Huang Dan, Zhao Jia, Xia Fang-Ling, Zou Chao-Chun
Department of Child Health Care, Hangzhou Women's Hospital (Hangzhou Maternity and Child Care Hospital), Hangzhou 310008,China.
Department of Endocrinology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.
Children (Basel). 2022 Sep 22;9(10):1447. doi: 10.3390/children9101447.
Trichorhinophalangeal syndrome type I (TRPS I; MIM 190350) is a rare autosomal dominant disorder of congenital malformations due to variants of the gene TRPS1. We reported on an 11-year-old Chinese boy with TRPS I. He had typical clinical findings, including sparse hair, a bulbous nose, a long philtrum, a thin upper lip, and skeletal abnormalities including cone-shaped epiphyses, shortening of the phalanges, and short stature. Trio whole exome sequencing identified a likely pathogenic heterozygous variant c.1957C > T (p.Q653*) in exon 4 of TRPS1, which has not been previously reported. He had been treated with rhGH therapy at a dose of 0.34 mg/(kg/week) at age 11, and a follow-up was conducted for one year. The rhGH therapy led to an increase in growth with a mean growth velocity of 1.12 cm/month (+1.1 SDS/year), and insulin-like growth factor 1 (IGF-1) concentration increased within normal range in our case. Moreover, we summarize 12 cases with TRPS I, including TRPS1 gene variants, growth hormone (GH) axis evaluation, IGF-1 concentration, and treatment in each analyzed case. Eight cases with TRPS I show a good response to rhGH therapy, and five of them have elevated IGF-1. Classic GH deficiency is not common among patients with TRPS I. The presence or absence of GH deficiency is not an absolute criterion for determining whether rhGH therapy should be used in TRPS I. It proves that rhGH therapy improves height outcomes before puberty in TRPS I in the short term. Effects on final adult height will need a longer follow-up and more adult-height data. The rise in IGF-1 could correlate with an increase in short-term height. Measuring IGF-1 levels is recommended as part of the assessment during the follow-up of patients with TRPS I.
I型毛发鼻指综合征(TRPS I;MIM 190350)是一种由TRPS1基因突变导致的罕见常染色体显性先天性畸形疾病。我们报告了一名患有TRPS I的11岁中国男孩。他具有典型的临床特征,包括头发稀疏、球状鼻、人中长、上唇薄,以及骨骼异常,如锥形骨骺、指骨缩短和身材矮小。三联体全外显子测序在TRPS1基因第4外显子中鉴定出一个可能致病的杂合变异c.1957C>T(p.Q653*),此前未见报道。他在11岁时接受了重组人生长激素(rhGH)治疗,剂量为0.34mg/(kg/周),并进行了为期一年的随访。rhGH治疗使生长加速,平均生长速度为1.12cm/月(+1.1 SDS/年),且本病例中胰岛素样生长因子1(IGF-1)浓度在正常范围内升高。此外,我们总结了12例TRPS I病例,包括TRPS1基因变异、生长激素(GH)轴评估、IGF-1浓度以及各分析病例的治疗情况。8例TRPS I患者对rhGH治疗反应良好,其中5例IGF-1升高。典型的GH缺乏在TRPS I患者中并不常见。GH缺乏的存在与否并非决定TRPS I患者是否应使用rhGH治疗的绝对标准。这证明rhGH治疗在短期内可改善TRPS I患者青春期前的身高结局。对最终成人身高的影响需要更长时间的随访和更多成人身高数据。IGF-1的升高可能与短期身高增加相关。建议在TRPS I患者随访期间测量IGF-1水平作为评估的一部分。