In an assessment at 18 years, she was noted to need substantial help with self-care activities and could not understand or follow instructions. Her interactions and behaviors were immature, characterized as a 4-year-old level by her school evaluations. She had short stature and obesity (weight 88.2 kg, > 98th centile; height 153.0 cm, 6th centile; BMI 37.7 kg/m2, 98th centile) with macrocephaly (head circumference 58 cm; > 98th centile) (Table 1). She had a history of continuously gorging or binge eating to the point of vomiting, requiring her parents to restrict her food intake.
She was mildly dysmorphic, with sparse lateral eyebrows, telecanthus, left preauricular pit, prominent cupid bow configuration of the upper lip, and slack facial expression. She had numerous self-inflicted, skin-picking lesions on her arms, in various stages of healing, and one hyperplastic keloidal scar elsewhere. Her speech was fluent but very simple, with sound substitution errors very typical of a young child. There was periodic echolalia, in addition to outbursts of out-of-context speech, without regard to interrupting other speakers. Negative genetic testing included Prader-Willi/Angelman syndrome methylation and MLPA, fragile X, and CNV analysis via SNP microarray. However, areas of homozygosity were identified across multiple chromosomes, with an overall percentage of autosomal/genomic homozygosity of 2.5%. No candidate recessive genes were identified within the homozygous regions. As no specific disease could be suspected on the basis of the clinical presentation, family trio sequencing of GeneDx's Autism/ID Xpanded Panel with 2308 genes was performed, using oral rinse samples from her and both parents. This patient was identified through GeneMatcher.
All data generated or analyzed during this study are included in this article. The primer sequences for Sanger sequencing, Real-time PCR, and RT-PCR will be provided upon request.
All study participants have given written informed consent, and the genetic study has been approved by the Augusta University Institutional Review Board.
All participating families agreed to publish the clinical description and photos.