Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) affect more than 4.6 million Americans and there is a growing body of evidence that shows strong support for the role of genetics in NDDs. To better serve the needs of clinicians and patients, we offer a range of diagnostic testing options for NDDs.

NDDs are disabilities associated primarily with the functioning of the brain and neurological system. Individuals often present with global developmental delays (GDD), intellectual disabilities (ID) and/or characteristics of autism spectrum disorders (ASD). Epilepsy can also be common. 

Intellectual Disability
2-3% of Americans are diagnosed with intellectual disability (ID).1 ID is defined as:2

  • Intelligence quotient (IQ) approximately 70 or below
  • Onset before 18 years of age 
  • Impairments in adaptive functioning in at least 2 of the following areas: communication, social/interpersonal skills, use of community resources, self-direction, functional academic skills, work, leisure, health, and safety

ID is a developmental consequence that can be syndromic (occurring with other congenital anomalies or medical problems) or non-syndromic (isolated). Causes include complex inherited conditions resulting from chromosome or single gene changes/errors during embryogenesis, prenatal and perinatal complications, and inborn errors of metabolism. ID can result from mutations in genes that are inherited in a variety of patterns, including autosomal dominant, autosomal recessive, and X-linked.

Genetic testing can identify the underlying cause for approximately 1 in every 5 affected individuals,3 and is recommended for all children with ID by the American College of Medical Genetics and Genomics (ACMG), the American Academy of Neurology (AAN) and the American Academy of Pediatrics (AAP). 3,4,5 The following testing strategy incorporates these guidelines and could be considered in the absence of other indications:

Autism Spectrum Disorders
1-2% of American children are found to have an autism spectrum disorder (ASD).6 ASDs are a group of NDDs that can cause significant behavioral, social and communication difficulties that begin in early childhood ASDs encompass autism, Asperger syndrome, and pervasive developmental delay-not otherwise specified (PDD-NOS).

In some individuals, the ASD is caused by an inherited condition, such as fragile X syndrome, Rett syndrome, or tuberous sclerosis complex. Confirmation of a genetic cause helps guide medical management and recommendations for an individual/family, as well as tailor genetic counseling and recurrence risk estimates. 

Genetic testing can confirm the underlying cause for 30-40% of affected individuals, 7 and is recommended by the American College of Medical Genetics and Genomics (ACMG), the American Academy of Neurology (AAN) and the American Academy of Pediatrics (AAP). 3,4,5 The following testing strategy incorporates these guidelines and could be considered in the absence of other indications.

Our Neurodevelopmental Testing Includes:

Test Name Turnaround Time
SNP Array 2-3 weeks
Fragile X-associated disorders 1-2 weeks
IDNext
(140 gene panel for syndromic and non-syndromic ID)
5-7 weeks
AutismFirst
(16 genes, ACMG-recognized syndromes)
3-5 weeks
AutismNext
(48 genes, syndromic and non-syndromic autism)
4-6 weeks
Rett/AngelmanNext
(22 genes for Rett, Angelman and related disorders)
3-5 weeks
Neurodevelopment-Expanded
(196 gene panel for ID, ASD and epilepsy)
8-10 weeks
Rett syndrome
(MECP2 gene sequencing and deletion/duplication)
2-4 weeks
Angelman syndrome
(methylation studies with reflex to UBE3A gene sequencing
and deletion/duplication)
2-4 weeks
PTEN-related disorders 1-3 weeks
Tuberous sclerosis complex 2-4 weeks
CdLSNext
(5 gene panel for Cornelia de Lange syndrome)
2-4 weeks
Rubinstein-Taybi syndrome 2-4 weeks
Coffin-Lowry syndrome 2-4 weeks
Smith-Magenis syndrome 2-4 weeks
Sotos syndrome 2-4 weeks
ExomeNext 8-12 weeks
(rapid option is 2-5 weeks)

 

References

  1. Larson SL, et al. Prevalence of mental retardation and/or developmental disabilities: Analysis of the 1994/1995 NHIS-D. MR/DD Data Brief. Minneapolis, MN: Institute on Community Integration, University of Minnesota. 2000.
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC. 2013.
  3. Miller DT, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010 May 14;86(5):749-764.
  4. Michelson DJ, et al. Evidence report: Genetics and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2011 Oct 25;77(17):1629-1635.
  5. Moeschler JB, et al. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics. 2014 Sep;134(3):903-918.
  6. Centers for Disease Control and Prevention. Prevalence of autism spectrum disorder-Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. Mar 30 2012. 61(3):1-22.
  7. Schaefer GB, et al. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013 May;15(5):399-407.