Tall Stature: A Challenge for Clinicians

Abstract

Clinicians generally use the term “tall stature” to define a height more than two standard deviations above the mean for age and sex. In most cases, these subjects present with familial tall stature or a constitutional advance of growth which is diagnosed by excluding the other conditions associated with overgrowth. Nevertheless, it is necessary to be able to identify situations in which tall stature or an accelerated growth rate indicate an underlying disorder. A careful physical evaluation allows the classification of tall patients into two groups: those with a normal appearance and those with an abnormal appearance including disproportion or dysmorphism. In the first case, the growth rate has to be evaluated and, if it is normal for age and sex, the subjects may be considered as having familial tall stature or constitutional advance of growth or they may be obese, while if the growth rate is increased, pubertal status and thyroid function should be evaluated. In turn, tall subjects having an abnormal appearance can be divided into proportionate and disproportionate syndromic patients. Before initiating further investigations, the clinician needs to perform both a careful physical examination and growth evaluation. To exclude pathological conditions, the cause of tall stature needs to be considered, although most children are healthy and generally do not require treatment to inhibit growth progression.In particular cases, familial tall stature subject can be treated by inducing puberty early and leading to a complete fusion of the epiphyses, so final height is reached. This review aims to provide proposals about the management of tall children.

Etiology and clinical profile of patients with tall stature: A single-center experience

“…[ 2 ] Tall stature is defined as height more than two standard deviations (SD) above the mean for a given age and gender. [ 3 ] In a normally distributed dataset, mean ± 2 SD values cover about 95.5% of the population studied. Thus, in a given population, around 2.3 percent of individuals are likely to be tall and equal numbers are likely to be short.…”

Large-scale genomic data-mining implicates dysregulated nuclear receptor-mediated signaling in mental illness

“…Notably, > 20% of NTC genes in GWS loci are associated with two or more PDs (e.g., EP300 and ESR2). A similar overlap was seen for non-psychiatric traits whose biology is closely interlinked with NR-mediated signaling [97][98][99][100][101][102][103][104] [Supplementary Table 7].…”

“…While not taking into the account the significant genetic overlap between PDs [5] , these associations remained significant for MDD and BPD even after adjusting for multiple testing by applying a conservative Bonferroni correction [Figure 2]. When we applied the same approach to summary statistics from non-PD GWASs where NR-mediated signaling has been reported to play a role [97][98][99][100][101][102][103][104] , a very significant association was seen for the NR coregulator subset in height and BMI, as well as a moderate significant association of the NR coregulator subset to HF (Supplementary Figure 1; P = 0.002). For COVID-19 (positive vs. population), in which NR biology plays no obvious role, no association was observed [Supplementary Figure 1].…”

The aetiology of extreme tall stature in a screened Finnish paediatric population

“…Tall stature is a common reason for paediatric endocrinologist or clinical geneticist consultation that aims at early detection and treatment of possible underlying primary or secondary pathological causes [1] . Several guidelines on the diagnostic approach to tall stature and accelerated growth have been published [1] , [2] , [3] , [4] , [5] , [6] . The guidelines suggest that children over three years with either height SDS (HSDS) ≥+2.5 [ 1 , 2 , 7 ] or height deviation from target height (HSDS-THSDS) ≥+2 SDS [ 3 , 5 , 6 ], should be evaluated in specialized healthcare.…”

“…Several guidelines on the diagnostic approach to tall stature and accelerated growth have been published [1] , [2] , [3] , [4] , [5] , [6] . The guidelines suggest that children over three years with either height SDS (HSDS) ≥+2.5 [ 1 , 2 , 7 ] or height deviation from target height (HSDS-THSDS) ≥+2 SDS [ 3 , 5 , 6 ], should be evaluated in specialized healthcare. Additionally, the most comprehensive guideline on tall stature, the Dutch national guideline [1] , recommends that molecular genetic studies including whole-exome sequencing (WES) could be considered as a part of the comprehensive diagnostic evaluation in extremely tall children, defined as HSDS ≥+3 from the age and sex specific population mean (i.e.…”