Klemetti P, Valta H, Kostjukovits S, Taskinen M, Toiviainen-Salo S, Mäkitie O
Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland.
Clin Genet. 2017 Aug;92(2):204-207. doi: 10.1111/cge.12969. Epub 2017 Mar 19.
The manifestations of cartilage-hair hypoplasia (CHH), a metaphyseal chondrodysplasia caused by RMRP mutations, include short stature, hypoplastic hair, immunodeficiency and increased risk of malignancies. Clinical features show significant variability. We report a patient with normal height until age 12.5 years (-1.6 SDS at 11 years) who was diagnosed with CHH at 14 years. RMRP sequencing revealed compound heterozygosity for g.70A>G mutation and a 10-nucleotide duplication at position -13 (TACTCTGTGA). Through the Finnish Skeletal Dysplasia Register, we identified 3 additional patients with identical genotype. Two of them also showed unusually mild growth failure (height SDS -1.6 at 14 years and -3.0 at 12 years, respectively). Three of the 4 patients suffered from recurrent infections; 1 developed progressive bronchiectasis and another died from aggressive lymphoma. Our findings expand the phenotypic variability in CHH to include normal childhood height. The milder growth retardation related to this particular genotype was not associated with less severe extra-skeletal manifestations, emphasizing the need for careful follow-up also in CHH patients with mild-skeletal manifestations.
软骨毛发发育不全（CHH）是一种由RMRP突变引起的干骺端软骨发育异常，其表现包括身材矮小、毛发发育不全、免疫缺陷和恶性肿瘤风险增加。临床特征显示出显著的变异性。我们报告了一名患者，在12.5岁之前身高正常（11岁时身高标准差为-1.6），14岁时被诊断为CHH。RMRP测序显示g.70A>G突变和-13位（TACTCTGTGA）的10个核苷酸重复的复合杂合性。通过芬兰骨骼发育异常登记处，我们又确定了3名具有相同基因型的患者。其中两名患者也表现出异常轻微的生长发育迟缓（分别在14岁时身高标准差为-1.6，12岁时为-3.0）。4名患者中有3名患有反复感染；1名发展为进行性支气管扩张，另一名死于侵袭性淋巴瘤。我们的研究结果扩大了CHH的表型变异性，包括儿童期身高正常。与这种特定基因型相关的较轻生长发育迟缓与骨骼外表现较轻无关，强调了对骨骼表现轻微的CHH患者也需要进行仔细随访。
