Case Report: A Disease Phenotype of Rett Syndrome and Neurofibromatosis Resulting from A Bilocus Variant Combination

Autism spectrum disorder (ASD) is an increasingly prevalent early onset neurodevelopmental disorder with social communication and interaction impairment and restrictive repetitive behavior (Kliegman, 2020). ASD is unique in terms of severity and also due to the presence of neurodevelopmental, behavioral and medical co-morbidities. The genetic influences of ASD are mainly deletions or duplications in genes primarily involved in early brain development, thereby mainly disrupting neural connectivity. In addition, ASD is associated with genetic syndromes like Fragile X syndrome, Rett syndrome, Down syndrome, Smith-Lemli-Opitz syndrome and Angelman syndrome (Kliegman, 2020). The recommended initial workup of an individual with ASD includes chromosomal microarray, FMR1 gene repeat or methylation analysis for boys and MECP2 gene sequencing for girls, with PTEN gene mutation analysis done if the head circumference is more than 2.5 SD above the mean. In cases where the above studies are negative and the child has other features such as developmental delay and autism, whole exome sequencing is being increasingly utilized as the cost of such testing declines. …