49,XXXXY, a rare genetic disorder: The Relationship with Autism Spectrum Disorders (ASD), Developmental delay, and Testosterone (P3.305)

Objective: To determine incidence of ASD in 49. XXXXY Background: 49,XXXXY, a variant of 47,XXY occurs 1:85,000–100,000 births. Major neurological manifestations include neurocognitive delays and oral dyspraxia. Early testosterone treatment before 12 months of age is advocated for enhancing cognitive abilities, especially speech. Design/Methods: 73 Boys with 49,XXXXY from the US, Italy, UK, Honduras, and Brazil underwent comprehensive multidisciplinary evaluations focused on speech and language, and neurobehavioral testing including the Gilliam Autism Rating Scale – 3 rd Edition (GARS-3). Informed consent and ethics approval was obtained for all subjects. Results: Boys spoke in 2-word combinations at 33 months, with variation between countries. Average age for 2-word combinations was 26.7 months in the USA, 34.9 months in the UK, and 36 months in Italy. Receptive vocabulary skills reached a mean scaled score (SS) of 75. Expressive vocabulary skills reached a mean SS of 64.7. Expressive vocabulary skills varied significantly between those who had received early testosterone treatment (SS=68.27) and those who had not (SS=57.55). Non Verbal IQ were a mean score of 76 (normal 85–100 ). Of the thirty-three assessed for ASD with the GARS-3, 21 (63.6%) were unlikely to have ASD and 12 (36.4%) were rated as very likely . Regarding 49,XXXXY boys who had received testosterone treatment (21), 15 (71.48%) tested unlikely to have ASD while 6 (28.6%) were very likely. Of the 12 children who had not received testosterone replacement, the likelihood for ASD was 50%. Conclusions: This is a large sample size for this rare disorder and suggests increased incidence of autism vulnerability related to the additive X chromosomes. Neurodevelopmental results indicate a potential treatment effect on expressive language skills for those who received testosterone. Results indicate a relationship between the implementation of testosterone treatment and a decrease in the likelihood of ASD. More work is needed to fully elucidate and follow this cohort. Study Supported by: N/A Disclosure: Dr Gropman has nothing to disclose. Dr. Chea has nothing to disclose. Dr. Lasutschinkow has nothing to disclose. Dr. Samango-Sprouse has nothing to disclose.