Fraternal Twins With Autism, Severe Cognitive Deficit, and Epilepsy: Diagnostic Role of Chromosomal Microarray Analysis
Section snippets
Case 1
The propositus was a full-term male child of an uneventful twin gestation pregnancy. Parents were healthy, nonconsanguineous white individuals, with no family history of developmental delay or cognitive deficits, seizures, autism, or mental health problems. He had a history of ventricular septal defect. Psychomotor development was severely delayed for motor skills (he sat up at 1 year and walked at 2 years) and for language. He also developed clinical features compatible with the diagnosis of
Case 2
The fraternal twin sister of the propositus was also born at full term with no medical issues. However at 6 months of age, she showed an inability to play and interact with others. She was later diagnosed with severe developmental delay and language impairment. Her clinical progress was very slow. At 7 years, she had some vocalizations, and her language was limited to 2-5 words. She had strabismus, hypotonia, and ataxia. Other symptoms included hyperventilation, stereotypies, constipation, and
Genetic Studies
Chromosomal microarray analysis was performed in our patients to identify copy number variations associated with an underlying genetic etiology.
The studies were approved by the institutional review board of St. Christopher’s Hospital. The patients had normal results for an extensive range of tests, including a detailed metabolic investigation and routine karyotyping. Genomic DNA was isolated from blood for whole-genome array single nucleotide polymorphism comparative genomic hybridization.
Discussion
Chromosomal microarray has emerged as a powerful tool to identify genomic abnormalities associated with a wide range of developmental disabilities. The frequency of disease-causing copy number variants has been described in 20%-25% of children with moderate to severe intellectual disability accompanied by malformations or dysmorphic features and in 5%-10% of cases of autism.3 It is therefore increasingly used as a first-line test in the diagnostic workup or children with autism, especially if
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