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Exp Clin Endocrinol Diabetes 2021; 129(08): 611-620
DOI: 10.1055/a-1247-4863
Article

Clinical and Genetic Characteristics of 23 Korean Patients with Haploinsufficiency of the Short-stature Homeobox-containing Gene

Jeong-Seon Lee
1   Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s Hospital, Seoul
,
Hwa Young Kim
1   Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s Hospital, Seoul
,
Young-Ah Lee
1   Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s Hospital, Seoul
,
Seong-Young Lee
2   Department of Pediatrics, SMG-SNU Boramae Medical Center, Seoul
,
Tae-Joon Cho
3   Department of Orthopaedics, Seoul National University College of Medicine, Seoul National University Children’s Hospital, Seoul
,
Jung Min Ko
1   Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s Hospital, Seoul
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Abstract

Background The short-stature homeobox-containing gene (SHOX) is one of the major growth genes in humans. The clinical spectrum of SHOX haploinsufficiency ranges from Léri–Weill dyschondrosteosis to idiopathic short stature. Herein, we describe the clinical and genetic characteristics of 23 Korean patients with SHOX deficiency disorders.

Methods Medical records of 23 patients (19 females and 4 males) from 15 unrelated families who were genetically confirmed to have SHOX deficiency were retrospectively reviewed. SHOX gene deletions or mutations were determined by sequence analyses using multiplex ligation-dependent probe amplification, chromosomal microarray, and/or Sanger sequencing methods.

Results In the 15 families, 9 probands were de novo cases. All 23 patients showed mesomelia. Madelung deformity and tibia vara were observed in 13 (56.5%) and 3 (13.1%) patients, respectively. Genetically, 11 (73.3%) of the 15 families showed SHOX deletions of various sizes, and the other 4 families harboured SHOX sequence variants. Four patients had undergone orthopaedic surgeries (3 for tibia vara and 1 for Madelung deformity). Among 7 patients who had received growth hormone treatment for ≥1 year, 5 showed good responses, with a median first-year change-in-height standard deviation score of +0.6. There were no significant differences in the clinical characteristics of the deletion and point mutation groups.

Conclusions A high index of suspicion and the genetic confirmation of SHOX deficiency are helpful for the timely management of the condition and are needed to provide genetic counselling to the family members of the patients.

Key words

SHOX deficiency - Léri-Weill dyschondrosteosis - haploinsufficiency - Madelung deformity - mesomelia


Publication History

Received: 29 April 2020
Received: 14 July 2020

Accepted: 24 August 2020

Article published online:
15 September 2020

© 2020. Thieme. All rights reserved.

© Georg Thieme Verlag KG
Stuttgart · New York

 

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