American J o u r n a l of Medical Genetics 35:69-74 (1990)

Somatic Development in Cleidocranial Dysplasia Birgit Leth Jensen T h e Royal Dental College, Copenhagen, Denmark

As part of a more comprehensive investigation of general and craniofacial development in cleidocranial dysplasia (CCD), the present study describes general somatic development and analyzes longitudinal growth of 17 patients (seven males, ten females, aged 5-46 years) with CCD. Eleven were followed longitudinally. Data included family history, anthropometric measurements, and radiographs of the right hand and forearm. Height and radius length were significantly decreased, being most pronounced in females. The longitudinal growth data showed growth retardation and slightly retarded skeletal maturity throughout childhood. Metacarpophalangeal pattern profile analysis demonstrated great variation in bone lengths, presumably resulting from extra epiphyses in the 2nd and 5th metacarpals and from multiple cone-shaped epiphyses. Findings of the present study support the view that CCD is a generalized skeletal dysplasia.

KEY WORDS: stature, skeletal maturity, head circumference, metacarpophalangeal pattern profile, hand bone dysostoses, autosomal dominant inheritance

INTRODUCTION Cleidocranial dysplasia (CCD)is an autosomal dominant, generalized skeletal disorder characterized by aplasia or hypoplasia of the clavicles, enlarged calvaria with frontal bossing, multiple Wormian bones, delayed tooth eruption, supernumerary unerupted teeth, distal phalanges with abnormally pointed tufts, hypoplasia of the pelvis, and many other abnormalities. One of the most fascinating aspects of the disorder is the generalized failure of midline ossification resulting in Received for publication January 16, 1989; revision received June 29, 1989. Address reprint requests to Birgit Leth Jensen, Royal Dental College, 20 Ngirre Alle, DK-2200 Copenhagen N, Denmark.

0 1990 Wiley-Liss, Inc.

patent anterior fontanelle, persistent metopic suture, nasal bone deficiency,non-union of the mandibular symphysis, bipartite hyoid bone, spina bifida occulta of the cervical, thoracic, or lumbar region, and delayed closure of the pelvic symphysis. The condition, which is well known and reviewed by many authors [Anspach and Huepel, 1935; Lasker, 1946; Herndon, 1951; Andra, 1960; Jarvis and Keats, 19741, was described as early as 1766 by Morand ([Morand, 17661, original work not consulted) and named cleidocranial dysostosis in 1898 by Marie and Sainton [Marie and Sainton, 18981. Because the disorder is now recognized as a generalized disorder of bone, it has been renamed cleidocranial dysplasia [Rimoin, 19781. The present study is part of a more comprehensive investigation of CCD. Previously, we have reported a detailed analysis of abnormalities found in the cranial base [Kreiborg et al., 19811. The purpose of the present paper is t o quantitate generalized somatic development in CCD. Although most of the abnormalities discussed in this paper have been described previously [Hultkrantz, 1908; Paltauf, 1912; Kalliala and Taskinen, 19621, metric and longitudinal studies have been uncommon [Davis, 1974; Kreiborg et al., 19811. MATERIALS AND METHODS The patient population consists of 17 white patients (seven males, ten females) with CCD ascertained through the Institutes of Pediatric Dentistry and of Orthodontics at the Royal Dental College in Copenhagen. The number of examinations, the ages at which they were carried out, and the sex of each patient are summarized in Table I. The total number of observations was 137, and the average number of observations per patient was eight with a range of one to 21. Pedigrees for ten probands are shown in Figure 1. They account for 14 of the 17 patients. Information was not available for the other three patients. Stature was documented for 15 patients. Longitudinal data, available for ten of these patients and totaling 103 observations, were compared with Danish curves for stature [Helm et al., 19781. Head circumference (OFC) was measured in 12 adults [six males, six females] and compared with Danish normative data [Solow, 1966; Ingerslev and Solow, 19753. Other data were derived from standardized radiographs of the right hand and forearm [Solow, 19661. The length of the radius was measured according to the

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TABLE I. Chronological Age of CCD Patients a t Time of Examination Cleidocrania dvsdasia-SamDle

No. 1 2 3 4 5 6

7 8 9 10 11 12 13 14 15 16 17

ID

S

0107 F 0345 M 1065 M 1513 F 2760 M 2784 F 3425 F 5073 F 5731 M 5739 F 5740 F 5741 F 5901 M 6907 F 9153 M 9154 M "9153 F

Age in years Indications of age at examination for each individual

method of Helm et al. [1978], and their normative data were used for comparison. Skeletal maturation was assessed in growing patients by the Tanner-Whitehouse (TW2) method [Tanner et al., 19751. The radius-ulnaA

small bones (RUS) maturation score was calculated for 11patients (fivemales, six females) from 69 radiographs and plotted on normal graphs [Tanner et al., 19751. Metacarpal and phalangeal lengths were measured acC -

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Cleidocranial Dysplasia cording to the method of Garn [Garn et al., 19721. 2-scores were calculated and metacarpophalangeal pattern profiles were constructed according to the method of Poznanski [Poznanski et al., 19721, using the data of Garn et al. [1972] for comparison. The metacarpophalangeal pattern profile of each patient was compared to the mean pattern profile of the CCD patients to see if a syndrome specific pattern could be discerned. The comparison was calculated as the product moment correlation (Pearsonian r). For all quantitative data in this study, except bone maturation and metacarpophalangeal profile pattern, differences between CCD means and control means were tested with Student's

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Somatic development in cleidocranial dysplasia.

As part of a more comprehensive investigation of general and craniofacial development in cleidocranial dysplasia (CCD), the present study describes ge...
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