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SHORT COMMUNICATION

PRENATAL SONOGRAPHIC DIAGNOSIS OFCLEIDOCRANIAL DYSOSTOSIS

1*, 1, 1, 2 . 2

1Centre for Fetal Care, Royal Postgraduate Medical School, Institute of Obstetrics and Gynaecology,Queen Charlotte’s and Chelsea Hospital, London, U.K.

2Kennedy-Galton Centre, Northwick Park and St Marks Hospital Trust, Middlesex, U.K.

Received 11 July 1996Revised 10 December 1996Accepted 6 January 1997

SUMMARY

Cleidocranial dysostosis is an autosomal dominant disorder characterized by absence or hypoplasia of theclavicles, skull abnormalities, and abnormal dentition. The prenatal diagnosis of this condition has been reportedonce previously in a known high-risk pregnancy. In this report we describe the prenatal findings of cleidocranialdysostosis at 19 weeks’ gestation in a woman affected with this disorder but undiagnosed before the fetal scan. Thisreport is unique in the sense that an autosomal dominant condition diagnosed in the fetus led to a similar diagnosisin the mother. ? 1997 by John Wiley & Sons, Ltd.

Prenat. Diagn. 17: 770–772, 1997No. of Figures: 2. No. of Tables: 0. No. of References: 7.

: cleidocranial dysostosis; fetal clavicles; prenatal diagnosis; ultrasonography

INTRODUCTION

Cleidocranial dysostosis is an autosomal domi-nant disorder characterized by abnormal develop-ment of bone and teeth (Jones, 1988). Thissyndrome was first described 100 years ago andmore than 500 cases have been reported so far(Marie and Sainton, 1897; Jones, 1988). The mainclinical features are short stature, partial or com-plete absence of the clavicles, skull hypomineraliz-ation with late ossification of cranial sutures, andabnormal dentition with delayed eruption andirregularities of the teeth. The craniofacial featuresinclude large fontanelles with wide suturesand multiple wormian bones; flat occiput; brachy-cephaly with bossing of frontal, parietal, and

occipital bones; and midfacial hypoplasia with alow nasal bridge. Partial or complete aplasia of theclavicles can be associated with muscular defectsand small thorax with short oblique ribs (Jones,1988).Prenatal diagnosis of cleidocranial dysostosis

has been recently reported in women affected withthis disorder who also had a positive familialhistory (Hamner et al., 1994; Bowerman, 1995). Inthis report we describe the diagnosis of cleido-cranial dysostosis in the fetus which led to a similardiagnosis in the mother.

CASE REPORT

A 26-year-old Caucasian woman, gravida 2 para1, was referred at 19 weeks’ gestation because ofthe prenatal detection of abnormal skull ossifi-cation, short femora, and short humeri during the

*Correspondence to: Jamiyah Hassan, MD, Centre for FetalCare, Queen Charlotte’s and Chelsea Hospital, GoldhawkRoad, London W6 0XG, U.K.

CCC 0197–3851/97/080770–03 $17.50? 1997 by John Wiley & Sons, Ltd.

second-trimester anomaly scan. Her previous preg-nancy was uncomplicated and resulted in a normalspontaneous vaginal delivery of a healthy babygirl. Ultrasonographic examination revealed asingleton fetus in cephalic presentation, a highanterior placenta, and normal amniotic fluid vol-ume. The fetal head and abdominal circumferencemeasurements were appropriate for gestational agebut all long bones were slightly below the fifthcentile (Romero et al., 1988). The fetus had anormal intracranial anatomy but, interestingly, theclavicles were markedly shortened with the rightand left measuring 4 mm and 3·2 mm, respectively(Fig. 1), well below the normal range for 19 weeks’gestation of 15–25 mm (Yarkoni et al., 1985). Therest of the fetal anatomy appeared normal. Thepatient herself had absent clavicles and was able toappose her shoulders (Fig. 2). In addition, she hada short stature, a flat occiput, and midfacial hypo-plasia with abnormal dentition. Her mother wasnormal but she did not know the identity of herfather or her paternal family history. These fea-tures, and those present in the fetus, suggested adiagnosis of cleidocranial dysostosis in both themother and the fetus. Subsequent assessment by aclinical geneticist confirmed the diagnosis in the

