Tests offered for neonatologists and pediatricians

• Fluorescene In Situ Hybridization (FISH) - Microdeletions
   Angelman syndrome       Soto syndrome
   Cri du Chat-Syndrome      SRY
   DiGeorge/VCFS/CATCH22    Steroid Sulfatase(STS)
   Kallmann syndrome       Wolf-Hirschhorn syndrome
   Miller-Dieker syndrome     Williams Beuren syndrome
   Prader-Willi syndrome      XIST
   Smith-Magenis syndrome
• Cyto SNP-850K Microarray for Constitutional Abnormalities - Blood
• Fragile X Syndrome
• Microarrays and Next Generation Sequencing for Autism

 What is Autism Spectrum Disorder?

Autism spectrum disorder (ASD) is a developmental disorder usually appearing in children under the age of three. This disorder causes social, communication (verbal and nonverbal), and behavioral problems with the severity ranging between individuals.

 What causes ASD?

In many cases the cause is unknown, and no single-etiology had been identified. However, there are some known genetic factors that seem to play an important role in the cause. ASD is thought to be influenced by genetic and environmental factors.

 How is ASD Currently Diagnosed?

• Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
• Autism diagnostic Observation Schedule– 2nd edition (ADOS-2)
• Autism Diagnostic Interview– Revised (ADI-R)
• Family history studies
• Chromosomal analysis
• Fragile X testing is routinely offered for children with ASD because it is the most common known single gene cause of ASD
• Chromosomal Microarray (CMA) is offered in the absence of a specific diagnosis. It provides a genome wide characterization of gene transcription, single nucleotide variation, copy number variation and epigenetic cytosine methylation.
• Next Generation Sequencing Panel for Autism is offered after microarray for more specific diagnosis if needed.

 Why is genetic testing is a vital component to the diagnostic evaluation of children with ASD?

• Definitive etiologies can lead to more specific resources
• May lead to changes in medical management
• The diagnosis may have implications for other family members
• Give more information about what to expect in your child’s medical and developmental future
• Associated medical conditions can be managed proactively
• May lead to opportunities to participate in clinical trials for new treatments
• Families are spared long, emotionally and financially exhausting diagnostic journeys
• Reveal the likelihood that future children could have the same genetic condition

 Clinical Background

GDI’s Autism Sequencing Panel uses expert-defined content and proven next-generation sequencing technology to efficiently and cost-effectively assist in the evaluation of characteristics associated with Autism Spectrum Disorders.

Included in GDI’s Autism Sequencing Panel are genes reported in the Online Mendelian Inheritance in Man (OMIM) database on autism; genes with recurrent mutations suspected in development delays; genes with reported mutations as found in case studies involving developmental delay characteristics; genes from other publicly available ASD panels; and genes from summaries of ASD-relevant genes.

Autism Susceptibility Genes: SHANK2, ZNF804A, SLC9A9, ST7, GRPR, RPL10

Intellectual Disability Genes : DHCR7, KIRREL3, MBD5, SATB2, MEF2C, ATRX, KDM5C, OPHN1, PCDH19, PHF6, PQBP1, RAB39B, ARX, CDKL5, PTCHD1

Developmental Issue Genes: SOX5, CHD8, ANKRD11, CREBBP, PAFAH1B1, FOXP1, FOXP2, NSD1, AUTS2, HOXA1, VPS13B, EHMT1, CASK, FGD1, L1CAM, NHS, RAI1

Cellular Control Process Genes: SPAST, TSC1, TSC2, NIPBL, PON3, GABRG1, KLHL3, PDE10A, DLGAP2, GNA14, DPP6, CACNA1C, KCTD13, C18orf1, KATNAL2, SLC9A6, SMC1A, PNKP, UBE3A, MID1, ZNF507, SHANK3, AP1S2, AVPR1A, FOLR1, GABRB3, GRIN2B, IMMP2L, CNTNAP2, CNTNAP5, LAMC3, MECP2, NLGN3, NRXN1, PCDH9, PTEN, BDNF, RELN, SCN1A, SCN2A, SLC6A4, SMG6, STK3

Transcriptional Process Genes: FOXG1, TCF4, SNRPN, FMR1, NEGR1, NTNG1, ZNHIT6, PIP5K1B

Other genes included: BRAF, DOCK4, MET, PTPN11, CHD7, DMD, DPP10, HPRT1, MED12, RBFOX1, ZEB2