Clinical Manifestations and Outcomes of 20 Korean Hypochondroplasia Patients with the FGFR3 N540K variant.

IF 1.6 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM
Hwa Young Kim, Young Ah Lee, Choong Ho Shin, Tae-Joon Cho, Jung Min Ko
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引用次数: 0

Abstract

Background: Hypochondroplasia is a skeletal dysplasia caused by activating pathologic variants of FGFR3. The N540K variant accounts for 60-70% of reported cases and is associated with severe manifestations. Here, we analyze the clinical manifestations and outcomes of Korean patients with hypochondroplasia harboring the FGFR3 N540K variant.

Methods: Medical records of 20 unrelated patients with genetically confirmed N540K-related hypochondroplasia were retrospectively reviewed. All individuals were diagnosed with hypochondroplasia by Sanger sequencing for FGFR3, or target-panel sequencing for skeletal dysplasia. The effectiveness of growth hormone therapy was analyzed in 16 patients treated with growth hormones.

Results: Among 20 patients (7 men, 13 women), the mean age at first visit was 3.5±1.0 years, and the mean follow-up duration was 6.8±0.6 years. The patients presented with a short stature and/or short limbs. Genu varum, macrocephaly, and developmental delay were observed in 11 (55.0%), 9 (45.0%), and 5 (25.0%) patients, respectively. Of the 12 patients who underwent neuroimaging, five (41.7%) showed abnormal findings (one required operation for obstructive hydrocephalus). Among 16 growth-hormone-treated patients (two were growth-hormone deficient), the increase in height standard deviation scores was significant after a mean 5.4±0.7 years of treatment (+0.6 and+1.8 using growth references for healthy controls and achondroplasia children, respectively). Four patients underwent surgical limb lengthening at a mean age of 8.8±3.3 years.

Conclusions: Neurodevelopmental abnormalities are frequently observed in patients with N540K-related hypochondroplasia. Close monitoring of skeletal manifestations and neurodevelopmental status is necessary for hypochondroplasia.

20例韩国FGFR3 N540K变异软骨发育不良患者的临床表现和预后
背景:软骨发育不良是一种由FGFR3的病理变异激活引起的骨骼发育不良。N540K变异占报告病例的60-70%,并与严重症状相关。在这里,我们分析了韩国携带FGFR3 N540K变异的软骨发育不全患者的临床表现和结局。方法:回顾性分析20例基因证实为n540k相关性软骨发育不全患者的病历。通过FGFR3的Sanger测序或骨骼发育不良的靶板测序,所有个体都被诊断为软骨发育不良。对16例接受生长激素治疗的患者进行生长激素治疗效果分析。结果:20例患者(男性7例,女性13例),平均初诊年龄3.5±1.0岁,平均随访时间6.8±0.6年。患者表现为身材矮小和/或四肢短小。膝内翻11例(55.0%),大头畸形9例(45.0%),发育迟缓5例(25.0%)。在12例接受神经影像学检查的患者中,5例(41.7%)出现异常(1例因梗阻性脑积水需要手术)。在16名接受生长激素治疗的患者(2名生长激素缺乏)中,平均治疗5.4±0.7年后,身高标准差得分显著增加(健康对照和软骨发育不全儿童的生长参考分别为+0.6和+1.8)。4例患者接受手术延长肢体,平均年龄8.8±3.3岁。结论:神经发育异常常见于n540k相关性软骨发育不良患者。密切监测骨骼表现和神经发育状态是必要的软骨发育不良。
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来源期刊
CiteScore
4.10
自引率
5.60%
发文量
72
审稿时长
3 months
期刊介绍: Publishing outstanding articles from all fields of endocrinology and diabetology, from molecular biology to clinical research, this journal is a brilliant resource. Since being published in English in 1983, the popularity of this journal has grown steadily, reflecting the importance of this publication within its field. Original contributions and short communications appear in each issue along with reviews addressing current topics. In addition, supplementary issues are published each year presenting abstracts or proceedings of national and international scientific meetings. The journal was initially published in German and is still the oldest endocrinological periodical in the German-language market!
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