North West Thames Regional Genetic Service, London North West Hospitals NHS Trust, Harrow, Middlesex, HA1 3UJ, UK.
Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK.
Eur J Hum Genet. 2018 Sep;26(9):1288-1293. doi: 10.1038/s41431-018-0166-7. Epub 2018 Jun 11.
Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly (MDMHB) is an autosomal-dominant skeletal dysplasia characterised by metaphyseal flaring of the long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, brachydactyly, dental anomalies and mild osteoporosis. To date, only one large French Canadian family and a Finnish woman have been reported with the condition. In both, intragenic duplication encompassing exons 3-5 of the RUNX2 gene was identified. We describe a new, three-generation family with clinical features of MDMHB and an intragenic tandem duplication of RUNX2 exons 3-6. Dental problems were the primary presenting feature in all four affected individuals. We compare the features in our family to those previously reported in MDMHB, review the natural history of this condition and highlight the importance of considering an underlying skeletal dysplasia in patients presenting with significant dental problems and other suggestive features, including disproportionate short stature and/or digital anomalies.
骨干发育不良伴上颌骨发育不全和短指（趾）畸形（MDMHB）是一种常染色体显性骨骼发育不良，其特征为长骨干骺端增宽、锁骨内半增宽、上颌骨发育不全、短指（趾）畸形、牙齿异常和轻度骨质疏松症。迄今为止，仅报道了一个法裔加拿大大家庭和一个芬兰女性患有这种疾病。在这两种情况下，均发现了 RUNX2 基因外显子 3-5 包含的基因内重复。我们描述了一个具有 MDMHB 临床特征的新的三代家族，以及 RUNX2 外显子 3-6 的基因内串联重复。在所有 4 名受影响的个体中，牙齿问题是主要的首发特征。我们将我们家族的特征与先前报道的 MDMHB 进行比较，回顾该疾病的自然病史，并强调在出现明显牙齿问题和其他提示性特征（包括不成比例的身材矮小和/或数字异常）的患者中，考虑潜在骨骼发育不良的重要性。
