Social, emotional, and behavioral functioning in adolescents with Klinefelter syndrome

Abstract

Objective

Klinefelter syndrome (KS) is a common genetic condition in males associated with an extra X chromosome (i.e., 47XXY). Individuals with KS often experience androgen insufficiency and tall stature, and are at increased risk for depression, anxiety, and social challenges. This cross-sectional study investigates social and emotional function in 52 boys with KS and 62 typically developing (TD) boys, ages 8–13 years.

Methods

Self-report measures of anxiety, depression, and behavior and parent-report measures of social functioning and behavior were completed. In primary analyses, linear regression was used to test the effect of group (KS, TD) on standardized scores derived from widely used rating scales. In secondary analyses, we explored the influence of pubertal status on these scores, as well as concordance between self- and parent-ratings.

Results

Our Results indicate that boys with KS exhibit significantly increased anxiety, depression, and social difficulties relative to TD peers. Amongst participants with KS, peri-pubertal males generally experienced more difficulties in aspects of social and emotional functioning as compared to pre-pubertal males. Concordance analyses revealed differences between parent- and child-reports.

Conclusion

These findings indicate that alterations in social, emotional, and behavioral function are present in boys and adolescents with KS and may be influenced by puberty.

INTRODUCTION

Klinefelter syndrome (KS), defined by an extra X chromosome (1), is the most common sex chromosome disorder in males, affecting approximately 1 in 600 live births^1,2. Physical characteristics of KS include small testes, tall stature, androgen deficiency, gynecomastia, and azoospermia – although those as well as their pubertal development can vary^3,4. In addition to physical features, KS is associated with a variety of social, emotional, and cognitive challenges^3.. Several studies in adults with KS have documented social engagement problems, including difficulties in communication, social skills, imagination, and attention switching in social environments^3,5,6. These social difficulties place individuals with KS at increased risk for experiencing poor self-esteem, impulsivity, social anxiety and withdrawal, inappropriate behavior, and less accurate perceptions of social-emotional cues^{1, 3, 7, 8, 9}. The social challenges are thought to be a consequence of neurocognitive factors⁷. Specifically, individuals with KS have difficulties in information processing when “social load” increases (e.g., higher-order labeling and interpretation of social cues) and theory of mind (ToM; e.g., attribution of mental states, intentions and emotions to others)⁷. Given that language, literacy, and social-pragmatic deficits are common in KS, early assessment and intervention may reduce the risk for language and literacy problems and improve academic functioning, and thereby reduce social, emotional, and behavioral difficulties throughout the lifespan^5,7,8.

With respect to emotional functioning, adults with KS exhibit increased rates of anxiety and depression. Specifically, Turriff and colleagues (2011)¹ found that over 68% of participants in their sample of 310 adolescents and adults (14–75 years of age) with KS reported clinically significant levels of depressive symptoms. In another study, Tartaglia and colleagues (2010) found that more than 25% of their sample of 57 boys with KS, aged 6 to 21, reported problems with anxiety, depression, and somatic complaints. Despite the significant impact and high prevalence of internalizing disorders in KS, few studies have focused on the determinants and prevalence of mood and anxiety symptoms⁹ before and during the pubertal timeframe. Moreover, to the best of our knowledge, no studies to date have integrated child and parent report of emotional functioning or examined parent-child concordance among individuals with KS specifically.

KS is also associated with androgen insufficiency, a clinical hallmark that typically emerges in mid- to late-puberty¹⁰ that may contribute to social and emotional difficulties. Existing research in typically developing (TD) males underscores the importance of gonadal hormones in the development of affective and social circuits during puberty¹¹. For example, pubertal changes in reward- and approach-related behaviors have been noted in TD males^12,13 and directly linked with changes in circulating testosterone levels^14,15. In line with these findings, emerging work suggests that androgen supplementation, in combination with specific educational, family, and social support, improves behavioral functioning in males with KS¹⁵. Yet, it remains unclear whether social and emotional problems worsen in adolescence in KS, when androgen insufficiency typically begins.

This cross-sectional study was designed to elucidate alterations in social, emotional, and behavioral functioning in children and adolescents with KS relative to TD peers. We compared 52 boys with KS to 62 TD boys (8–13 years of age) on age-normed measures of depression, anxiety, and social functioning. We hypothesized that boys with KS would demonstrate worse social, emotional, and behavioral functioning relative to TD boys. Additional follow-up exploratory analyses sought to determine whether pubertal development was associated with behavior within and between groups. Finally, we explored concordance between parent and child ratings of social and emotional functioning.

