TY - JOUR

T1 - Prevalence of SHOX haploinsufficiency among short statured children

AU - Marstrand-Joergensen, Maja Rou

AU - Jensen, Rikke Beck

AU - Aksglaede, Lise

AU - Duno, Morten

AU - Juul, Anders

PY - 2017/2

Y1 - 2017/2

N2 - BACKGROUND: The aim of this clinical study was to determine the prevalence of SHOX haploinsufficiency in a population of short stature patients and describe their anthropometric measurements.METHODS: 574 short statured patients were evaluated in a single center (1992-2015). SHOX copy number was detected by quantitative polymerase chain reaction (qPCR) in 574 subjects, followed by multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing in subjects with SHOX haploinsufficiency. We evaluated anthropometric measurements at birth, and at first examination. Skeletal abnormalities were recorded for patients with SHOX haploinsufficiency.RESULTS: Thirty-two patients were excluded due to Turner syndrome (n = 28), SRY-positive 46,XX male karyotype (n = 1), or lacked clinical follow-up information (n = 3). The prevalence of SHOX haploinsufficiency was 9 out of 542 (1.7%). The nine children had decreased height -2.85 (0.6) SD scores (SDS) (mean (SD)) and weight -2.15 (1.36) SDS, P < 0.001 and P = 0.001, respectively. The sitting height/height ratio was increased, P = 0.04. Madelung deformity was diagnosed in three patients. Mean height was -2.9 (0.4) SDS at baseline and increased by 0.25 (0.2) SDS, P = 0.046, after 1 y of growth hormone (GH) treatment.CONCLUSION: The prevalence of SHOX haploinsufficiency was 1.7%. The clinical findings indicating SHOX haploinsufficiency among the nine children were disproportionate short stature and forearm anomalies.

AB - BACKGROUND: The aim of this clinical study was to determine the prevalence of SHOX haploinsufficiency in a population of short stature patients and describe their anthropometric measurements.METHODS: 574 short statured patients were evaluated in a single center (1992-2015). SHOX copy number was detected by quantitative polymerase chain reaction (qPCR) in 574 subjects, followed by multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing in subjects with SHOX haploinsufficiency. We evaluated anthropometric measurements at birth, and at first examination. Skeletal abnormalities were recorded for patients with SHOX haploinsufficiency.RESULTS: Thirty-two patients were excluded due to Turner syndrome (n = 28), SRY-positive 46,XX male karyotype (n = 1), or lacked clinical follow-up information (n = 3). The prevalence of SHOX haploinsufficiency was 9 out of 542 (1.7%). The nine children had decreased height -2.85 (0.6) SD scores (SDS) (mean (SD)) and weight -2.15 (1.36) SDS, P < 0.001 and P = 0.001, respectively. The sitting height/height ratio was increased, P = 0.04. Madelung deformity was diagnosed in three patients. Mean height was -2.9 (0.4) SDS at baseline and increased by 0.25 (0.2) SDS, P = 0.046, after 1 y of growth hormone (GH) treatment.CONCLUSION: The prevalence of SHOX haploinsufficiency was 1.7%. The clinical findings indicating SHOX haploinsufficiency among the nine children were disproportionate short stature and forearm anomalies.

KW - Adolescent

KW - Body Height

KW - Child

KW - Child, Preschool

KW - Female

KW - Gene Deletion

KW - Growth Disorders/complications

KW - Haploinsufficiency

KW - Human Growth Hormone/therapeutic use

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Karyotyping

KW - Male

KW - Osteochondrodysplasias/complications

KW - Point Mutation

KW - Polymerase Chain Reaction

KW - Prevalence

KW - Retrospective Studies

KW - Sequence Analysis, DNA

KW - Short Stature Homeobox Protein/genetics

U2 - 10.1038/pr.2016.233

DO - 10.1038/pr.2016.233

M3 - Journal article

C2 - 27814343

VL - 81

SP - 335

EP - 341

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 2

ER -