ESPE Abstracts (2022) 95 P1-511

ESPE2022 Poster Category 1 Growth and Syndromes (85 abstracts)

Clinical characterization of patients with SHOX variants regarding their functional classification

Carmen Rodríguez Barrios 1 , Jesús Domínguez Riscart 1,2 , Ana García Zarzuela 1,2 , Paola Arellano Ruis 1 , Karen Heath 3,4,5 & Alfonso M. Lechuga-Sancho 1,2,6


1Hospital Universitario Puerta del Mar, Cádiz, Spain; 2INiBICA, Cádiz, Spain; 3Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ and Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain; 4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain; 5CIBERER, ISCII, Madrid, Spain; 6Departamento Materno Infantil y Radiología, Universidad de Cádiz, Cádiz, Spain

Introduction: Short stature is frequently caused by SHOX variants causing functional deficiency. SHOX resides in the pseudoautosomal region (PAR1) of the sex chromosomes and SHOX/enhancer alterations result in a broad phenotypic range: from Langer mesomelic dysplasia, Léri-Weill dyschondrosteosis to idiopathic short stature (ISS). Growth hormone (GH) therapy is indicated for those individuals with short stature due to SHOXdeficiency. A frequent limitation in molecular studies is the identification of genetic variants of unknown significance (VUS), limiting the access to GH therapy. Our purpose was to compare the clinical characteristics of patients with short stature with pathogenic SHOX variants vs those with VUS.

Methods: Retrospective observational study analyzing the results of SHOX positive genetic studies in patients of our Genetic Unit, Cadiz from 2015-2021. Molecular studies (MLPA, HRM, sequencing) were performed at the Institute of Medical & Molecular Genetics (INGEMM, Madrid). Patients were divided in two groups according to the genetic results: Pathogenic variants vs. VUS. Those with chromosopathies were excluded from the study.

Results: We found 13 patients with SHOX/enhancer alterations (5 deletions, 2 missense variants, and 6 duplications). All duplications were classified as VUS, while the remaining variants were classified as pathogenic. Clinical characteristics are summarized in table 1. Both groups had similar height z-scores. The only difference between groups was sitting height z-scores, which was significantly lower in the VUS group.

Number of patients (n=13) 7 6 -
AGE (years) 10.08 (6.41-13.33) 8.41 (7.00-11.41) 0.617
SEX (male/female) 2/5 4/2 0.170
WEIGHT MEAN, RANGE (SDS) -0.85 (-1.20--0.69) -1.62 (-1.78--1.10) 0.046
HEIGHT MEAN, RANGE (cm) 127.10 (108.40-140.10) 116.40 (110.80-134.30) 0.866
HEIGHT MEAN, RANGE (SDS) -2.18 (-3.04--1.08) -2.3 (-2.61--2.01) 1.000
SITTING HEIGHT (SH) MEAN, RANGE (cm) 68.5 (58.80-75.50) 61.35 (60.90-72.50) 0.474
SH:H (RANGE) 0.55 (0.54-0.56) 0.52 (0.52-0.55) 0.116
SH MEAN, RANGE (SDS) 0.35 (0.27-0.72) -0.07 (-0.26--0.01) 0.032
ARM SPAN (RANGE) 128.60 (107.50-134.30) 122.80 (106.50-143.50) 0.935
ARM SPAN:HEIGHT (RANGE) 1.01 (0.96-1.01) 0.99 (0.96-1.02) 0.850

Conclusions: In our small series, patients with short stature and SHOX duplications (VUS) have a significantly lower sitting height SDS than those with pathogenic variants. No other phenotypic characteristic helped to differentiate between groups. This finding emphasizes the need to analyse larger cohorts, perform functional studies of their genetic variants and/or to continue to search for a different cause to their short stature.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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