METHODS

Participants

Data were collected as part of a larger multisite longitudinal investigation of mood, behavior, cognition, and neurodevelopment in school-aged boys with and without KS at Stanford University School of Medicine, Department of Psychiatry and Biobehavioral Science, California, US and Department of Pediatrics, Division of Endocrinology, Nemours/Alfred I. duPont Hospital for Children, Delaware, US. The data used in this study was collected between 2019 and 2022. Study protocols were carried out in accordance with the latest version of the Declaration of Helsinki and were approved by our Institutional Review Boards. Before participation, informed consent was obtained from one parent/guardian, and informed assent was obtained from each participant. Participants were recruited to be matched based on age and non-verbal IQ as indexed by the Visual Spatial Index from the Wechsler Intelligence Scale for Children, 5^th edition (WISC-V¹⁷). A socio-economic score (SES) score was determined for each participant based on home zip code using U.S. census data as in previous studies¹⁸. Briefly, total family income for each participant was divided by median family income using census data by zip code. Boys with KS were recruited through university- and community-based pediatricians, pediatric endocrinologists, and medical geneticists, as well as through advertisements in local and national chapters of organizations serving individuals with KS and their families. The TD group was recruited through advertisements on internet bulletin boards, schools, parent organizations and social media.

For each participant in the KS group, diagnosis was confirmed by karyotype analysis demonstrating non-mosaic, 47,XXY KS. Out of 52 participants with KS, 13 boys (25%) were under testosterone replacement therapy within the past 4 months. Participants in both groups were excluded if they had history of traumatic brain injury, hypoxic-ischemic encephalopathy, uncontrolled seizure disorder, psychosis, or premature birth (< 32 weeks gestational age). English was the primary language spoken by all participants. A total of 114 participants (N_KS=52, N_TD=62) met inclusion criteria and underwent assessments.

Behavioral assessment

The following child assessments were administered to participants by trained research staff: the Multidimensional Anxiety Scale for Children 2nd edition (MASC-2¹⁹), Children’s Depression Inventory 2nd edition (CDI-2²⁰) and Behavioral Assessment System for Children 3rd edition Self-Report of Personality (BASC-3 SRP²¹). Due to local COVID-19 pandemic-related travel restrictions, a portion of child assessments were conducted remotely via secure video visits (38% of all participants, including 29% of the KS group and 45% of the TD group). Additionally, parents completed the Social Responsiveness Scale, 2nd Edition (SRS-2²²) and the Behavioral Assessment System for Children, 3rd Edition, Parent Rating Scale (BASC-3 PRS²¹) via selfadministration. Some parents completed the rating scales during the childś visit to the lab, whereas other parents did them at home online – parents rating scales were completed within 2 weeks of childś assessment.

Pubertal assessment

A trained physician or physician assistant assessed genital and pubic hair Tanner staging via physical exam²³. Self-report ratings were used in place of physician ratings when a physical exam was not possible (e.g., due to local pandemic-related restrictions that prohibited in person visits, 14.5% and 11.5% of participants in the TD and KS groups, respectively). Genital and pubic hair ratings were averaged to produce mean Tanner scores. As in previous studies by our group²⁴ participants with an average Tanner score of 0 were categorized as pre-pubertal, and participants with an average Tanner score equal to or above 0.5 were categorized as peri-pubertal.

Primary statistical analyses: KS-associated alterations in social, emotional, and behavioral functioning

The Statistical Package for the Social Sciences (SPSS) version 26 was used for statistical analyses²⁵. Data were visually inspected to identify outliers and examine the distribution. Linear regression²⁶ was used to examine potential group differences in age-normed T-scores on each assessment. To reduce multiple comparisons, analyses were restricted to key summary metrics for each assessment (i.e., total score on the CDI-2, MASC-2, and SRS-2; composite scores on the BASC-3 PRS and SRP for the Internalizing Problems, Externalizing Problems, Behavioral Symptoms and Adaptive Skills scales; composite scores on the BASC-3 SRP for the Emotional Symptoms, Inattention/Hyperactivity, Personal Adjustment and School Problems scales). T scores were entered as the dependent variable in step 1 of a hierarchical linear regression, with group (KS, TS) entered as a predictor²⁶.

