Case reportCleidocranial dysplasia in a mother and her two children
Introduction
Cleidocranial dysplasia (CCD, MIM 119600) is an autosomal dominant disease; and, it is characterized by clavicular hypoplasia, aplasia, dental anomalies, delayed ossification of cranial sutures and fontanelles [1]. Marie and Sainton firstly coined the name “dysostose cleido-cranienne hereditaire” for this condition in 1898 [2]. CCD is caused by haploinsufficiency of Runx2, a transcription factor that is essential for osteoblast differentiation. CCD was mapped to chromosome 6p21 proximal to the HLA region [1], [3]. The mutations identified so far include deletions of the entire gene and flanking regions, nonsense mutations and frameshifts which can be expected to result in RNA degradation, and missense mutations in the DNA binding region which were shown to interfere with DNA binding [4], [5], [6].
Here, we shall present a patient who came to us with chronic widespread pain and whose physical appearence led to the diagnosis of CCD. Her two children also had CCD. The diagnosis was confirmed in all cases by genetic analysis.
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Case 1
A 28-year-old female patient was admitted to our outpatient clinic with the complaints of widespread pain, fatigue, malaise, sleep disturbance and a nonrestorative sleep pattern. She was born from nonconsagenous parents as a healthy child and did not have any medical problem. Later, she had retarted dentition and was found to have open fontanelles. At 3 years of age, her family was told that she had rickets and that her skull bones did not form properly: she was advised to take vitamin D. She
Case 2
The 8-year-old male patient was the son of Case 1, his father did not have any medical problem. His parents were not relatives and he was born by vaginal delivery; at birth his height was at the 40th and weight was at the 50th percentile. When the physicians noticed that his fontanelles were open, his parents were told that he had vitamin D deficiency and replacement was advised. His first tooth had appeared when he was 10 months old. There was no problem in his future teeth development. He
Case 3
This 4-year-old male patient was the second son of Case 1. He was born with vaginal delivery; at birth his height was at 25th, weight at 30th and height circumference at the 90th percentile. Similar to the situation in his older brother, he was advised to take vitamin D after seeing that his fontanelles had not closed. His first tooth had appeared when he was 12 months old and he did not have further problem in teeth development. He denied the presence of any hearing problem.
On physical
Genetic analysis
In order to confirm clinical and radiological diagnoses of CCD, the genetic analyses of all patients were performed. We analyzed the entire RUNX2/CFBA1 coding sequence by PCR amplification of fragmentes of genomic DNA that span exons 1–7 and parts of the flanking intron sequences, and performed DNA sequencing of both strands. All patients were given detailed information about the aim of the study and all gave written informed consent for participation.
We identified a C–T exchange in exon 5 at
Discussion
The clinical, radiographic and molecular findings in our patient who complained of chronic widespread pain and in her two sons were in favour of CCD. The patients' parents and other relatives did not have similar findings.
The metabolic, biochemical features of subjects presented in series of CCD have not been evaluated in detail. In one of our patients (the mother), the ALP level was low in addition to the findings of CCD. Similarly, two recently published papers also reported CCD patients with
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