Artificial intelligence-based automatic assessment of lower limb torsion on MRI.

Abnormal torsion of the lower limbs may adversely affect joint health. This study developed and validated a deep learning-based method for automatic measurement of femoral and tibial torsion on MRI. Axial T2-weighted sequences acquired of the hips, knees, and ankles of 93 patients (mean age, 13 ± 5 years; 52 males) were included and allocated to training (n = 60), validation (n = 9), and test sets (n = 24). A U-net convolutional neural network was trained to segment both femur and tibia, identify osseous anatomic landmarks, define pertinent reference lines, and quantify femoral and tibial torsion. Manual measurements by two radiologists provided the reference standard. Inter-reader comparisons were performed using repeated-measures ANOVA, Pearson's r, and the intraclass correlation coefficient (ICC). Mean Sørensen-Dice coefficients for segmentation accuracy ranged between 0.89 and 0.93 and erroneous segmentations were scarce. Ranges of torsion as measured by both readers and the algorithm on the same axial image were 15.8°-18.0° (femur) and 33.9°-35.2° (tibia). Correlation coefficients (ranges, .968 ≤ r ≤ .984 [femur]; .867 ≤ r ≤ .904 [tibia]) and ICCs (ranges, .963 ≤ ICC ≤ .974 [femur]; .867 ≤ ICC ≤ .894 [tibia]) indicated excellent inter-reader agreement. Algorithm-based analysis was faster than manual analysis (7 vs 207 vs 230 s, p < .001). In conclusion, fully automatic measurement of torsional alignment is accurate, reliable, and sufficiently fast for clinical workflows.

Position effects at the FGF8 locus are associated with femoral hypoplasia.

Copy-number variations (CNVs) are a common cause of congenital limb malformations and are interpreted primarily on the basis of their effect on gene dosage. However, recent studies show that CNVs also influence the 3D genome chromatin organization. The functional interpretation of whether a phenotype is the result of gene dosage or a regulatory position effect remains challenging. Here, we report on two unrelated families with individuals affected by bilateral hypoplasia of the femoral bones, both harboring de novo duplications on chromosome 10q24.32. The ∼0.5 Mb duplications include FGF8, a key regulator of limb development and several limb enhancer elements. To functionally characterize these variants, we analyzed the local chromatin architecture in the affected individuals' cells and re-engineered the duplications in mice by using CRISPR-Cas9 genome editing. We found that the duplications were associated with ectopic chromatin contacts and increased FGF8 expression. Transgenic mice carrying the heterozygous tandem duplication including Fgf8 exhibited proximal shortening of the limbs, resembling the human phenotype. To evaluate whether the phenotype was a result of gene dosage, we generated another transgenic mice line, carrying the duplication on one allele and a concurrent Fgf8 deletion on the other allele, as a control. Surprisingly, the same malformations were observed. Capture Hi-C experiments revealed ectopic interaction with the duplicated region and Fgf8, indicating a position effect. In summary, we show that duplications at the FGF8 locus are associated with femoral hypoplasia and that the phenotype is most likely the result of position effects altering FGF8 expression rather than gene dosage effects.

Neglected intrauterine bilateral congenital knee dislocation.

Bilateral congenital knee dislocation is a rare deformity which may present with other musculoskeletal abnormalities. In the early period, conservative treatment options have a high chance of success. However, in later stages, surgical treatment is indicated in neglected or unresponsive cases to manipulation in the early period. Herein, we present a rare case of bilateral congenital knee dislocation which was diagnosed after birth. Retrospective examination revealed that it occurred in the antenatal period and neglected.

The clinical-phenotype continuum in DYNC1H1-related disorders-genomic profiling and proposal for a novel classification.

Mutations in the cytoplasmic dynein 1 heavy chain gene (DYNC1H1) have been identified in rare neuromuscular (NMD) and neurodevelopmental (NDD) disorders such as spinal muscular atrophy with lower extremity dominance (SMALED) and autosomal dominant mental retardation syndrome 13 (MRD13). Phenotypes and genotypes of ten pediatric patients with pathogenic DYNC1H1 variants were analyzed in a multi-center study. Data mining of large-scale genomic variant databases was used to investigate domain-specific vulnerability and conservation of DYNC1H1. We identified ten patients with nine novel mutations in the DYNC1H1 gene. These patients exhibit a broad spectrum of clinical findings, suggesting an overlapping disease manifestation with intermixed phenotypes ranging from neuropathy (peripheral nervous system, PNS) to severe intellectual disability (central nervous system, CNS). Genomic profiling of healthy and patient variant datasets underlines the domain-specific effects of genetic variation in DYNC1H1, specifically on toleration towards missense variants in the linker domain. A retrospective analysis of all published mutations revealed domain-specific genotype-phenotype correlations, i.e., mutations in the dimerization domain with reductions in lower limb strength in DYNC1H1-NMD and motor domain with cerebral malformations in DYNC1H1-NDD. We highlight that the current classification into distinct disease entities does not sufficiently reflect the clinical disease manifestation that clinicians face in the diagnostic work-up of DYNC1H1-related disorders. We propose a novel clinical classification for DYNC1H1-related disorders encompassing a spectrum from DYNC1H1-NMD with an exclusive PNS phenotype to DYNC1H1-NDD with concomitant CNS involvement.