Secondary exploratory analyses: pubertal associations

Secondary analyses explored the influence of puberty and the interaction of puberty and group on assessment scores by adding dichotomized pubertal group (pre-pubertal, peri-pubertal) in step 2 of the hierarchical linear regression noted above. The interaction between and diagnostic groups were entered as a predictor in step 3.

Secondary exploratory analyses: parent-child concordance

Additional exploratory analyses examined concordance between parent and child ratings of the child’s mood and behavior on the BASC-3. This analysis was restricted to scales of the BASC-3 PRS and BASC-3 SRP that had direct analogs, including Atypicality, Attention Problems, Anxiety, Depression, Somatization, and Hyperactivity. Because data were not normally distributed, bivariate Spearman correlations were conducted within each group (KS and TD) for each scale. Fisher’s r-to-z transformation was used to assess the significance of potential differences in strength of correlations (parent and child ratings) between groups (KS and TD).

RESULTS

Participant characteristics

Demographic and clinical participants characteristics are presented in Table 1. No outliers were detected from visual inspection of the data for each selected assessment. Therefore, data from all participants were included in subsequent analyses. Despite efforts to recruit age-matched groups, boys with KS were slightly but significantly older than TD boys (12.2 ± 2.2 versus 11.0 ± 1.7 years, respectively). Hence age-normed standardized scores (i.e., based on normative data published by test developers for each assessment) were used instead of raw scores for all assessments. Moreover, despite our best effort to match the groups on non-verbal IQ, the two groups differed on VSI scores on the WISC-V (100.7 ± 15.5 versus 106.0 ± 11.2 in the KS and TD groups, respectively).

Table 1.

Participant characteristics

Characteristic	KS group n = 52	TD group n = 62	p value
Age (years; mean± SD)	12.2 ± 2.2	11.0 ± 1.7	< 0.001
SES score (mean / SD)	1.0 (0.5)	1.2 (0.6)	0.230
WISC-V VSI T score (mean / SD)	100.7 (15.5)	106.00 (11.2)	0.040
Timing of diagnosis (n; pre- / postnatal)	27/25	-	-
Pre-pubertal/Pubertal (N)	35 / 67	36 / 58	0.320

Demographic and clinical characteristics for the KS group and TD group. See text for details on the computation of the SES score.

Primary analyses: KS-associated alterations in social, emotional, and behavioral functioning

Findings from our primary analyses of group-differences in self- and parent-reports are presented in Table 2, and Figures 1–3. With respect to self-report measures, there was missing data for one participant on variables of MASC-2, two participants on variables of the CDI-2 Score, and 7 participants on variables of both the BASC-3 SRP and BASP-3 PRS. These data were excluded from the analyses. A significant main effect of group was observed for the CDI-2 (β = 0.220, p = 0.016) and MASC-2 (β = 0.270, p = 0.004), indicating more symptoms of depression and anxiety in the KS group relative to the TD group. Additionally, boys with KS demonstrated significantly higher scores on BASC-3 SRP Emotional Symptoms, Inattention/Hyperactivity, and Internalizing Problems indices, as well as significantly lower scores on the Personal Adjustment index (β =−0.239, p = 0.013), indicating greater emotional and attentional difficulties with lower adaptive functioning in the KS group relative to the TD group.

Table 2.

Mean assessment scores for each group

Measure	KS group n = 52	TD group n = 62	p value
CDI-2 Total Score†	54.10 (11.4) / 33%	49.79 (7.8) / 13%	0.016
MASC-2 Total Score†	57.02 (10.5) / 40%	51.61 (9.0) / 18%	0.005
SRS-2 Total Score†	58.87 (11.3) / 38%	45.77 (5.7) / 2%	<0.001
BASC-3 SRP
Internalizing Problems†	53.55 (12.3) / 33%	47.16 (8.7) / 10%	0.004
Emotional Symptoms†	53.10 (13.0) / 27%	46.66 (8.3) / 7%	0.004
Inattention/Hyperactivity†	55.12 (10.1) / 43%	48.64 (9.3) / 16%	0.003
Personal Adjustment†	47.96 (11.4) / 20%	52.62 (7.5) / 19%	0.026
School Problems†	49.88 (12.8) / 20%	49.40 (10.1) / 17%	0.934
BASC-3 PRS
Internalizing Problems†	58.25 (11.2) / 39%	49.16 (7.6) / 5%	<0.001
Externalizing Problems†	57.67 (9.7) / 41%	50.39 (7.2) / 13%	<0.001
Behavioral Symptoms Index†	59.12 (9.6) / 45%	48.07 (7.0) / 36%	<0.001
Adaptive Skills‡	42.88 (8.2) / 12%	54.80 (7.2) / 36%	<0.001

Mean T scores are presented, with standard deviation in parentheses. Percentage values reflect the proportion of participants within each group having a T score ≥ 60. Scores from 60–69 are considered “At risk” and scores ≥70 are considered “clinically significant.”

