Neurodevelopmental outcome of prenatally diagnosed boys with 47,XXY (Klinefelter syndrome) and the potential influence of early hormonal therapy.

This cross-sectional study examined the neurodevelopment of a large, prenatally diagnosed population of boys with 47,XXY; investigated the potentially positive effects of early hormonal therapy (EHT) on language, cognition, and motor in this population; and identified novel at risk biomarkers associated with 47,XXY. Two-hundred and seventy two evaluations were collected from 148 prenatally diagnosed boys with 47,XXY between 0 and 36 months and separated into one of three groups, depending on visit age: Y1 (0-12 months; n = 100), Y2 (13-24 months; n = 90), and Y3 (25-36 months; n = 82). Those who received EHT (administered by 12 months) were further separated (Y1, n = 37; Y2, n = 34; Y3, n = 30). Neurodevelopmental evaluations consisted of Preschool Language Scales, Early Language Milestone Scale, and Bayley Scales of Infant and Toddler Development and evaluated the effect of EHT on auditory comprehension, expressive communication, receptive language, cognition, and motor. EHT was found to be associated with a positive effect within the first year of life in these domains, as well as in the second and third year of life. Additionally, three novel at-risk biomarkers were identified in this cohort: feeding difficulties in infancy, positional torticollis, and the need for orthotics. The positive effects of EHT observed in language, cognition, and motor at variable stages within the first 3 years of life provide additional evidence into the possible efficacy of early biological treatment for boys with 47,XXY to address the neurodevelopmental dysfunction.

Positive effects of early androgen therapy on the behavioral phenotype of boys with 47,XXY.

47, XXY occurs in up to 1 in 650 male births and is associated with androgen deficiency, neurodevelopmental delays, and atypical social-behaviors. Previously, we showed that young boys with 47, XXY who received early hormonal therapy (EHT) had significantly improved neurodevelopment. The objective of this follow-up study was to examine the effects of EHT on social behavior in boys with 47, XXY. The study consisted of boys prenatally diagnosed with 47, XXY who were referred for evaluations. Twenty-nine boys received three injections of 25 mg testosterone enanthate and 57 controls did not receive EHT. Behavioral functioning was assessed using the Behavior Rating Inventory of Executive Function, Social Responsiveness Scale, 2nd Ed., and the Child Behavior Checklist for Ages 6-18. The hypothesis that EHT may affect behavior was formulated prior to data collection. Questionnaire data was prospectively obtained and analyzed to test for significance between two groups. Significant differences were identified between group's scores over time in Social Communication (P=0.007), Social Cognition (P=0.006), and Total T-score (P=0.001) on the SRS-2; Initiation (P=0.05) on the BRIEF; and Externalizing Problems (P=0.024), Affective Problems (P=0.05), and Aggressive Behaviors (P=0.031) on the CBCL. This is the third study revealing positive effects of EHT on boys with XXY. There was a significant improvements associated with the 47, XXY genotype in boys who received EHT. Research is underway on the neurobiological mechanisms, and later developmental effects of EHT.

Serotoninergic dysfunction in the 47, XYY syndrome.

In six XYY patients suffering from aggressiveness and admitted by order of law into a security setting for acts of violence, the estimation of cerebrospinal fluid amine metabolites before and after a probenecid test revealed a clear decrease in the turnover of central serotonin (5-HT) while that of dopamine (DA) was unchanged. The treatment with the 5-HT precursor, L-5-hydroxytryptophan (L-5-HTP), in five of the XYYs resulted in a clinical status equivalent to that observed when the patients were previously treated by conventional neuroleptics.