the new microdeletion syndrome of 16p11.2-p12.2. 1944 18

Microarray-based cytogenetics is revealing the tremendous fluidity and complexity of the human genome, and is starting to illustrate the implications of genomic variability with respect to human health and disease. In the last few years, the robustness of array-based technologies has provided accurate diagnosis and appropriate clinical management in a timely and efficient manner for identifying genomic defects of congenital and developmental abnormalities including developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASD) and/or multiple congenital anomalies (MCA). The implementation of this technology in these categories of disorders has been thoroughly evaluated and is now recommended as a first-line diagnostic approach for clinically suspected genetic disorders. However, clinical application of array-CGH in postnatal evaluation raises the debate of whether array-CGH will replace traditional cytogenetics in the near future and whether there is still a role for karyotyping and FISH. In this article, we therefore review the current status of array-based technology use for postnatal diagnosis and predict that it will replace standard cytogenetics as a first-line test for clinical evaluation in these population groups.
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PMID:Evolving applications of microarray technology in postnatal diagnosis (review). 2258 Mar 83

Copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) significantly contribute to the etiology of neurodevelopmental disorders, such as developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD). This study summarizes the results of 3.5 years of CMA testing by a CLIA-certified clinical testing laboratory 5487 patients with neurodevelopmental conditions were clinically evaluated for rare copy number variants using a 2.8-million probe custom CMA optimized for the detection of CNVs associated with neurodevelopmental disorders. We report an overall detection rate of 29.4% in our neurodevelopmental cohort, which rises to nearly 33% when cases with DD/ID and/or MCA only are considered. The detection rate for the ASD cohort is also significant, at 25%. Additionally, we find that detection rate and pathogenic yield of CMA vary significantly depending on the primary indications for testing, the age of the individuals tested, and the specialty of the ordering doctor. We also report a significant difference between the detection rate on the ultrahigh resolution optimized array in comparison to the array from which it originated. This increase in detection can significantly contribute to the efficient and effective medical management of neurodevelopmental conditions in the clinic.
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PMID:Clinical Performance of an Ultrahigh Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders. 2797 50

We identified a novel mutation in ASH1L in a patient with severe intellectual disability, growth failure, microcephaly, facial dysmorphism, myelination delay, and skeletal abnormalities. ASH1L is a histone methyltransferase that associates with the transcribed region of all active genes examined, including Hox genes. It catalyzes H3K36 methylation and plays important roles in development. There has been increasing evidence that heterozygous mutation of ASH1L is associated with ID and autism spectrum disorders. We suggest that ASH1L abnormalities may cause a novel MCA/ID syndrome.
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PMID:Novel MCA/ID syndrome with ASH1L mutation. 2839 64