^†Higher scores are worse;

^‡Higher scores are better.

Figure 1.

Box plots of behavioral assessment scores for participants with KS and TD participants. CDI-2, MASC-2, SRS-2. *indicates p-value <0.05.

Figure 3.

Box plots of behavioral assessment scores on the BASC-3 PRS. *indicates p-value <0.05.

With respect to parent-report measures, significantly higher scores were observed on the SRS-2 (β = 0.601, p < 0.001) for boys with KS, indicating more social difficulties relative to the TD group. Scores on the BASC-3 PRS Behavioral Symptoms, Externalizing Problems, and Internalizing Problems indices were higher in the KS compared to the TD group (β ‘s> 0.396, p’s<0.001), indicating more internalizing and externalizing symptoms in KS. Significantly lower scores were observed on BASC-3 PRS Adaptive Skills (β = −0.617, sp < 0.001), indicating worse adaptive functioning in KS.

Exploratory analyses: the interaction of diagnosis by puberty status

Results from our exploratory analyses of interaction of diagnosis by puberty status are presented in Figure 4. Our findings indicated a significant interaction of pubertal status by diagnostic group on two (age-normed) scales of the CDI-2: Negative Self-Esteem (t(104) = 2.093, p = 0.039) and Ineffectiveness (t(104) = 2.465, p = 0.039). Although pre-pubertal TD and KS groups were not significantly different on CDI-2 Negative Self-Esteem, peri-pubertal groups showed a significant difference (Cohen’s d = 0.726, p = 0.005). Peri-pubertal boys with KS exhibited higher scores on this subscale compared to peri-pubertal TD boys (pubertal KS: 53.4 ± 10.9, 31% with T scores ≥ 60; pubertal TD: 47.2 ± 4.9, 3% with T scores ≥ 60). This pattern of findings was also present on CDI-2 Ineffectiveness (Cohen’s d = 0.575, p = 0.023; peri-pubertal KS: 54.8 ± 11.3, 38% with T scores ≥ 60; peri-pubertal TD: 49.0 ± 8.5, 12% with T scores ≥ 60;). No other selected measures showed a significant interaction of puberty by group.

Figure 4.

Box plots of scores on the Ineffectiveness and Self-Esteem subscales on the CDI-2, grouped by diagnosis and pubertal status. Lower and upper box boundaries are 25th and 75th percentiles, respectively. The line inside each box represents the median. *indicates p-value <0.05.

Exploratory analyses: parent-child concordance

Within both the KS and TD groups, parent and child ratings were significantly positively correlated for School Problems, Attention Problems, and Anxiety indices (r’s range from 0.36 to 0.91, p’s < 0.05; Table 3). Within the KS group, but not the TD group, parent and child ratings were significantly positively correlated for Depression (r = 0.55, p < 0.001) and overall Internalizing Symptoms (r = 0.39, p = 0.006). Within the TD group only, parent and child ratings were significantly positively associated for Hyperactivity (r = 0.36, p = 0.006).

Table 3.

Parent-child concordance of assessment scores.

BASC-3 Scale	KS group Spearman’s rho	TD group Spearman’s rho	Fisher r-to-z p value
Atypicality	-0.14	0.32*	0.014
Depression	0.55**	0.18	0.024
Internalizing Symptoms	0.39**	0.24	0.390
School Problems	0.91**	0.91**	1.000
Anxiety	0.37**	0.36**	0.952
Attention Problems	0.45**	0.40**	0.749
Hyperactivity	0.24	0.36**	0.497

Spearman’s rho correlation coefficients for BASC-3 PRS and SRP scale scores for the KS group and TD group. Fisher r-to-z-transformation value indicates significance of between-group differences in strength of correlations.

^*indicates p-value <0.05

^**indicates p-value <0.01.

