The molecular basis for Marfan's syndrome (MS), a heritable disorder of connective tissue, is now known to reside in mutations in FBN1, the gene for fibrillin-1. Classic phenotypic manifestations of MS include several skeletal abnormalities associated primarily with overgrowth of long bones. As a first step towards understanding how mutations in FBN1 result in skeletal abnormalities, the developmental expression of fibrillin-1 (Fib-1) in human skeletal tissues is documented using immunohistochemistry and monoclonal antibodies demonstrated here to be specific for Fib-1. At around 10–11 weeks of fetal gestation, Fib-1 is limited in tissue distribution to the loose connective tissue surrounding skeletal muscle and tendon in developing limbs. By 16 weeks, Fib-1 is widely expressed in developing limbs and digits, especially in the perichondrium, but it is apparently absent within cartilage matrix. Fib-1 appears as a loose meshwork of fibers within cartilage matrix by 20 weeks of fetal gestation. Until early ad...

Fibrillin-1 in Human Cartilage: Developmental Expression and Formation of Special Banded Fibers

Understanding the growth pattern in Marfan syndrome is important for prediction of expected growth, prevention of excessive growth by hormone therapy, timing of surgical epiphysiodesis for cessation of growth, and instituting brace treatment for scoliosis. In this study, we analyze growth patterns and generate growth charts for persons with Marfan syndrome. From the charts of 180 clinically diagnosed Marfan patients, longitudinal height and weight measurements were obtained. From this data, growth charts and growth velocity charts were generated for males and females. Skeletal maturation was studied by determining the Risser signs from the x-rays of 71 males and 56 females. From 22 female patients, age of menarche was available and retrieved either by reviewing the charts or contacting the patients. Mean length at birth was 53 ± 4.4 cm for males and 52.5 ± 3.5 cm for females. Mean final height was 191.3 ± 9 cm for males and 175.4 ± 8.2 cm for females. Mean birth weight was 3.51 ± 0.74 kg for males and 3.48 ± 0.68 kg for females. The puberty-associated peak in growth velocity was 2.4 years earlier than the gender-matched general population for males with Marfan syndrome and 2.2 years earlier for females. Age of menarche was 11.7 ± 2 years of age, which is also early compared to the general population. This study suggests that the growth spurt and pubertal skeletal maturation occur early in Marfan syndrome. The growth curves generated should help more accurately predict adult stature, as well as monitor progression toward it. © 2002 Wiley-Liss, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.10312

Growth and maturation in Marfan syndrome

We subjected the proximal tibial growth plates of six-week-old rabbits to either compression or distraction of 1 kg on both legs. On one side the proximal tibial periosteum was divided circumferentially and stripped for 1 cm. After six weeks, growth was measured at both proximal and distal growth plates. Compression inhibited total tibial growth and distraction enhanced it. The compressed growth plate grew less and the distracted growth plate grew more, but there was a reciprocal change at the other end of the bone. Periosteal division enhanced growth at the adjacent growth plate but inhibited it distally; the effect of distraction was enhanced and that of compression reduced. We found reciprocal growth rates at the proximal and distal growth plates. Relatively small amounts of compression or distraction did affect total bone growth. Periosteal division appeared to induce overgrowth at least partly by a mechanical effect; it may be useful as an adjunct to other methods of leg lengthening, though not to epiphyseolysis.

The relationship between periosteal division and compression or distraction of the growth plate

We used a rabbit model to investigate the mechanism by which the angulation of fractures is corrected in children. We produced a transverse proximal tibial fracture in one leg of 12 eight-week-old New Zealand white rabbits and measured bone alignment and length and the patterns of bone growth and remodelling. The angle between the joint surfaces changed rapidly to correct the alignment of the limb as a result of asymmetrical growth of epiphyseal plates. In an adult with closed plates, the angle between the joint surfaces cannot therefore improve. The angle at the fracture itself showed slow improvement because of bone drift and the asymmetrical growth of the epiphyseal plates. Remodelling corrected the shape of the bone in the region of the fracture. Periosteal division on the convex side increased the growth of the epiphyseal plate on that side, thus slowing the correction. The effect was relatively small, providing an indication that factors other than the periosteum are important in inducing correction. External torsional deformities developed because of helical growth at the plate. This was probably caused by abnormal posture which induced a torque at the growth plate. Helical growth is the mechanism by which rotational deformities can occur and correct.

Bone growth and remodelling after fracture

Objective—To evaluate the effect of hemi-circumferential periosteal transection and elevation (HCPTE) in foals with experimentally induced angular limb deformities. Design—Prospective study. Animals—10 healthy foals. Procedure—When foals were 30 days old, transphyseal bridge implants were placed on the lateral aspects of both distal radial physes. At 90 days of age (or when 15 degrees of angulation had developed), implants were removed, and HCPTE was performed on 1 limb. Foals were confined in small pens after surgery; the front feet of the foals were rasped weekly to maintain medial-to-lateral hoof wall balance. Dorsopalmar radiographic projections of the carpi were obtained before HCPTE and 2, 4, 6, 8, and 48 weeks later. Results—At the time of transphyseal bridge removal and HCPTE, both treated and control limbs were observed to have a significantly greater carpal valgus, compared with the initial degree of angulation at 30 days of age. Following HCPTE or sham surgery, all limbs straightened over the s...

Effect of hemi-circumferential periosteal transection and elevation in foals with experimentally induced angular limb deformities

Longitudinal growth of immature rat femurs was studied in diffusion chambers after circumferential periosteal division and stripping. After 14 days significant (P < 0.02) overgrowth of the perioste...

https://www.tandfonline.com/doi/pdf/10.3109/17453677908991285

S. Dekel

Papers

THE PERIOSTEAL CONTROL OF LONG BONE GROWTH An Experimental Study in the Rat