ESPE Abstracts

Background: Tall stature is a frequent concern in pediatric endocrine clinics. However, no representative reports addressing etiology and auxological diagnostic cues at specialized healthcare presentation currently exist. We report the etiology of extreme tall stature and describe auxological cues indicative of a growth disorder.

Methods: We identified 145 subjects (girls/boys: 78/67) with extreme tall stature from our institute’s growth database. We applied the criteria: ≥2 measurements with HSDS≥+3 after the age of three years. Subjects born 2012-2018 in the Helsinki University Hospital catchment area with complete medical records were included. We reviewed the medical records, laboratory, genetic, and auxological data. Age at presentation was defined as the first assessment for tall stature in specialized healthcare.

Results: A primary or secondary growth disorder was diagnosed in 64 (44%) children. The frequency of primary growth disorder (girls/boys: 13/21), secondary growth disorders (girls/boys: 21/9), and idiopathic tall stature (ITS) (girls/boys: 44/37) differed between sexes, P=0.03. The most prevalent monogenic syndromes were Sotos (n=5) and Marfan syndromes (n=4). Syndromic tall stature with a neurodevelopmental disorder such as intellectual disability, developmental delay, or autism spectrum disorder lacking a definitive genetic diagnosis was frequent (n=24, 17%) and a male-dominant (67%) phenotype. Molecular genetic studies were relatively frequently used (genetic studies other than karyotype: n=53, 37%) in the diagnostic workup. The most frequent secondary causes were premature adrenarche (n=16) and central precocious puberty (n=9). ITS was diagnosed in 81 (56%) children and was considered mostly non-familial (n=60). Twenty-one subjects with ITS had a tall parent (parental HSDS≥+2). Patients with primary growth disorders presented at a younger age (mean 3.2 years) compared to secondary disorders (mean 5.7 years, P<0.001) and ITS (4.4 years, P=0.021), and patients with secondary causes older than ITS (P=0.014). HSDS (medians 3.1-3.4, P=0.28) or HSDS-TH (medians 2.5-3.1, P=0.18) at presentation did not differ between the groups. Patients with secondary causes had a smaller TH (mean 0.0SD) compared to primary causes and ITS (both, mean 0.7SD, P<0.001), P=0.55 between ITS and primary causes.

Conclusions: We show that primary and secondary growth disorders are frequent in extremely tall children and show sex-specific distribution. Children with extremely tall stature and neurodevelopmental features were prevalent, though a genetic diagnosis was established infrequently in the diagnostic practice. The most functional cues to differentiate the diagnostic groups were age at presentation and TH, whereas HSDS and HSDS-TH did not differ between the groups.