Familial, constitutional, and combined idiopathic short stature: longitudinal growth patterns and pubertal effects

Pathological causes account for approximately 15%-20% of short-stature cases, whereas about 80% of short-statured children have no identifiable underlying etiology and are classified as idiopathic short stature (ISS). ISS represents a highly heterogeneous group, and ongoing debates persist due to the limited availability of observational data and advances in genetic research. Despite its high prevalence, long-term auxological data comparing familial, constitutional, and combined variants across pubertal stages remain limited.

Our study aimed to characterize the clinical and laboratory features at presentation and to evaluate the longitudinal growth patterns of children initially diagnosed with ISS.

A retrospective cohort of 171 children with ISS (46.2% female) was analyzed. Participants were classified as prepubertal (Group 1; n = 121) and pubertal (Group 2; n = 50), each further subdivided into familial (a), constitutional (b), and combined (c) subgroups. Anthropometric, familial, and biochemical parameters were assessed at presentation and final follow-up. Standard deviation scores (SDS) were calculated based on national growth references. Intergroup comparisons were performed using ANOVA or the Kruskal-Wallis test with post hoc corrections. Statistical significance was accepted at p < 0.05.

Mean age at first evaluation was 7.94 ± 4.46 years; mean height SDS was -2.45 ± 0.34 with proportionate body proportions and normal birth parameters. Bone age averaged 6.57 ± 4.28 years (≈1.4-year delay). The prepubertal/pubertal distribution was 121 (70.8%) vs. 50 (29.2%); combined phenotypes comprised 53.5% of the cohort. Over 1.85 ± 1.40 years of follow-up, mean ΔHeight SDS was +0.35 ± 0.56; pubertal subgroups, particularly 2b and 2c, showed the most significant gains (ΔHeight SDS +0.58 and +0.53; both p < 0.001 vs. prepubertal). ΔHeight SDS correlated positively with baseline bone-age delay (p < 0.001) and inversely with age (p = 0.002). Growth velocity was normal in all. BMI SDS rose modestly overall (-0.63 ± 0.99 to -0.49 ± 0.92; p = 0.04) and remained below +2 SDS in all cases.

ISS subtypes display distinct auxological courses. Bone-age delay is a key predictor of subsequent catch-up growth, most evident in pubertal CDGP and combined phenotypes. Given the high rate of spontaneous improvement, especially after pubertal onset, careful longitudinal monitoring should precede pharmacologic therapy.