P479: PIK3CA-related overgrowth syndrome: To exome or not?

types, including duplications have been reported in SOX 3, 8 and 9.The most frequent are missense variants in the HMG domain which mediates DNAbinding, nuclear trafficking and protein-protein interaction.The SOX6 HMG domain (exons 14-15) are duplicated in our patient.Case Presentation: The proband is a 2-year-old boy with macrocephaly, global developmental delays, autism and developmental regression.He had bilateral inguinal hernia.Macrocephaly was recognized at 9 months of age (Z score= 3.2).He was on target for early developmental milestones: walked and said his first words at 11 months and had a vocabulary of 20 words at 15 months of age.An evaluation for staring spells at 20 months included a video EEG that showed no association with epileptic changes.He had regression of language skills at 23 months and was diagnosed with autism spectrum disorder.He is treated with multiple medications for insomnia.He was delivered at term by C-section for failure to progress after a pregnancy complicated by maternal pregnancy-induced hypertension and preeclampsia.BW was 7lb 1 oz.There were no postnatal complications.Family history was pertinent for ADHD in mother and for father being overweight.Neither had macrocephaly.Macrosomia was noted in patient at age 27 mos (Z score weight= 3.13; for height= 1.51, Z score for HC= 4).At age 4, he continues to have macrocephaly and macrosomia (Z score HC= 5.6, weight= 5.19, height= 2.17).Diagnostic Workup: A head ultrasound (9 mos) was reported to be normal.Brain MRI (age 20 mos) showed nonspecific scattered periventricular and subcortical white matter T2 hyperintensities, but was otherwise normal.Chromosome microarray analysis detected a 5.42 Mb interstitial duplication at 11p15.3p15.1:arr[hg19] 11p15.3p15.1 (10,887,306,448)x3 dn.The duplicated interval of uncertain significance does not include the 11p15 imprinted region associated with BWS and disrupts the SOX 6 gene.Gene-targeted testing showed two intragenic duplications of exons 4-9 and 13-16.SOX6 NM_033326.3