Multiple supernumerary teeth associated with bony malformations.

Full blown cases of cleidocranial dysplasia (CCD) have been reported earlier but a case with a rarity of 60 teeth associated with bony malformations, is seldom observed Because of the oral findings this condition has been diagnosed at an early age, thus helping to achieve a better oral harmony. This article reports an atypical case with 16 supernumerary teeth associated with bony malformations.

Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia.

UNLABELLED: Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant skeletal dysplasia characterised by hypoplastic clavicles, patent fontanelles, short stature, tooth anomalies and other variable skeletal changes. Different mutations of the RUNX2/CBFA1 gene (MIM 600211) have been detected in patients with CCD. We investigated a mother and daughter with features of CCD presenting with reduced plasma alkaline phosphatase activity, increased urinary phosphoethanolamine excretion and decreased bone density. The latter findings were suggestive of hypophophatasia but mutation analysis showed no mutation in the tissue-nonspecific alkaline phosphatase gene (TNSALP; MIM 171760). However, a heterozygous mutation (Arg169Pro caused by nucleotide change 506G > C) was detected in the RUNX2 gene. Metabolic alterations gradually improved in both mother and daughter but bone-specific alkaline phosphatase remained low (less than 30% of normal) and mild phosphoethanolaminuria persisted. Recent studies in the Cbfa1 knock-out mouse showed decreased expression of alkaline phosphatase in differentiating bone. CONCLUSION: we suggest that the observed metabolic alterations are secondary to the RUNX2 gene mutation affecting early bone maturation and turnover. This is the first description of biochemical findings of hypophosphatasia in patients with cleidocranial dysplasia.

Severe cleidocranial dysplasia can mimic hypophosphatasia.

UNLABELLED: Cleidocranial dysplasia (OMIM 119600) is a skeletal dysplasia caused by mutations in the bone/cartilage specific osteoblast transcription factor RUNX2 gene. It is characterised by macrocephaly with persistently open sutures, absent or hypoplastic clavicles, dental anomalies, and delayed ossification of the pubic bones. A few patients have been reported with recurrent fractures or osteoporosis but these are not considered features of the disease. We report a patient with classical findings of cleidocranial dysplasia: markedly hypoplastic clavicles, delayed ossification of the pubic rami, multiple pseudoepiphyses of the metacarpals, and dental anomalies including delayed eruption of permanent dentition and multiple supernumerary teeth. The patient also had radiographic and biochemical features of hypophosphatasia (OMIM 241500, 146300) and was initially diagnosed with this condition. Serum alkaline phosphatase activity has been consistently reduced and specific enzyme substrates, phosphoethanolamine and pyridoxal-5'-phosphate, have been elevated. However, no mutations were found on direct sequencing of the tissue-nonspecific alkaline phosphatase ( TNSALP) gene using a protocol that detects up to 94% of all mutations causing hypophosphatasia. CONCLUSION: We propose that a subset of patients with cleidocranial dysplasia have features of secondary hypophosphatasia due to decreased expression of the tissue-nonspecific alkaline phosphatase gene.