Acrodysostosis and pseudohypoparathyroidism (PHP): adaptation of Japanese patients with a newly proposed classification and expanding the phenotypic spectrum of variants

Abstract

Objective: To report on 15 Japanese patients with acrodysostosis and PHP and analyze them using the newly proposed classification of the EuroPHP network to determine whether this classification system is suitable for Japanese patients. Design: We divided them into three groups based on hormone resistance, the number of fingers with short metacarpals, the existence of cone-shaped epiphyses and gene defects. Methods: We carried out clinical, radiological and genetic evaluations of two patients in Group A (iPPSD5), 6 patients in Group B (iPPDS4) and 7 patients in Group C (iPPSD2). Results: Group A consisted of two siblings without hormone resistance who had the most severe bone and physical developmental delays. PDE4D gene defects were detected in both cases. Group B consisted of 6 patients who showed hormone resistance without hypocalcemia. Short metacarpal bones with corn-shaped epiphyses were observed in all patients. In two cases PRKAR1A gene defects were detected; however, their clinical and radiological features were not identical. The facial dysmorphism was less severe and PRKAR1A gene defects were detected in case B-3. Severe facial dysmorphism and deformity of metacarpal bones were observed but no gene defect was detected in case B-1. Group C consisted of 7 patients with PHP1a, 4 of whom had maternally inherited heterozygous inactivating mutations in one of the GNAS genes. The clinical and radiological features of the patients in Group C were not identical either. Conclusions: The newly proposed classification is suitable for Japanese patients, however; heterogeneities still existed within Groups B and C.