Prevalence of SHOX haploinsufficiency among short statured children.
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.



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.



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.



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.
Department of Growth and Reproduction, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Maja Rou
MR
Marstrand-Joergensen
Department of Growth and Reproduction, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Rikke Beck
RB
Jensen
Department of Clinical Genetics, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Lise
L
Aksglaede
Department of Clinical Genetics, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Morten
M
Duno
Department of Growth and Reproduction, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Anders
A
Juul
D000293:Adolescent; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D006130:Growth Disorders / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D057895:Haploinsufficiency; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D010009:Osteochondrodysplasias / Q000150:complications / Q000453:epidemiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D000074122:Short Stature Homeobox Protein / Q000235:genetics*
C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D019382:Human Growth Hormone