S is a 12-year-old boy with autism spectrum disorder (ASD), seizure disorder, cerebral palsy, and intellectual disability who presented to the primary care clinician for a preventative care visit.
S was born at full term after an unremarkable pregnancy. His developmental delays were first noted at around 8 months, when he could not sit independently and had intermittently poor eye contact. He was referred to Part C Early Intervention and subsequently evaluated by a neurodevelopmental pediatrician, where he was noted to be hypotonic, with delayed motor and cognitive skills. Initial genetics evaluation included karyotype, fragile X testing, Angelman and Prader-Willi DNA fluorescence in situ hybridization probes, POLG sequencing, MECP2 testing, a microarray, creatinine kinase, very long-chain fatty acids, lymphocyte arylsulfatase, urine organic acids, and plasma amino acids, all of which were normal.
As time progressed, S continued to have motor and communication delays and developed choreic movements. He also developed episodes concerning for seizure, including periods of staring while awake and episodes of extremity shaking lasting a few seconds with associated eye deviation, which eventually progressed to generalized seizures. He also developed periods of lethargy. Outpatient workup included several EEGs, which were notable for foci in the right frontal and left temporal regions. He has had several brain MRIs showing generalized volume loss and had critical laboratory tests during a period of lethargy, which were unconcerning. He was treated with multiple antiseizure medications. He was diagnosed with ASD at age 5 years because of delayed language, poor social communication, and repetitive behaviors.
Over time, S continued to experience global developmental delays and autistic-like behaviors and remained minimally verbal. However, clinicians noted a number of developmental strengths, including a generally positive mood, a willingness to participate in therapy, improved receptive language skills, attachment to his mother, and a love of nature and the outdoors. He participated in a number of therapy modalities including speech/language therapy, occupational therapy, physical therapy, applied behavioral analysis, aqua therapy, partner-assisted scanning, and therapeutic horseback riding.
In 2019, whole-exome sequencing was newly covered by the state Medicaid program, and testing was obtained in 2020. Whole-exome sequencing revealed a de novo STXBP1 pathogenic variant c.874C>T (p.Arg292Cys), which is associated with developmental and epileptic encephalopathy. His presentation is consistent with STXBP1 encephalopathy including refractory epilepsy, ASD, intellectual disability, and movement disorders.
What are important considerations in genetic testing for children with autism? How does a genetic testing result alter management for clinicians and families?