Neurodevelopmental disorders (NDDs) affect more than 4.6 million Americans1 and include both intellectual disabilities (ID) and autism spectrum disorders (ASD). There is a growing body of evidence that shows strong support for the role of genetics in NDDs. To better serve the growing needs of clinicians and patients, Ambry offers a range of diagnostic testing options for these indications.
NDDs are disabilities associated primarily with the functioning of the brain and neurological system. Individuals often present with intellectual disabilities (ID) and/or characteristics of autism spectrum disorders (ASD). The overlapping and non-specific nature of these symptoms can bring diagnostic challenges, as these clinical signs can exist in combination with other medical concerns or on their own. Making this distinction is a critical step in arriving at an accurate diagnosis.
Genetic Testing Strategy for the Child With Unexplained ID +/- Characteristics of ASD
In the absence of other indications, this testing strategy could be considered. It incorporates recommendations from the American College of Medical Genetics and Genomics (ACMG), the Amercican Academy of Neurology (AAN), and the American Academy of Pediatrics(AAP).2,3,4,5 Clinical evaluation(s) may suggest that single gene testing or karyotyping are more appropriate initial steps.
A tiered approach offers the option of fragile X DNA analysis with chromosomal microarray, with a reflex to several tests most appropriate to the patient phenotype. ExomeNext is available as a reflex test if initial testing is inconclusive.
Intellectual Disability (ID)
ID is a developmental consequence of both syndromic and non-syndromic origins. Causes include complex inherited conditions resulting from chromosome or single gene changes, errors during embryogenesis, prenatal and perinatal complications, and inborn errors of metabolism.
DSM-56 defines ID as:
X-linked intellectual disability (XLID) affects approximately 1/600-1/1,000 males and a significant number of females.3 XLID is associated with more than 200 inherited conditions linked to >90 genes on the X chromosome.7 Ambry’s XLID genetic test uses next generation sequencing to simultaneously analyze 81 genes linked to X-linked intellectual disability. Research suggests that approximately 42% of patients with XLID will present with a mutation in one of these genes.8
Autism Spectrum Disorders (ASD)
Children with signs of an ASD may have co-occurring inherited conditions, such as fragile X syndrome, Rett syndrome, and PTEN-related disorders. Ambry offers testing for these conditions to help clinicians accurately determine the underlying genetic cause of a child’s symptoms. Confirmation of a genetic cause helps tailor medical management and recommendations for an individual/family.
|Fragile X syndrome||FMR1||7-14 days|
|Rett/Atypical Rett syndrome||MECP2, CDKL5, FOXP2, MEF2C||7-42 days|
|XLID panel||81 genes for X-linked intellectual disability||84-112 days|
|PTEN-related macrocephaly and autism spectrum disorder||PTEN||7-21 days|
|Autism spectrum disorder||FMR1, PTEN, MECP2, CDKL5, FOXP2, MEF2C, chromosomal microarrays (SNP+CGH and 180K oligo options)||7-42 days|
|Intellectual disability||FMR1, XLID panel, chromosomal microarrays (SNP+CGH and 180K oligo options)||7-112 days|
|Chromosomal microarray||SNP+CGH and 180K oligo options||10-21 days|
|ExomeNext||ExomeNext and ExomeNext-Rapid||14-84 days|