When examining potential between-group differences in concordance using Fisher r-to-z transformations, there was a significant difference between the KS and TD groups in parent-child concordance for Atypicality and Depression subscales (p’s = 0.020). Whereas TD boys’ Atypicality ratings were significantly positively correlated with that of their parents (r = 0.32, p = 0.017), ratings between boys with KS and their parents were not (r = - 0.14, p = 0.342). In addition, within the KS group, but not the TD group, child Depression ratings were significantly positively correlated with that of their parents (r = 0.55, p < 0.001). No significant between-group differences were observed in the strength of parent-child correlations for ratings of Anxiety, Attention Problems, Somatization or Hyperactivity (ps > 0.05).

DISCUSSION

In this cross-sectional study, we examined social, emotional, and behavioral functioning in children and adolescents with KS. While average scores on the CDI-2, MASC-2, and SRS-2 for both groups were within one standard deviation of the normative mean (i.e., relative to the reference sample for each assessment), youth with KS in our study cohort demonstrated significantly increased symptoms of anxiety, depression, and social challenges relative to their TD peers and many had scores in the at-risk range (Table 2). Further, we observed, in exploratory analyses, that some symptoms of depression were more severe in pubertal boys with KS. Taken together, our findings suggest that alterations in social, emotional, and behavioral functioning are present in childhood among males with KS and may worsen over the course of pubertal development.

Our results add to previous research showing an increased risk for significant behavioral problems in boys with KS⁵ as well as studies in adults with KS, which note heightened anxiety and depressive symptoms in this population^{27, 28}. In one study, Bouw²⁹ found that one year old boys with KS had difficulties in acquiring social emotional milestones, findings that suggest that KS impact the maturation of the social brain from a very early age on. These findings highlight the need for regular screening of social-emotional symptoms in individuals with KS as well as the importance of early monitoring and anticipatory guidance on appropriate interventions through genetic counselling. Such screening would facilitate the identification of boys who could benefit from mental health services to improve social-emotional function and prevent worsening of symptoms that may negatively impact long-term outcome.

The present study also explored parent-child concordance of assessment scores to clarify if the association between parent and child ratings of the child’s social, emotional, and behavioral functioning varied as a function of group. Overall, boys and their parents showed similar reporting on most scales (i.e., positive correlations ranging from 0.36 to 0.91). By contrast, previous research has generally found low to moderate correlations (i.e., r’s ranging from 0.14 to 0.25) between parent-child concordance rate of social emotional symptoms in typically developing children and adolescents^{30, 31}. Of note, the KS and TD groups in our study showed significantly different levels of parent-child concordance for Depression and Atypicality scales of the BASC-3. Specifically, boys with KS and their parents endorsed comparable levels of depressive symptoms in the child, with a stronger positive correlation than what has previously been reported in other clinical populations^30,31. A possible explanation for this finding is that higher levels of depressive symptoms in boys with KS may lead to elevated awareness and recognition by both the child and the parent. Alternatively, parents of boys with KS may be more vigilant to symptoms.

On measures of Atypicality (the child is not performing at age level development typical of his peer group as determined by medical and development testing), parent and child reports were significantly positively correlated in the TD group, but not the KS group. Higher parent ratings of symptoms assessed in this subscale were linked to higher child self-ratings of the same behaviors in the TD group only. Although not statistically significant, there was a slight negative correlation between parent-child Atypicality ratings in the KS group. This may suggest that boys with KS may have less insight into their behavior in this domain related to odd and unusual behavior. Since autism spectrum disorder (ASD) rates in boys with KS are up to six times more common compared to matched population controls³², a potential cause might include traits associated with ASD such as unawareness of surroundings as well as poor self-insight. Such patterns would highlight the importance of including both parent and child ratings of social-emotional functioning for individuals with KS in clinical settings.

Secondarily, we sought to explore whether symptoms of depression, anxiety, and social dysfunction in males with KS worsen with the onset of puberty, when the first signs of gonadal alterations emerge. Extant work on pubertal development suggests that males with KS typically initiate puberty at the same time as their TD peers, with an initial enlargement of the testes, increase in pubic hair, and rise in testosterone to the low pubertal range⁴. By mid-puberty, however, LH and FSH levels increase to above-normal levels in boys with KS, testosterone slightly declines and testes volume fails to grow³³.