Deformity progression in congenital posteromedial bowing of the tibia: a report of 44 cases.

BACKGROUND: congenital posteromedial bowing of tibia (CPMBT) is a very rare birth defect, characterized by shortened bowed leg and ankle deformity. We described a single institution experience in the management of CPMBT. METHODS: we identified 44 CPMBT in 44 children. The age at presentation was 5.5 ± 5.6 years and the mean age at the final review was 10.1 ± 4.8 years. Radiographic evaluation included the antero-posterior and lateral inter-physeal angle (AP-IPA and L-IPA), the limb length discrepancy (LLD), the morphology of the distal tibia and the lateral distal tibial angle (LDTA). During the study period, 26 children underwent surgical treatment. RESULTS: the estimated curves showed a progressive spontaneous correction of both AP-IPA and L-IPA during growth, but a progressive increase of the LLD. The L-IPA showed a more predictable behaviour while the AP-IPA showed a scattered correction, with a wider variation of the estimated final angle. The final LDTA was 85.3° ± 4.2° and was correlated with the L-IPA (r = 0.5; p = 0.02). Among the 26 children who underwent surgical treatment, 23 cases had limb lengthening, 1 case had contralateral epiphysiodesis, 1 child underwent tibial osteotomy, 1 patient was treated by hemiepiphysiodesis of the distal tibia to correct ankle valgus deformity. CONCLUSIONS: our study described the largest case series of CPMBT. A combination of surgical treatments, in a staged surgical process, should be tailored to the developmental characteristics of this abnormality. An experience-based algorithm of treatment is also proposed. Further studies are needed to understand which is the best strategy to correct this deformity during childhood. LEVEL OF EVIDENCE: level IV prognostic study.

Familial dilated cardiomyopathy associated with pathogenic TBX5 variants: Expanding the cardiac phenotype associated with Holt-Oram syndrome.

Holt-Oram syndrome (HOS) is a rare, autosomal dominant disorder caused by heterozygous pathogenic variants in cardiac T-box transcription factor, TBX5. Classically, it is associated with upper limb malformations and variable cardiac abnormalities. Limb manifestations are considered to be invariably present, ranging in severity from limitation in movement, to triphalangeal thumbs, absent thumbs, shortened forearms, or phocomelia. Cardiac involvement is characterized by congenital heart defects, most commonly septal structural malformations, and conduction system disease. Recently, novel TBX5 variants have also been reported in association with dilated cardiomyopathy (DCM). In this context, we report eight individuals from four unrelated families, in whom pathogenic variants in TBX5 segregated with an atypical HOS phenotype. Affected individuals exhibit relatively mild skeletal features of HOS, with a predominant cardiac phenotype, which includes several individuals affected by non-ischaemic DCM. To our knowledge, these represent the first reported cases of DCM in families with skeletal features of HOS, some of whom also harbored variants previously linked to a classical HOS phenotype (p. Arg279* and p.Arg237Gln). This finding supports diverse roles of TBX5 in cardiovascular development and function, and confirms the importance of long-term cardiac surveillance for individuals affected by HOS. Furthermore, these families highlight the wide phenotypic variability of HOS, which may include comparatively mild upper limb findings in respect to cardiac manifestations.

Proximal femoral focal deficiency - a rare congenital entity: two case reports and a review of the literature.

