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Case Reports
. 2018 Sep;26(9):1288-1293.
doi: 10.1038/s41431-018-0166-7. Epub 2018 Jun 11.

A three-generation family with metaphyseal dysplasia, maxillary hypoplasia and brachydactyly (MDMHB) due to intragenic RUNX2 duplication

Amina Al-Yassin  1 , Alistair D Calder  2 , Mike Harrison  3 , Tracy Lester  4 , Helen Lord  4 , Michael Oldridge  4 , Sophie Watkins  3 , Richard Keen  5 , Emma L Wakeling  6
Affiliations
Case Reports

A three-generation family with metaphyseal dysplasia, maxillary hypoplasia and brachydactyly (MDMHB) due to intragenic RUNX2 duplication

Amina Al-Yassin et al. Eur J Hum Genet. 2018 Sep.

Abstract

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Clinical features in the proband (a), her mother (b) and grandmother (c). Maxillary hypoplasia can be seen in all three individuals; the proband and her mother both have hypertelorism; brachydactyly is present in the proband
Fig. 2
Fig. 2
Radiographic findings in proband, aged 27 years. a Postero-anterior chest radiograph. The clavicles are broadened, particularly medially (arrows), with mild broadening of the ribs. b Lateral skull radiograph. There is supraorbital ridging (arrow), an unusual finding in a female. The posterior skull vault is thickened with a prominent external occipital protuberance. Multiple dental crowns are noted. c Lateral lumbar spine radiograph. There are compression fractures of T11, L1, L2 and L3. There is an osteopenic appearance. d Antero-posterior radiograph of both knees. There is undermodelling of the lower femoral metaphyses. e Dorso-palmar radiograph of both hands. There is moderate shortening of the distal phalanges of both thumbs and the middle phalanges of the index and little fingers bilaterally There is milder shortening of the distal phalanges of the index through little fingers. The left fifth metacarpal is also short
Fig. 3
Fig. 3
Dental findings in the proband. a Dental frontal view. b Mandibular arch view. c Dental pantomogram
Fig. 4
Fig. 4
Schematic of 521 amino acid wild-type RUNX2 protein (upper panel) and predicted mutant protein after duplication of exons 3–6 (lower panel). Numbers above the domain structures show the coding exons 2–9. Brackets show the duplicated region. Arrows below show the position of primers designed to PCR across the duplication (exon 6/3). Domains shown: QA poly Glu/poly Ala domain, RHD Runt homology domain, NLS nuclear localisation signal, PST proline-/serine-/threonine-rich domain
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References

    1. Halal F, Picard JL, Raymond‐Tremblay D, de Bosset P, Opitz JM. Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly. Am J Med Genet. 1982;13:71–9. doi: 10.1002/ajmg.1320130112. - DOI - PubMed
    1. Moffatt P, Amor MB, Glorieux FH, et al. Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is caused by a duplication in RUNX2. Am J Hum Genet. 2013;92:252–8. doi: 10.1016/j.ajhg.2012.12.001. - DOI - PMC - PubMed
    1. Avela K, Hirvinen H, Amor MB, Rauch F. Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly in a Finnish woman: first confirmation of a duplication in RUNX2 as pathogenic variant. Eur J Med Genet. 2014;57:617–20. doi: 10.1016/j.ejmg.2014.09.010. - DOI - PubMed
    1. Stein GS, Lain JB, van Wijen AJ, et al. Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression. Oncogene. 2004;23:4315–29. doi: 10.1038/sj.onc.1207676. - DOI - PubMed
    1. Zhang YD, Chen Z, Song YQ, Liu C, Chen YP. Making a tooth: growth factors, transcription factors and stem cells. Cell Res. 2005;15:301–16. doi: 10.1038/sj.cr.7290299. - DOI - PubMed

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