A case of amelogenesis imperfecta, cleft lip and palate and polycystic kidney disease.

OBJECTIVE: Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders characterized by developmental abnormalities of tooth enamel. The AI is also seen as part of multi-organ abnormalities, e.g. with cone-rod dystrophy, hypothalamo-hypophyseal insufficiency and renal failure. The present patient with AI and nephrocalcinosis exhibited a phenotype different from previous cases with renal failure. To highlight the characteristics of this rare case, extensive analysis that included histological, biochemical and genetic examinations was performed. PATIENT: The present Japanese male patient exhibited dentition with AI and bilateral cleft lip and palate. Ground sections of his extracted tooth showed that it was hypomaturation-type AI, unlike previous cases with nephrocalcinosis were hypoplastic-type. He showed nephrocalcinosis and hematuria at 15 years of age but these symptoms appeared to be secondary to polycystic kidney disease. He showed skeletal Class II pattern with a retrognathic profile and retroclined incisors of both arches. A dolicofacial appearance was seen with an enlarged gonial angle. Biochemical makers including serum alkaline phosphatase, parathyroid hormone, calcitonin, calcium, and phosphate, were all in the normal range. Sequence analysis of the genes encoding amelogenin and enamelin, which are known to be responsible for hypoplastic-type AI, did not reveal any mutations. Since mouse null mutant of homeobox transcription factor, Msx2, exhibits a phenotype resembling AI, the human homolog of this gene, MSX2, was sequenced. There was a missense mutation of T447C that resulted in the conversion of methionine to threonine at 129.