The Sitting Height/Height Ratio for Age in Healthy and Short Individuals and Its Potential Role in Selecting Short Children for <b><i>SHOX</i></b> Analysis

Abstract

Aims: To determine the presence of abnormal body proportion, assessed by sitting height/height ratio for age and sex (SH/H SDS) in healthy and short individuals, and to estimate its role in selecting short children for SHOX analysis. Methods: Height, sitting height and weight were evaluated in 1,771 healthy children, 128 children with idiopathic short stature (ISS), 58 individuals with SHOX defects (SHOX-D) and 193 females with Turner syndrome (TS). Results: The frequency of abnormal body proportion, defined as SH/H SDS >2, in ISS children was 16.4% (95% CI 10-22%), which was higher than in controls (1.4%, 95% CI 0.8-1.9%, p < 0.001). The SHOX gene was evaluated in all disproportionate ISS children and defects in this gene were observed in 19%. Among patients with SHOX-D, 88% of children (95% CI 75-100%) and 96% of adults had body disproportion. In contrast, SH/H SDS >2 were less common in children (48%, 95% CI 37-59%) and in adults (28%, 95% CI 20-36%) with TS. Conclusion: Abnormal body proportions were observed in almost all individuals with SHOX-D, 50% of females with TS and 16% of children considered ISS. Defects in SHOX gene were identified in 19% of ISS children with SH/H SDS >2, suggesting that SH/H SDS is a useful tool to select children for undergoing SHOX molecular studies.

Role of the Natriuretic Peptide System in Normal Growth and Growth Disorders

“…A great variability in the degree of height deficit was observed among carriers of NPR2 mutation, including relatives of patients with AMDM (height SDS ranged from -4.5 to -1.3). A similar situation was observed in patients with mutations in SHOX gene (OMIM 312865) [44], a well-established cause of short stature. Interestingly, 4 patients (3 Brazilian and 1 Japanese) with heterozygous NPR2 mutations were treated with recombinant human growth hormone.…”

Referencias argentinas para la evaluación de proporciones corporales desde el nacimiento hasta los 17 años

“…En este sentido, la presencia de alteración de las proporciones corporales es un signo utilizado para el estudio de niños con baja estatura sin causa clara. 10 Cabe señalar algunas limitaciones de este trabajo, como el menor número de datos entre el nacimiento y los 3 años de edad, lo que no impidió lograr un buen ajuste de los datos. Otra limitación es que, en la muestra, no están representadas todas las regiones del país, donde variaciones en la composición genética de la población pueden incidir en las proporciones corporales.…”

“…En otras, sin embargo, se necesita de un seguimiento a largo plazo, inclusive hasta la etapa final de crecimiento, momento en el cual los signos clínicos y/o radiológicos son evidentes. [3][4][5][6][7][8][9][10] Muchos niños con DE tienen PC normal para la edad (ent re ± 2 puntuaciones Z) pero clínicamente "alto" para su estatura. El término macrocefalia relativa se utiliza en los casos en los que el PC es normal para la edad y el sexo pero "elevado" para la estatura.…”

Argentine references for the assessment of body proportions from birth to 17 years of age

“…In this study, abnormal body proportions are a sign used to evaluate children with short stature without a clear cause. 10 It is necessary to note certain limitations of this study, such as the lower number of data between birth and age 3, which did not allow the proper adjustment of data. Another limitation is that the sample is not representative of all regions in Argentina.…”

“…By this time, clinical and/or radiological signs are evident. [3][4][5][6][7][8][9][10] Many patients with SD have a HC that is normal for their age (between ± 2 Z-scores), but clinically "large" for their height. The term relative macrocephaly is used for cases in whom head circumference is normal for a given age and sex, but "high" for their height.…”