Skeletal maturation and long-bone growth patterns of patients with progeria: a retrospective study.

BACKGROUND

Hutchinson-Gilford progeria syndrome (termed progeria in this Article) is a rare sporadic genetic disorder. One early clinical manifestation of progeria is abnormal skeletal growth, yet this growth has not been fully characterised. We aimed to characterise the skeletal maturation and long-bone growth patterns of patients with the clinical phenotype of progeria.

METHODS

For this retrospective study, we reviewed skeletal surveys of patients (aged <20 years) with progeria obtained over a 9·5-year period. Most surveys included radiographs of the hands and long bones (humeri, radii, ulnas, tibias, and fibulas). Bone ages of these patients were estimated by the standards of Greulich and Pyle. Following the established methods for studying long-bone growth, the study cohort was separated into two overlapping age groups: longitudinal bone length measurements were made between physes for the childhood group (aged 12 years or younger) and from the upper margins of the proximal to the lower margin of the distal ossified epiphyses for the adolescent group (aged 10 years or older). Bone age estimates and bone length measurements were plotted against the chronological age of patients and compared with reference standards. Statistical analyses were based on mixed models.

FINDINGS

85 patients with progeria and 250 skeletal surveys were included in our study. For both sexes, bone age estimates showed a more advanced skeletal maturation rate throughout all chronological ages than the normal rate of 1 (p<0·0001), with the rate of maturation being 1·09 (SE 0·02) for boys and 1·14 (0·02) for girls. Longitudinal long-bone lengths began to deviate from normal standards by age 1-2 years. Growth curves for these long bones plateaued at about half the normal eventual bone length, and the half-life (the time taken to grow to half the eventual bone length) was also about half the time compared with normal standards.

INTERPRETATION

Our study established growth curves that might serve as reference standards for skeletal maturation and long-bone growth of patients with the clinical phenotype of progeria.

FUNDING

The Progeria Research Foundation, the US National Heart, Lung and Blood Institute, the Dana-Farber Cancer Institute Stop&Shop Pediatric Brain Tumor Program, the US National Center for Research Resources, US National Institutes of Health.