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Page 80 Schmidt et al. J Transl Genet Genom 2024;8:77-84 https://dx.doi.org/10.20517/jtgg.2023.43

RESULTS
Data points were bifurcated into two groups for analysis based on their testosterone status (T or No-T).
Birth data, before the administration of testosterone, was also included. Normative control data for height,
weight, and head circumference was obtained from the World Health Organization’s (WHO) child growth
[16]
standards for boys from birth to 60 months of age . To reduce confounding factors, a biostatistician
blinded to participants’ identities and hormonal treatment statuses completed data analysis.

When comparing head circumference in centimeters, only those from birth to 24 months of age showed a
significant difference between the T group (M = 42.8, P = 0.028) and the No-T group (M = 39.9). The same
finding was true for height in centimeters, T group (M = 67.3, P = 0.047) and the No-T group (M = 62.2).
Comparing weight in kilograms, the birth to 12-month-old (T-group: M = 8.5, P < 0.05; No-T group: 6.4)
and the 13- to 24-month-old (T-group: M = 11.5, P = 0.048; No-T group: M = 13.2) showed significant
differences. There is one noted outlier with a significantly higher weight in comparison to the other subjects
of that age [Figure 1]. This anomaly may be explained by the subject’s family history of increased weight
and size. No significant differences were found between 1.0 years of age and 5 years of age for head
circumference and height [Table 1]. In Figures 1-3, growth curves shown in red and pink reveal typical
childhood growth patterns for all periods. No significant differences were found between 2 and 5 years of
age in weight. All groups showed normalization with their typically developing peers by 5 years of age
[Figures 1-3].

DISCUSSION
Our findings show that EHT does not have a significant effect on growth patterns for boys with 47,XXY
between 2 and 5 years of age. Differences in growth during the infant period (birth-1.0 years) were likely
related to EHT; however, no significant differences were noted between 24-60 months of age in height,
weight, or head circumference. To the best of our knowledge, this is the largest study to analyze growth in
response to HRT in boys with 47,XXY at these ages.

It is important to note that the presented study has some limitations. First, this is not a randomized
controlled trial, and thus we are unable to determine causality. We are also unable to generalize our findings
due to ascertainment bias and a large percentage of individuals who are undiagnosed with 47,XXY. This
specific limitation is a common challenge for all research studies investigating this population.

Potential confounding factors have been minimized for this study. We compared No-T groups and T-
groups and there were no significant differences in maternal or paternal age, birth weight, and parental
educational status [Table 2]. There were five subjects, in both the T and No-T group, with significantly
smaller head circumference measurements in comparison to their same-age peers [Figure 3]. These subjects
had no indications of their neurodevelopmental dysfunction to explain this presentation; however, parental
head circumference was not taken, which could have helped determine if the condition was familial. While
our study investigated height, weight, and head circumference, we did not evaluate body mass index (BMI)
or extremity length. BMI as a measure of growth may have limitations in this population however, as many
of these boys fall into a normal range for BMI at this age.

Previous studies indicate that at birth, males with 47,XXY are smaller in height, weight, and head
circumference than average, and that these children have been shown to accelerate in growth at age three,
and again at the onset of puberty [17-19] . Davis et al. described that a cohort of 20 infants with 47,XXY
[19]
exhibited increased arm span , leg length, and overall stature compared with their typically developing
peers . However, our findings show that after 24 months of age, there is no discernible difference in height,
[20]