BACKGROUND: Proximal femoral focal deficiency is an extremely rare congenital anomaly with an incidence of 1.1-2.0 in 100,000 live births. It is a dysplastic phenomenon with predilections for the proximal two-thirds of the femur leading to limb length discrepancies. We report two cases of proximal femoral focal deficiency, which is a rare entity. CASE PRESENTATIONS: Case 1 A 4.5-month-old baby Annang tribe girl was referred in April 2019 to our Radiology Department, University of Uyo Teaching Hospital, Nigeria for lower limb radiographs. This was on account of her shortened left lower limb from birth despite uneventful antenatal history. An examination revealed bulky left thigh with abduction of her left hip joint. Radiographic evaluations showed absent left femoral capital epiphysis, with deficient proximal left femur. A diagnosis of proximal femoral focal deficiency was made. Sadly, the parents and baby failed to honor future orthopedic consultations on intimation of sequential management protocols. Case 2 A 4-month-old baby Ibibio tribe girl was similarly referred in August 2019 to the same Radiology Department for lower limb conventional radiographs due to short left lower limb that was noticed from birth. An examination showed shortened left lower limb in external rotation. Her right and left lower limbs measured 27 cm and 23 cm, respectively, with landmark taken from anterior superior iliac spine to tip of medial malleolus. A diagnosis of proximal femoral focal deficiency was made. Corroborating radiographs showed shortened and hypoplastic left femoral shaft but preserved femoral capital epiphysis. Coincidentally, the parents have not brought back their baby to our orthopedic clinic. CONCLUSIONS: The discovery of two cases of proximal femoral focal deficiency, a rare entity, from referrals for conventional radiography in our Radiology Department encourages literature documentation. Such recognition will facilitate early institution of management, thus ensuring meaningful childhood growth.

First-trimester sonographic diagnosis of sirenomelia: A multicenter series of 12 cases and review of the literature.

OBJECTIVE: To determine the key sonographic features for the diagnosis of sirenomelia in the first trimester of pregnancy. METHODS: Cases of sirenomelia from several prenatal diagnosis centers were retrospectively identified and reviewed. The diagnosis was established through the detection of fused lower limbs. Additional sonographic findings were also noted. RESULTS: A total of 12 cases were collected. The most striking sonographic finding was the detection of malformed lower limbs, which appeared to be fused and in an atypical position. Nuchal translucency thickness was mildly increased in three cases (25%). An abdominal cyst, representing the dilated blind-ending bowel, was noted in seven cases (58%). Color flow imaging detected a single umbilical artery in six cases (50%) and the associated intra-abdominal vascular anomalies in three cases (25%). No cases of aneuploidy were detected. The pregnancy was terminated in nine cases (75%) and intrauterine demise occurred in the remaining three cases (25%). CONCLUSIONS: The sonographic detection of abnormal lower limbs or an intra-abdominal cyst located laterally during the first-trimester scan may be warning signs of sirenomelia. This should prompt a detailed examination of the fetal lower body and intra-abdominal anatomy, including the main abdominal vessels, in order to look for additional confirmatory findings.

Isolated unilateral proximal focal femoral deficiency presenting in a young woman.

Proximal focal femoral deficiency (PFFD) is a rare congenital skeletal abnormality characterised by the partial absence of the proximal femoral segment with shortening of the entire lower extremity. It typically presents as a shortened thigh, which is flexed, externally rotated and abducted. Some other skeletal anomalies, especially fibular hemimelia, usually accompany the disorder. The diagnosis of PFFD is made in early childhood and based mainly on conventional radiography. However, the radiographic appearance of the disease evolves as the child grows. In addition, treatment procedures applied to the child affect the radiographic presentation of the disease in adulthood. Almost all cases of PFFD reported to date are in young children and in the current literature, there is a paucity of radiographic images of PFFD in mature skeleton. The aim of this case report is to present the radiographic appearance of PFFD in an adult patient and to increase awareness among radiologists about this disease.

Precise Resection of Macrodactyly Under Assistance of Three-Dimensional Reconstruction Technology: A Case Report.

Macrodactyly of the foot is an extremely rare congenital malformation characterized by an increase in the size of all the elements or structures of a digit or digits. Most sources indicate that macrodactyly affects the hand more often than the foot. This rare medical condition usually requires surgical intervention with a precise preoperative plan and postoperative rehabilitation. We present a case of macrodactyly of the right foot in which surgical reduction of the foot under assistance of 3-dimensional image technology was performed with satisfying cosmetic and functional outcomes.

Congenital fibular dystrophisms conform to embryonic arterial dysgenesis.

