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Cleidocranial dysplasia (CCD) is an inherited development anomaly of the skeletal system that is also classified as an autosomal dominant genetic disorder. This is due to a gene mutation on chromosome 6p21 that encodes core binding factor activity a-1 (CBFA1), a member of runt-related transcription factor 2 (RUNX2) found on the short arm of chromosome 6. CCD is a scarce condition and its occurrence is about one per million births. It primarily affects bones that are derived from both endochondral and intramembranous ossification. It is identified by certain clinical and radiological features including open cranial sutures and open anterior fontanelle, aplastic or hypoplastic clavicles, wormian bones, short stature, deformities of the pelvic bones, and various skeletal changes. Patients usually show class III malocclusion because of mandibular hyperplasia and mid-face hypoplasia. Vertical facial growth is reduced due to hypoplasia of the alveolar bone, and permanent teeth eruptions are failed. We reported a case of CCD in a 28-year-old who was referred to OPD for poor esthetics., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gollapudi et al.)

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia. Hypoplastic clavicles, delayed closure of the cranial sutures, dental abnormalities, and short stature are main features in this syndrome. RUNX2 is the responsible gene for CCD. Here we reported two cases with CCD; they are admitted to clinic for short stature and dental abnormalities. We report these cases to increase the awareness of clinicians. [ABSTRACT FROM AUTHOR]

IntroductionCongenital anomalies of the kidney and urinary tract (CAKUT) represent the primary cause of chronic kidney disease in children. Many genes have been attributed to the genesis of this disorder. Recently, haploinsufficiency of PBX1 caused by microdeletions has been shown to result in bilateral renal hypoplasia and other organ malformations.Materials and methodsHere, we report on a 14-year-old male patient with congenital bilateral dysplastic kidneys, cryptorchidism, hypoplastic clavicles, developmental delay, impaired intelligence, and minor dysmorphic features. Presuming a syndromic origin, we performed SNP array analysis to scan for large copy number variations (CNVs) followed by whole-exome sequencing (WES). Sanger sequencing was done to confirm the variant’s de novo status.ResultsSNP array analysis did not reveal any microdeletions or -duplications larger than 50 or 100 kb, respectively. WES identified a novel heterozygous 7-bp frameshift deletion in PBX1 (c.413_419del, p.Gly138Valfs*40) resulting in a loss-of-function. The de novo status could be confirmed by Sanger sequencing.DiscussionBy WES, we identified a novel heterozygous de novo 7-bp frameshift deletion in PBX1. Our findings expand the spectrum of causative variants in PBX1-related CAKUT. In this case, WES proved to be the apt technique to detect the variant responsible for the patient’s phenotype, as single gene testing is not feasible given the multitude of genes involved in CAKUT and SNP array analysis misses rare single-nucleotide variants and small Indels.

Cleidocranial dysplasia is a disease that occurs secondary to a dominant autosomal inheritance. There is no predilection for any genre or ethnic group. As there is a delay in the eruption and/or absence of permanent teeth, the patients usually report to a dental surgeon for replacement of the missing teeth. This condition is characterized by several cranial malformations and underdevelopment, absence of clavicles, and multiple impacted supernumerary and permanent teeth. The diagnosis of the condition is usually based on the presence of the above-mentioned main features and on clinical and familial evidence. Here we report a rare case of cleidocranial dysplasia in a male patient, having most of the characteristic features of this syndrome.

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles, late closure of the fontanels, dental problems and other skeletal features. CCD is caused by mutations, deletions or duplications in runt-related transcription factor 2 ( RUNX2), which encodes for a protein essential for osteoblast differentiation and chondrocyte maturation. We describe three familial cases of CCD, misdiagnosed as rickets over three generations. No mutations were detected on standard DNA sequencing of RUNX2, but a novel deletion was identified on quantitative polymerase chain reaction (qPCR) and multiple ligation-dependent probe amplification (MLPA). The present cases indicate that CCD could be misdiagnosed as rickets, leading to inappropriate treatment, and confirm that mutations in RUNX2 are not able to be identified on standard DNA sequencing in all CCD patients, but can be identified on qPCR and MLPA. [ABSTRACT FROM AUTHOR]

Cleidocranial dysplasia is a rare autosomal dominant condition with generalized dysplasia of bone, characterized by delayed closure of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. In this case report, we describe an otherwise healthy 11 year-old male child with a chief complaint of missing anterior maxillary teeth who was diagnosed with cleidocranial dysplasia. [ABSTRACT FROM AUTHOR]