Metaphyseal Undermodeling, Spondylar Dysplasia, And Overgrowth

Nishimura et al. (2004) described 3 unrelated individuals with generalized skeletal alterations and overgrowth: a boy who died at age 16 years, a 16-year-old girl, and a 15-month-old boy. The skeletal changes included bony overgrowth of the skull base, spondylar dysplasia, and undermodeling of the tubular bones. Bone age was accelerated in early childhood. The overgrowth was independent of the growth hormone/insulin-like growth factor-1 (147440) axis and was of prenatal onset in both boys but postnatal in the girl. In the 2 adolescents, growth rate did not decline with age, and high-dose estrogen therapy failed to induce physeal fusion. Their adolescent height reached +4 to +7 SD of the mean. Delayed puberty in the girl and cryptorchidism and hypospadias in the younger boy raised the possibility that hypogonadism is a syndromic constituent. Common facial features included puffy eyelids, mild hypertelorism, depressed nasal bridge, and full lower lip. Molecular analysis of IGF2 (147470), GPC3 (300037), and FGFR3 (134934) in the older boy yielded no abnormalities.