Severe cleidocranial dysplasia can mimic hypophosphatasia.
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.


CONCLUSIONS
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.
Unger
Sheila
S
Division of Clinical and Metabolic Genetics, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. sheila.unger@sickkids.ca
Mornet
Etienne
E
Mundlos
Stefan
S
Blaser
Susan
S
Cole
David E C
DE
D000469:Alkaline Phosphatase / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000209:etiology; D002648:Child; D002973:Cleidocranial Dysplasia / Q000150:complications* / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006801:Humans; D007014:Hypophosphatasia / Q000150:complications* / Q000235:genetics; D011859:Radiography; D012600:Scoliosis / Q000209:etiology
D000469:Alkaline Phosphatase