mother, and maternal karyotyping demonstrated anormal 46,XX complement with no chromosomerearrangement of chromosome 6, i.e., the locationof the cleidocranial dysostosis gene (Feldmanet al., 1995). After an uncomplicated antenatalcourse, she delivered spontaneously at 40 weeks amale infant weighing 3629 g with Apgar scores of 9and 10 at 1 and 5 min, respectively. Physicalexamination of the infant revealed bilateral mark-edly short clavicles, large fontanelles with widesutures and flat occiput, midfacial hypoplasia, andfrontal bossing, confirming the prenatal diagnosisof cleidocranial dysostosis.

DISCUSSION

Prenatal diagnosis of cleidocranial dysostosis isrelatively simple when there is a known positivefamily history (Hamner et al., 1994; Bowerman,1995). In our case, there was no definite diagnosisin the mother, who had absent clavicles and wasable to appose her shoulders. Because this con-dition does not seriously affect the individual, itfrequently goes unrecognized, as demonstrated byour patient. The markedly short clavicles in the

Fig. 1—Ultrasonographic appearance of the fetal clavicles (arrows) at 19weeks’ gestation showing severe bilateral hypoplasia

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fetus led to the suspicion of an autosomal domi-nant disorder which has affected the mother as wellas the fetus. Even though the subsequent geneticevaluation in the mother showed no rearrange-ment in chromosome 6, we did not check for anymicrodeletion which will not show up on thestandard technique.The most striking prenatal feature of cleido-

cranial dysostosis is the detection of abnormalclavicles, which could range from total absenceto unilateral shortening. In a previous report(Bowerman, 1995), severe bilateral hypoplasticclavicles were present at 15 weeks’ gestation, in

agreement with our case in which the hypoplasticclavicles were detected at 19 weeks. In anotherreport, however, a normal left clavicle was foundat 15 and 20 weeks, but the right clavicle waspoorly developed (Hamner et al., 1994). Otherfindings in congenital cleidocranial dysostosis arenot specific. The detection of short bones andhypomineralization of the skull can also be seen inmany other skeletal dysplasias associated withbone demineralization, which include osteogenesisimperfecta, hypophosphatasia, and heterozygousachondroplasia (Romero et al., 1988; Bowerman,1995). However, in these conditions thedemineralization is generalized with normal cla-vicular size. Therefore, in our case, the presenceof clavicular hypoplasia led to the definitivediagnosis.

REFERENCESBowerman, R.A. (1995). Anomalies of the fetal skeleton;sonographic findings, Am. J. Roentgenol., 164, 973–979.

Feldman, G.J., Robin, N.H., Brueton, L.A., Robertson,E., Thompson, E.M., Siegel-Bartelt, J., Gasser, D.L.,Bailey, L.C., Zackai, E.H., Muenke, M. (1995). Agene for cleidocranial dysplasia maps to the short armof chromosome 6, Am. J. Hum. Genet., 56, 938–943.

Hamner, L.H., Fabbri, E.L., Browne, P.C. (1994). Pre-natal diagnosis of cleidocranial dysostosis, Obstet.Gynecol., 83, 856–857.

Jones, K.L. (1988). Smith’s Recognizable Patterns ofHuman Malformation, 4th edn, Philadelphia: W. B.Saunders, 362–363.

Marie, P., Sainton, P. (1897). Observationd’hydrocephalie hereditaire (pere et fils) par vice dedeveloppement du crane et du cerveau, Bull. Mem.Soc. Med. Hop. (Paris), 14, 706.

Romero, R., Pilu, G., Jeanty, P., Ghidini, A., Hobbins,J.C. (1988). Prenatal Diagnosis of CongenitalAnomalies, CT: Norwalk, Appleton & Lange, 311–314.

Yarkoni, S., Schmidt, W., Jeanty, P., Reece, E.A.,Hobbins, J.C. (1985). Clavicular measurement: a newbiometric parameter for fetal evaluation, J. Ultra-sound Med., 4, 467–470.

Fig. 2—Photograph of the mother showing facial features ofcleidocranial dysostosis and the ability to appose the shoulders.(Print reproduced with permission)

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