We examined the arthroscopic appearance of the anterior cruciate ligament (ACL) attachment site on the femur in five fresh-frozen cadaver knees. First, the ACL was cut out, leaving a footprint of ligament-fibers with a length of 2 mm intact. The ACL was consistently found to insert on the lateral wall of the notch. No fibers were found to attach high in the roof of the notch at the 12 o'clock position. Secondly, we tried to reach the anatomical attachment site with a femoral aiming guide through a correctly placed tibial tunnel. This proved to be impossible. The closest position that could be reached was at the margin of the anatomical attachment site. Investigation of the distal femur after complete dissection confirmed these arthroscopic findings. Femoral aiming devices for use through the tibial tunnel aim for an isometric placement of the femoral tunnel, they do not aim for an anatomical position of the graft.

Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype -phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.

Small patella syndrome (SPS) is an autosomal-dominant skeletal dysplasia characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami. We identified an SPS critical region of 5.6 cM on chromosome 17q22 by haplotype analysis. Putative loss-of-function mutations were found in a positional gene encoding T-box protein 4 (TBX4) in six families with SPS. TBX4 encodes a transcription factor with a strongly conserved DNA-binding T-box domain that is known to play a crucial role in lower limb development in chickens and mice. The present identification of heterozygous TBX4 mutations in SPS patients, together with the similar skeletal phenotype of animals lacking Tbx4, establish the importance of TBX4 in the developmental pathways of the lower limbs and the pelvis in humans.

A study was undertaken to provide data on the three-dimensional tracking pattern of the patella, relative to the femur, in human knee-joint specimens. For this purpose, a highly accurate roentgen stereophotogrammetric analysis (RSA) method was applied. The three-dimensional motion patterns of the tibia and the patella were measured and represented in terms of three translations and three rotations each, during knee flexion in neutral (unloaded), endorotated, and exorotated pathways. We found that the patella displays complex but consistent three-dimensional motion patterns during flexion, which include flexion rotation, medial rotation, wavering tilt, and a lateral shift relative to the femur. The motion patterns are very much affected by tibial rotations accompanying flexion.

Rotational malalignment after intramedullary nailing for femoral fractures is found in 28% of the patients in this study. These patients have difficulties with more demanding activities, especially when they have an external torsional deformity.