The congenital short limb (CSL) with fibular deficiency has traditionally been graded by plain radiography. The most popular orthopedic classification sorts the fibular dysmorphologies into three radiographic groupings: IA (thinned), IB (proximally truncated), or II (absent). In contrast, the soft tissues have been relatively neglected. Since bone formation of the fibula progresses from the anlage, a scaffolding cartilage mold intermediate, cartilage transformation to bone is dependent upon timely embryonic arterial invasion. Absences of the requisite arteries predicate specific skeletal dysmorphologies. The usual arterial supply of the fibula is comprised primarily of the anterior tibialis artery (ATA), which uniquely supplies the proximal portion of the fibula, and also joins the peroneal artery (PA) in supplying the mid to distal fibular shaft. Combinations of the two nutrient arteries allow four potential variations of fibular vascular supply, among which the ATA and PA conjoin to supply the normal fibula and variably supply the three dysmorphic fibular models. The IA and IB deformities conform, respectively, to the absences of the PA and the ATA. Combined ATA and PA absences present in the radiographically "absent" fibula. Thus, each of the four fibular (dys)morphologies conforms to a specific embryonic pattern of arterial development. The term "dystrophism" most accurately characterizes such malformed long bones.

Myelomeningocele sac associated with worse lower-extremity neurological sequelae: evidence for prenatal neural stretch injury?

OBJECTIVE: To determine whether the presence of a myelomeningocele (MMC) sac and sac size correlate with compromised lower-extremity function in fetuses with open spinal dysraphism. METHODS: A radiology database search was performed to identify cases of MMC and myeloschisis (MS) diagnosed prenatally in a single center from 2013 to 2017. All cases were evaluated between 18 and 25 weeks. Ultrasound reports were reviewed for talipes and impaired lower-extremity motion. In MMC cases, sac volume was calculated from ultrasound measurements. Magnetic resonance imaging reports were reviewed for hindbrain herniation. The association of presence of a MMC sac and sac size with talipes and impaired lower-extremity motion was assessed. Post-hoc analysis of data from the multicenter Management of Myelomeningocele Study (MOMS) randomized controlled trial was performed to confirm the study findings. RESULTS: In total, 283 MMC and 121 MS cases were identified. MMC was associated with a lower incidence of hindbrain herniation than was MS (80.9% vs 100%; P < 0.001). Compared with MS cases, MMC cases with hindbrain herniation had a higher rate of talipes (28.4% vs 16.5%, P = 0.02) and of talipes or lower-extremity impairment (34.9% vs 19.0%, P = 0.002). Although there was a higher rate of impaired lower-extremity motion alone in MMC cases with hindbrain herniation than in MS cases, the difference was not statistically significant (6.6% vs 2.5%; P = 0.13). Among MMC cases with hindbrain herniation, mean sac volume was higher in those associated with talipes compared with those without talipes (4.7 ± 4.2 vs 3.0 ± 2.6 mL; P = 0.002). Review of the MOMS data demonstrated similar findings; cases with a sac on baseline imaging had a higher incidence of talipes than did those without a sac (28.2% vs 7.5%; P = 0.007). CONCLUSIONS: In fetuses with open spinal dysraphism, the presence of a MMC sac was associated with fetal talipes, and this effect was correlated with sac size. The presence of a larger sac in fetuses with open spinal dysraphism may result in additional injury through mechanical stretching of the nerves, suggesting another acquired mechanism of injury to the exposed spinal tissue. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Comparison between the induced membrane technique and distraction osteogenesis in treating segmental bone defects: An experimental study in a rat model.

Previous studies have suggested that treatment plans for segmental bone defects (SBDs) are affected by the bone defect sizes. If the selected treatment was not the most appropriate, it would not contribute to bone healing, but increase complications. The induced membrane technique (IM) and distraction osteogenesis (DO) have been proved to be effective in treating SBDs. However, the differences between the two in therapeutic effects on SBDs with different sizes are still unclear. Thus, we aimed to observe the effects of IM and DO on different sizes of SBDs and to further determine what method is more appropriate for what defect size. Rat models of 4-, 6-and 8-mm mid-diaphyseal defects using IM and DO techniques were established. X-rays, micro-CT, histological and immunohistochemical examinations were performed to assess bone repair. Faster bone formation rate, shorter treatment duration, higher expressions of OPN and OCN and higher parameters of bone properties including bone mineral density (BMD), bone volume/total tissue volume (BV/TV), mineral apposition rate (MAR) and mineral surface/bone surface (MS/BS) were found in 4-mm SBDs treated with DO than in those with IM treatment. However, the results were reversed and IM outperformed DO in bone repair capacity for 8-mm SBDs, while no significant difference emerges in the case of 6-mm SBDs. This study suggests that the therapeutic effects of IM and DO may be subjected to sizes of bone defects and the best treatment size of defects is different between the two. For small-sized SBDs, DO may be more suitable and efficient than IM, but IM has advantages over DO for over-sized SBDs, while DO and IM show similar bone repair capability in moderate-sized SBDs, which would offer a new insight into how to choose DO and IM for SBDs in clinical practice and provide references for further clinical research.

