EP136: An exploration of the impact of Hormonal Replacement Therapy (HRT) upon vocabulary skills in males with 49,XXXXY

Abstract

49,XXXXY is a rare variant of 47,XXY, Klinefelter syndrome, that occurs in approximately 1 in 100,000 live male births. It is the most uncommon and complex X and Y chromosomal variation consisting of neurodevelopmental, physical, and medical complications. These boys are at an increased risk for musculoskeletal abnormalities and health difficulties. Intellectual disability, motor deficits, and severe speech dysfunction are common to this population. Specifically, receptive language skills are typically more advanced than expressive language skills, with some individuals being nonverbal. Childhood Apraxia of Speech (CAS) is thought to be the origin of speech and expressive language dysfunction in these boys suggesting that the core challenge is rooted in motor planning deficiency. Challenges in expressive language typically affect all aspects of daily life for males with 49,XXXXY, as it is difficult for them to convey their thoughts and feelings. This often leads to difficulties expressing themselves, social communication challenges, and peer isolation. Males with 49,XXXXY have androgen deficiency that benefits from hormonal replacement therapy (HRT). HRT has been found to have positive effects on neurodevelopmental capabilities in males with 49, XXXXY. Specifically, treated individuals have been found to have improved neurodevelopmental function than the untreated and may therefore have a potential beneficial impact on social skills. Two types of HRT are common during infancy and the childhood years: early hormonal treatment (EHT) and hormonal booster therapy (HBT). EHT is often administered during the “mini-puberty” period, ideally given at 4, 5, and 6 months old, but can be given up until 2 years of age. HBT may be recommended during the school-aged population, often beginning around 5 years old and given up until 11years old. The current study explores the effect of HRT upon expressive and receptive vocabulary skills in males with 49,XXXXY. One hundred and one participants with a diagnosis of 49,XXXXY were evaluated for this study (CA: 88.9 months). Participants completed the Expressive One-Word Picture Vocabulary Test 4th Edition (EOWPVT-4) and the Receptive One-Word Picture Vocabulary Test 4th Edition (ROWPVT-4). Subjects were segregated into four different groups according to their HRT status: no-T, EHT, HBT, and EHT&HBT. EHT consisted of 3 intramuscular injections of 25 mg of testosterone enanthate, once monthly, for three months given between 4 and 24 months of age. HBT consisted of 3 intramuscular injections of 50 mg of testosterone enanthate, once monthly for three months administered between the ages of 5 and 11. Two-tailed t-tests were completed to assess the differences within HRT groups between performance on the EOWPVT-4 and ROWPVT-4. The no-T group (CA: 90.3 months, N = 20) showed a significant difference between EOWPVT-4 and ROWPVT-4 scores (p = .00888) with receptive capabilities being higher than their expressive skills. The EHT group (CA: 79.3 months, N = 44) approached significance with greater skills on the ROWPVT-4 in comparison to the EOWPVT-4 (p = .0556). Finally, the HBT (CA: 104.5 months, N = 8) and EHT&HBT groups (CA: 98.1 months, N = 29) showed no differences between their receptive and expressive capabilities (p = .532; p = .700). The current study expands on the neurocognitive profile of boys with 49,XXXXY and the impact of HRT on their expressive and receptive vocabulary skills. Individuals with 49,XXXXY typically present with severely depressed expressive capabilities in comparison to their receptive skills. The no-T group had this typical presentation with higher receptive language abilities in comparison to expressive capabilities while the EHT, HBT, and EHT&HBT groups showed no differences between receptive and expressive vocabulary skills. Participants who received EHT, HBT, or a combination performed higher on the EOWPVT-4 and presented with commensurate and higher receptive and expressive vocabulary skills than those who had not been treated. These results suggest a positive treatment effect of both EHT and HBT on expressive vocabulary capabilities in boys with 49,XXXXY.