New Congenital Malformation Syndrome with Severe Short Stature, Craniosynostosis, and Generalized Osseous Dysplasia in Two Siblings; New Osseous Dysplasia in Two Siblings

Abstract

We present two Japanese siblings with a new congenital malformation syndrome. The patients, who are an older sister and a younger brother, were born to healthy and unrelated parents. The clinical features are characterized by proportional short stature (-5.1SD, -3.6SD), craniofacial dysmorphism related to craniosynostosis, and generalized osseous dysplasia.The skeletal changes consist of brachymesophalangy and metaphyseal dysplasia with spontaneous regression. The metaphyseal changes, which are localized in the wrists and knees, were initially cup-like radiolucencies mimicking those of rickets. The metaphyseal bony defects have been spontaneously remodeled, turning into ovoid radiolucencies and finally leaving only subtle radiolucencies at 3 or 4 years of age.GH provocation tests showed stunted response with peak serum GH of 6.7, 12.1, 1.9 ng/mL in the older sister and 7.7, 7.7, 7.9 ng/mL in the younger brother after insulin, clonidine, and I-dopa loading. The endocrinological abnormality, however, was not thought to be the cause of severe short stature in our patients.