The risks following the exposure to radiation associated with the surgical correction of limb deformities in children are minimal.

AIMS: The aim of this study was to quantify the risk of developing cancer from the exposure to radiation associated with surgery to correct limb deformities in children. PATIENTS AND METHODS: A total of 35 children were studied. There were 19 girls and 16 boys. Their mean age was 11.9 years (2 to 18) at the time of surgery. Details of the radiological examinations were recorded during gradual correction using a Taylor Spatial Frame. The dose area product for each radiograph was obtained from the Computerised Radiology Information System database. The effective dose in millisieverts (mSv) was calculated using conversion coefficients for the anatomical area. The lifetime risk of developing cancer was calculated using government-approved Health Protection Agency reports, accounting for the age and gender of the child. RESULTS: Correction was undertaken in five femurs, 18 tibiae, and 12 feet. The median duration of treatment was 45 months (11 to 118). The mean effective dose was 0.31 mSv (0.05 to 0.64) for the femur, 0.29 mSv (0.01 to 0.97) for the tibia, and 0.027 mSv (0.001 to 0.161) for the foot. The cumulative exposure gave 'negligible' risk in 26 children and 'minimal' risk in nine children, according to Public Health England categories. These results are below the mean annual background radiation in the United Kingdom. CONCLUSION: The lifetime attributable risk of developing cancer from repeated exposure to radiation was negligible or minimal in all children. This is the first study to quantify the exposure to radiation from serial radiographs in children with limb deformities who are treated surgically using circular external fixation, linking this to the risk of developing cancer. Cite this article: Bone Joint J 2019;101-B:241-245.

Standardization of torsional CT measurements of the lower limbs with threshold values for corrective osteotomy.

INTRODUCTION: Re-establishing anatomic rotational alignment of shaft fractures of the lower extremities remains challenging. Clinical evaluation in combination with radiological measurements is important in pre- and post-surgical assessment. Based on computed tomography (CT), a range of reference values for femoral torsion (FT) and tibial torsion (TT) have historically been reported, which require standardization to optimize the significant intra- and inter-observer variability. The aims of this study were (re-)evaluation of the reference FT and TT angles, determination of the normal intra-individual side-to-side torsional differences to aid the surgical decision-making process for reoperation, and development of a novel 3D measurement method for FT. MATERIALS AND METHODS: In this retrospective study, we included 55 patients, without any known torsional deformities of the lower extremities. Two radiologists, independently, measured the rotational profile of the femora using the Hernandez and Weiner CT methods for FT, and the tibiae using the bimalleolar method for TT. The intra-individual side-to-side difference in paired femora and paired tibiae was determined. A 3D technique for FT assessment using InSpace® was designed. RESULTS: FT and TT demographic values were lower than previously reported, with mean FT values of 5.1°-8.8° and mean TT values of 25.5°-27.7°. Maximal side-to-side differences were 12°-13° for FT and 12° for TT. The Weiner method for FT was less variable than the Hernandez method. The new 3D method was equivocal to the conventional CT measurements. CONCLUSION: The results from this study showed that the maximal side-to-side tolerance in asymptomatic normal adult lower extremities is 12°-13° for FT and 12° for TT, which could be a useful threshold for surgeons as indication for revision surgery (e.g., derotational osteotomy). We developed a new 3D CT method for FT measurement which is similar to 2D and could be used in the future for virtual 3D planning.

Coronal plane alignment of the lower limbs in patients with unilateral developmental hip dislocation.

PURPOSE: We aimed to identify the coronal plane alignment of lower limbs in patients with unilateral developmental hip dislocation (UDHD) and observe the difference between Hartofilakidis type II and III. PATIENTS AND METHODS: The radiographic data of 76 patients who met the inclusion criteria were retrospectively reviewed, including the hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), anatomical lateral distal femoral angle (aLDFA), mechanical proximal tibial angle (MPTA), and lateral distal tibial angle (LDTA). RESULTS: The valgus alignment on ipsilateral side was most frequently seen in both Hartofilakidis type II (51.3%) and type III groups (67.6%), whereas for the contralateral side, the neutral alignment in type II group (69.2%) and varus alignment in type III group (51.4%) were most commonly observed. Both the mLDFA and aLDFA of the ipsilateral side were significantly smaller than the contralateral side. CONCLUSIONS: UDHD patients may present with lower limb malalignment on both sides. The ipsilateral valgus alignment is the most common deformity. On the contralateral side, Hartofilakidis type III patients may be more prone to be varus than type II patients. The lower limb malalignment and deformity of the ipsilateral distal femur should be considered during surgery involving hip, knee, or femur.