Analysis of growth patterns in Klinefelter syndrome using the QEPS growth model

Anton Holmgren; Aimon Niklasson; Lars Gelander; Andreas Nierop; Aldina Pivodic; Anders Juul; Kerstin Albertsson-Wikland; Lise Aksglaede

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ESPE Abstracts (2024) 98 RFC5.4

ESPE2024 Rapid Free Communications Growth and Syndromes (6 abstracts)

Analysis of growth patterns in Klinefelter syndrome using the QEPS growth model

Anton Holmgren ^1,2,3 , Aimon Niklasson ¹ , Lars Gelander ⁴ , Andreas Nierop ^4,5 , Aldina Pivodic ^6,7 , Anders Juul ^8,9 , Kerstin Albertsson-Wikland ⁴ & Lise Aksglaede ^8,9

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¹GP-GRC, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ²Department of Paediatrics, Halland Hospital, Halmstad, Sweden. ³Department of Research and Development, Region Halland, Halmstad, Sweden. ⁴Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ⁵Muvara bv, Multivariate Analysis of Research Data, Leiderdorp, Netherlands. ⁶APNC, Gothenburg, Sweden. ⁷Department of Ophthalmology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ⁸Department of Growth and Reproduction, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark. ⁹International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

Introduction: Klinefelter syndrome (KS, 47XXY) is the most frequent sex chromosome abnormality in males (prevalence 1/667), with tall stature as one of the key characteristics. We aimed to analyse growth patterns during different growth phases and adult height in KS using the QEPS-model.

Methods: Longitudinal growth-data from 35 boys with KS followed at a tertiary Danish center for paediatric endocrinology were compared with a reference population from GrowUp₁₉₇₄Gothenburg cohort. The QEPS-model describes individual growth from fetal life to adulthood, using four mathematical functions. A quadratic-function (Q) representing basic continuous growth from early fetal life until adult height, a stop-function (S), the exponential function (E) specific for early-life growth and the specific pubertal function (P).

Results: At birth, there were no significant differences between boys with KS and the reference population (Table 1). Compared to reference population, boys with KS had in early-life infancy lower Emax, 63.4 vs 65.1cm, shorter Etimescale (earlier end of E-function), and more basic, continuous Q-function growth, Qmax 111.5 vs 104.1cm. Boys with KS had earlier onset of pubertal growth (AgeP5 11.3/vs 11.8years), 0.5years earlier peak height velocity (AgeTPHV) and equal specific pubertal height gain, Pmax, 17.6 vs 17.4cm. Adult height was 4.1cm higher, 184.6 vs 180.5cm, +0.6SDS vs reference (P = 0.004), and vs parents height difference of +0.7SDS (P <0.0001).

Table 1.
Variable	Klinefelter n = 35	1974-reference n = 1174	p-value Klinefelter vs 1974-reference
Birth weight (g)	3365±607 n = 33	3517±486 n = 1174	0.16
Birth length (cm)	51.0±2.8 n = 32	50.5±2.1 n = 1174	0.36
Mothers height (cm)	167.0±6.0 n = 29	166.8±6.2 n = 892	0.83
Fathers height (cm)	179.3±7.4 n = 29	179.5±6.7 n = 898	0.85
TargetHeight_SDS	-0.07±0.76 n = 29	-0.07±0.71 n = 872	0.99
Emax(cm)	63.4±3.3 n = 35	65.1±2.9 n = 1174	0.0006
Etsc	0.96±0.10 n = 35	1.01±0.09 n = 1174	0.0012
Qmax (cm)	111.5±11.9 n = 35	104.1±8.0 n = 1174	0.0008
Pmax (cm)	17.6±4.5 n = 35	17.4±3.6 n = 1174	0.71
Age P5 (years)	11.3±1.0 n = 35	11.8±1.0 n = 1174	0.0031
Age TPHV (years)	13.2±1.1 n = 35	13.7±1.0 n = 1174	0.0021
Adult height, T_max	184.6±8.2 n = 35	180.5±6.7 n = 1174	0.0004
Data as mean±standard deviation, Mann-Whitney U-test for skewed continuous variables, normally distributed data two-sample t-test.

Conclusion: To our knowledge, this is the first mathematical modelling of growth from birth to adult height for individuals with KS. The prepubertal growth in KS was characterized by a shorter infancy period with less growth, more basic growth during childhood and puberty, resulting in taller adult height.