Centro Integrado de Saúde Amaury de Medeiros, Universidade de Pernambuco, Recife, Brazil.
Instituto de Medicina Integral Prof Fernando Figueira, Recife, Brazil.
J Bone Miner Res. 2018 Apr;33(4):753-760. doi: 10.1002/jbmr.3348. Epub 2018 Jan 4.
Osteogenesis imperfecta (OI) is a strikingly heterogeneous group of disorders with a broad range of phenotypic variations. It is also one of the differential diagnoses in bent bone dysplasias along with campomelic dysplasia and thanatophoric dysplasia and can usually be distinguished by decreased bone mineralization and bone fractures. Bent bone dysplasias also include syndromes such as kyphomelic dysplasia (MIM:211350) and mesomelic dysplasia Kozlowski-Reardon (MIM249710), both of which have been under debate regarding whether or not they are a real entity or simply a phenotypic manifestation of another dysplasia including OI. Bruck syndrome type 2 (BRKS2; MIM:609220) is a rare form of autosomal recessive OI caused by biallelic PLOD2 variants and is associated with congenital joint contractures with pterygia. In this report, we present six patients from four families with novel PLOD2 variants. All cases had multiple fractures. Other features ranged from prenatal lethal severe angulation of the long bones as in kyphomelic dysplasia and mesomelic dysplasia Kozlowski-Reardon through classical Bruck syndrome to moderate OI with normal joints. Two siblings with a kyphomelic dysplasia-like phenotype who were stillborn had compound heterozygous variants in PLOD2 (p.Asp585Val and p.Ser166*). One infant who succumbed at age 4 months had a bent bone phenotype phenotypically like skeletal dysplasia Kozlowski-Reardon (with mesomelic shortening, camptodactyly, retrognathia, cleft palate, skin dimples, but also with fractures). He was homozygous for the nonsense variant (p.Trp561*). Two siblings had various degrees of Bruck syndrome caused by the homozygous missense variant, p.His687Arg. Furthermore a boy with a clinical presentation of moderate OI had a possibly pathogenic homozygous variant p.Trp588Cys. Our experience of six patients with biallelic pathogenic variants in PLOD2 expands the phenotypic spectrum in the PLOD2-related phenotypes. © 2017 American Society for Bone and Mineral Research.
成骨不全症（OI）是一组具有广泛表型变异的显著异质性疾病。它也是弯曲骨发育不良的鉴别诊断之一，与卡梅隆发育不良和致死性发育不良有关，通常可以通过骨矿化减少和骨折来区分。弯曲骨发育不良还包括脊柱骨骺发育不良（MIM：211350）和中胚层发育不良 Kozlowski-Reardon（MIM249710）等综合征，两者都存在争议，即它们是否是一个真实的实体，还是仅仅是另一种发育不良（包括 OI）的表型表现。Bruck 综合征 2 型（BRKS2；MIM：609220）是一种由双等位基因 PLOD2 变异引起的罕见常染色体隐性 OI 形式，与先天性关节挛缩伴翼状胬肉有关。在本报告中，我们介绍了来自四个家庭的六名患者，他们具有新的 PLOD2 变异。所有病例均有多处骨折。其他特征从产前致死性严重长骨弯曲，类似于脊柱骨骺发育不良和中胚层发育不良 Kozlowski-Reardon，到经典 Bruck 综合征，再到关节正常的中度 OI。两名有类似 Kyphomelic 发育不良表型的同胞在出生前死亡，他们在 PLOD2 中有复合杂合变异（p.Asp585Val 和 p.Ser166*）。一名在 4 个月大时夭折的婴儿有弯曲骨表型，表型类似于骨骼发育不良 Kozlowski-Reardon（伴有中胚层缩短、爪形手、小下颌、腭裂、皮肤酒窝，但也有骨折）。他是该无义变异（p.Trp561*）的纯合子。两名同胞因纯合错义变异 p.His687Arg 而患有不同程度的 Bruck 综合征。此外，一名具有中度 OI 临床表现的男孩有一个可能致病性的纯合变异 p.Trp588Cys。我们对六名 PLOD2 中双等位基因致病性变异患者的经验扩展了 PLOD2 相关表型的表型谱。
