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Acampomelic campomelic dysplasia in genetic male without sex reversal

Journal of Perinatology volume 32, pages 75–77 (2012)Cite this article

The radiographic findings of micrognathia, hypoplastic scapulae, lateral clavicular hooks, absent thoracic pedicles, bilateral anterior radial head dislocations and small vertical ilia are those of autosomal dominant campomelic dysplasia (CD).1, 2 CD was originally described in 1971 by Marouteaux. He chose that name believing that the bowed, short femora and tibiae that occurred in his initially reported patients were an obligatory, integral feature of the syndrome. However, bowed bones are a variable feature of the syndrome.3, 4 The somewhat paradoxical name of acampomelic CD has been given to patients similar to the one described here.3 Typical radiographic features of CD are microcephaly, micrognathia, cleft palate (Pierre Robin sequence), hypoplastic scapulae, non-mineralized thoracic pedicles, small vertical ilia, cervical kyphosis, vertebral anomalies, especially vertebral hypoplasia with resultant kyphoscoliosis, radial head dislocation, anteriorly bowed short tibiae with overlying soft-tissue dimpling, anteriorly bowed femora, short fibulae, lateral clavicular hooks, 11 pairs or ribs and club feet. Other features include hypertelorism, flat nasal bridge, low-set ears, tracheomalacia and complete sex reversal in two thirds of affected genetic males.2, 3, 4 There is a very high perinatal mortality in patients with CD who have severe respiratory distress and CD is even considered to be a lethal skeletal dysplasia.2, 5 However, there are patients who survived beyond infancy. The development of gonadoblastoma has been reported in longer-time survivors with complete sex reversal.6

Most patients with CD have mutations in the SOX9 gene, chromosome 17q 24.3-q25.1. The sex-determining region of chromosome Y or SRY gene is the determinant of testicular development. Any transcription factor that has more than 60% similarity to the DNA-binding motif of SRY is called a SOX gene.7 SOX9 is a transcription factor which has a role in the production of type 2 collagen and in the production of anti-Mullerian hormone or Mullerian-inhibiting factor in male Sertoli cells.4, 5 Abnormal development of the type 2 collagen may account for the skeletal dysplasia, and the role in Mullerian-inhibiting factor production, which may account for the 75% incidence of complete sex reversal in XY patients with CD.4, 5, 6, 7 Interestingly, no SOX 9 mutations were identified in this patient. However, it is known that regulation of the SOX9 gene is complex and mutations distant to this gene may lead to CD.8

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  1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA

    T E Herman & M J Siegel

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  1. T E Herman
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Correspondence to T E Herman.

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Herman, T., Siegel, M. Acampomelic campomelic dysplasia in genetic male without sex reversal. J Perinatol 32, 75–77 (2012). https://doi.org/10.1038/jp.2011.92

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