Signaling pathways in human skeletal dysplasias.

Human skeletal dysplasias are disorders that result from errors in bone, cartilage, and joint development. A complex series of signaling pathways, including the FGF, TGFbeta, BMP, WNT, Notch, and Hedgehog pathways, are essential for proper skeletogenesis, and human skeletal dysplasias are often a consequence of primary or secondary dysregulation of these pathways. Although these pathways interact to regulate bone, cartilage, and joint formation, human genetic phenotypes point to the predominant action of specific components of these pathways. Mutations in the genes with a role in metabolic processing within the cell, the extracellular matrix, and transcriptional regulation can lead to dysregulation of cell-cell and cell-matrix signaling that alters tissue patterning, cell differentiation, proliferation, and apoptosis. We propose a morphogen rheostat model to conceptualize how mutations in different metabolic processes can lead to the integration of differential signaling inputs within a temporal and spatial context to generate apparently divergent skeletal phenotypes.

Treatment of pathological synovial plicae of the knee.

OBJECTIVE: To analyze the incidence, clinical significance, and clinical manifestations of pathological synovial plicae of the knee. MATERIAL AND METHODS: Between 2002 and 2006, 63 patients with pathological synovial plicae of the knee were studied. Of those 63 patients, 21 had the diagnosis confirmed by previously performed magnetic resonance imaging. All of the patients initially underwent conservative treatment for 90 days that involved strengthening and improving the flexibility of the muscles surrounding the knee as well as modification of their sports activities. RESULTS: A total of 55 patients improved after conservative treatment. Six of these patients eventually experienced a recurrence of symptoms, but the symptoms were not incapacitating in any of these patients. The other eight patients underwent arthroscopic removal of the synovial plica. Of these eight patients, six returned to their pretreatment physical activities, and two had persistent symptoms during physical activity. CONCLUSION: The presence of a synovial plica of the knee should be considered as a potential diagnosis in patients with knee pain, especially those who practice sports inappropriately. Conservative treatment is effective in most cases, and surgical treatment should be reserved for exceptional cases that do not improve with conservative treatment.

Treatment of pathological synovial plicae of the knee

OBJECTIVE: To analyze the incidence, clinical significance, and clinical manifestations of pathological synovial plicae of the knee. MATERIAL AND METHODS: Between 2002 and 2006, 63 patients with pathological synovial plicae of the knee were studied. Of those 63 patients, 21 had the diagnosis confirmed by previously performed magnetic resonance imaging. All of the patients initially underwent conservative treatment for 90 days that involved strengthening and improving the flexibility of the muscles surrounding the knee as well as modification of their sports activities. RESULTS: A total of 55 patients improved after conservative treatment. Six of these patients eventually experienced a recurrence of symptoms, but the symptoms were not incapacitating in any of these patients. The other eight patients underwent arthroscopic removal of the synovial plica. Of these eight patients, six returned to their pretreatment physical activities, and two had persistent symptoms during physical activity. CONCLUSION: The presence of a synovial plica of the knee should be considered as a potential diagnosis in patients with knee pain, especially those who practice sports inappropriately. Conservative treatment is effective in most cases, and surgical treatment should be reserved for exceptional cases that do not improve with conservative treatment.

Three-dimensional ultrasound diagnosis of Larsen syndrome with further characterization of neurological sequelae.

Larsen syndrome consists of skeletal dysplasia with multiple joint dislocations and a characteristic facies. The basis of this abnormality is a generalized mesenchymal disorder involving connective tissues. We describe our findings in a woman who was referred at 28 weeks' gestation due to multiple fetal anomalies suspected initially at an 18-week ultrasound examination. On three-dimensional (3D) ultrasound we found the fetus had bilateral genu recurvatum. Further 3D examination at 36 weeks confirmed the lower limb anomaly and revealed facial anomalies that led to the diagnosis of Larsen syndrome. An elective Cesarean section was performed at 38 weeks' gestation to minimize neurological sequelae. Magnetic resonance imaging was performed postnatally and showed pachygyria, colpocephaly and agenesis of the corpus callosum. In this case, 3D ultrasound facilitated the prenatal diagnosis of Larsen syndrome. A careful prenatal investigation for other associated anomalies such as those of the cardiovascular or neurological systems is warranted with this diagnosis. These associated lesions are likely to have a greater impact on prognosis than the classic symptoms of Larsen syndrome and a collaborative approach is necessary to optimize delivery and postnatal management of an affected fetus.

Morphometric study of the fetal development of the human hip joint: significance for congenital hip disease.

Hip joints (280) from 140 human fetuses, obtained from abortions and deaths in the perinatal period, were studied. The fetuses ranged from 8.7 to 40 cm in crown-rump length and are believed to be between 12 and 42 weeks in age. The joints were dissected, morphology inspected, and measurements taken of the depth and diameter of the acetabulum, the diameter of the femoral head, length and width of the ligament of the head, the neck-shaft, and torsion angles of the proximal femur. Regression models were fitted to determine which would best predict the growth pattern. Multivariate analysis of variance showed no significant differences between males and females or between the right and left sides. Acetabular depth was shown to be the slowest-growing hip variable, increasing less than fourfold in the period studied. Acetabular indices less than 50 percent indicate a shallow socket at term. Femoral head and acetabular diameter demonstrated a strong relationship (r = 0.860) and in many joints the femoral head diameter exceeded that of the acetabulum. Considerable variability was demonstrated in both femoral angles. The femoral angles showed only low correlation with the other hip variables. These observations indicate that soft tissue structures about the joint must play an important role in neonatal joint stability. The explanation of greater female and left side involvement in congenital hip disease must lie in factors other than growth changes of hip dimensions. Neither angle appears to be a useful indicator of normal joint development.