In the current study, we found that although pre-pubertal TD and KS groups did not differ with respect to scores on the CDI-2 Negative Self-Esteem factor, peri-pubertal KS and TD groups did, with the KS group showing higher (more severe) scores on this measure. The same pattern was present for CDI-2 Ineffectiveness. These findings complement findings from researchers who found that pubertal boys with KS presented higher symptoms of social anxiety, as indicated by higher scores on the social skills scale of the Social Anxiety Scale in comparison to TD boys³⁴. Future longitudinal studies that examine the association of social-emotional functioning with testosterone levels as well as the potential impact of testosterone supplementation on depression, anxiety, and social functioning in KS are warranted.

While our findings might imply that perturbed pubertal processes in KS play a role in the onset of social and emotional alterations observed in our KS cohort, we cannot exclude the potential involvement of genetic factors³⁵. Although genomic imprinting effects on social behavior in KS are not fully understood, existing work suggests that parental origin of the extra X chromosome may affect some phenotypic characteristics of KS³⁵. Other research postulates that genes that escape X-chromosome inactivation, leading to over expression of X-linked genes, likely contribute to the KS phenotype³⁵. In support of this finding, the results of the present study mirror the increased prevalence of anxiety, depression, and social challenges found in other aneuploidies involving the X chromosome, such as Turner and Triple X³⁶. Whether KS-associated alterations of brain regions subserving social-emotional functioning (e.g., the amygdala, insula, and ventral prefrontal cortex⁸) also contribute to the behavioral phenotype associated with KS remains to be clarified.

There are a few limitations to the present study. First, approximately half (49%) of our participants were diagnosed with KS postnatally. It is possible, therefore, that ascertainment bias may influence our findings. Previous research has found better outcomes for prenatally (compared to postnatally) diagnosed children with sex choromosome aneuploidy, such as KS³⁷. It is speculated that children with KS who are diagnosed postnatally may be brought in by caregivers seeking a diagnosis as a result of behavioral challenges whereas children who are diagnosed prenatally may have little to no behavioral difficulties due to increased opportunities for early intervention. Exploratory analyses of the current study indicated that although no significant differences were present between KS participants diagnosed pre- versus postnatally for a majority of assessments, a postnatal diagnosis was associated with significantly higher scores on the SRS-2 (p < 0.001; postnatal mean, 65.0 ± 9.5; prenatal mean, 53.8 ± 10.7) and on the BASC-3 PRS Behavioral Symptoms Index (p = 0.050; postnatal mean, 61.8 ± 8.6; prenatal mean, 56.3 ± 10.4). Thus, our findings should be interpreted in light of these differences.

Second, because the present study is cross-sectional (e.g., we examined pre-pubertal vs. peri-pubertal groups), future longitudinal investigations are needed to clarify the relationship between pubertal development and emotional, social, and behavioral functioning over time. Third, participants in the TD group were recruited from local areas near our two research sites. Although substantial efforts to collect a diverse sample were made, there may be geographic biases in the behavioral and cognitive profiles, potentially reducing the generalizability of our findings to the general population. On a last note, participants who were born prematurely (< 32 weeks gestational age) were excluded from the study. However moderate-to late preterm infants (32 to 37 weeks of gestation) were included (10 participants (5%)). Future research should explore whether or notgestational age at birth is a factor associated with social, emotional, and behavioral functioning in KS³⁸. Participants with uncontrolled seizures were also excluded., However, it is important to note that even in those who are seizure free, there can be significant long-term impact in psychosocial functioning³⁹.

In conclusion, in this cross-sectional study, we observed significantly worse social, emotional, and behavioral functioning among boys with KS relative to their TD peers. Exploratory analyses indicated that depressive symptoms may be more severe in boys with KS during the adolescent pubertal interval. Moreover, we found that parent-child concordance on some scales varied by group. Whereas parent and child reports were positively correlated for BASC-3 Atypicality in the TD group only, parent and child reports were positively correlated for BASC-3 Depression in the KS group only. Overall, these findings indicate that social, emotional, and behavioral difficulties in males with KS originate early in life and may worsen in adolescence. Moreover, these findings underscore the importance of eliciting both parent and child input when evaluating social, emotional, and behavioral functioning among boys with KS. Future longitudinal studies with larger samples and more detailed assessments of pubertal development aimed at examining whether patterns of social and emotional change as a function of testosterone level are warranted

Figure 2.

Box plots of behavioral assessment scores on the BASC-3 SRP. *indicates p-value <0.05.

Data availability

The data supporting the conclusions of this article are included within the article. No other sources have been used. Any queries regarding these data may be directed to the corresponding author.