Clinical presentation and genetics of tricho-rhino-phalangeal syndrome (TRPS) type 1: A single-center case series of 15 patients and seven novel TRPS1 variants.

Tricho-rhino-phalangeal syndrome (TRPS) is a rare malformation syndrome characterized by distinctive facial, ectodermal, and skeletal features. TRPS is divided into TRPS type I/III caused by pathogenic variants in TRPS1 and TRPS type II caused by contiguous gene deletions also spanning EXT1 and RAD21. Due to its rarity, knowledge of the clinical course of TRPS remains limited. Therefore, we collected and characterized a case series of 15 TRPS type I patients (median age at diagnosis 15 [interquartile range: 10-18] years, 11 females [73%]) seen at Aarhus University Hospital, Denmark, with a median follow-up period of 10 years. We estimated a minimum point prevalence of 0.5 in 100,000 (95% CI: 0.3-0.8 per 100,000) persons. Common craniofacial features included fine and sparse hair with a high anterior hairline, eyebrows with lateral thinning and a thicker medial part, prominent ears, a bulbous nose tip with small nasal alae, a low-hanging, and often wide columella, and a long philtrum with a thin upper vermillion. Specific skeletal features included short stature and deviating and short fingers with cone-shaped epiphyses and shortened metacarpals on radiographs. The most significant morbidity of the cohort was joint complaints, which were reported by all patients, often already before the TRPS diagnosis was established. We identified ten different TRPS1 variants including both frameshift/nonsense, missense, and splice-site variants, including seven variants not previously reported in the literature. In accordance with previous literature, no genotype-phenotype correlation was identified. The clinical trajectories were heterogeneous involving pediatrics, dermatology, orthopedic surgery, clinical genetics, and/or odontology, emphasizing that close multidisciplinary collaboration is essential for early diagnosis of TRPS and to ensure proper and timely patient care and counseling.

Birthweight correlates to pubo-femoral distances and α angles in hip ultrasound of newborns at 6 weeks of age: a retrospective cohort study.

BACKGROUND AND PURPOSE: There is inconsistency in the literature regarding the relationship between increased birthweight and risk of developmental dysplasia of the hip (DDH). We aimed to investigate the correlation between birthweight and pubo-femoral distance (PFD), as well as Graf's α angle in newborns undergoing hip ultrasound examination at 6 weeks of age. PATIENTS AND METHODS: Basic newborn characteristics and ultrasound measurements were retrospectively collected during a 1-year study period. We excluded multiple births, newborns born at less than 37 gestational weeks, and incomplete information. Simple and multiple linear regression analyses were performed to evaluate the correlation of birthweight and PFD, and, second, birthweight and α angles including a stratified regression analysis investigating the potential effect modification of sex. RESULTS: 707 newborns (1,414 hips) were included. Mean birthweight was significantly higher for male newborns (P < 0.001). Increased birthweight was positively correlated to PFD values (crude coefficient 0.21, 95% confidence interval [CI] 0.10-0.32) and the correlation was still present after adjusting for sex, family history, and breech presentation (adjusted coefficient 0.18, CI 0.07-0.29). The stratified α angle model for the males was significant for both the crude coefficient (-0.73, CI -1.28 to -0.19) and the adjusted (-0.59, CI -1.15 to -0.03), and also for the females (crude coefficient -1.14, CI -1.98 to -0.31 and adjusted coefficient -1.15, CI -1.99 to -0.31). CONCLUSION: We found that increased birthweight positively correlated to PFD, and negatively correlated to α angle, but this was not of clinical significance.

Median nerve entrapment during closed reduction of antebrachium fracture in a child.

This is a case report of a four-year-old boy who suffered a forearm fracture managed with closed reduction and casting for six weeks. Postoperatively, the patient showed symptoms of median nerve affection which was misinterpreted as neuropraxia. Ultrasonography of the forearm revealed that the median nerve was trapped in the radius fracture site. The patient underwent a second operation with neurolysis and nerve grafting. This case report highlights the use of ultrasonography in the diagnostics of nerve entrapment neuropathy.

Controlled rotation of long bones by guided growth: A proof of concept study of a novel plate in cadavers.

Our novel plate design has been developed for controlled rotation of long bones by guided growth. The objective of this proof-of-concept study was to evaluate the precision of the rotation in the femur. Twelve cadaverous femora of six adults (right = 6, left = 6) underwent an osteotomy at the level of the physeal scar. The plates were inserted on each side of the distal femur. Growth was simulated by axial distraction of the bone segments. The femur was stabilized using a unilateral external fixator. Femoral torsion was assessed with computed tomography (CT) and with an electric goniometer before and after distraction. The obtained rotation was compared to the predicted rotation based on the dimension of the plate and the bone. All femora were rotated as intended. The mean obtained rotation was 26.3° (95% confidence interval [CI]: 23.5-29.0) and the mean predicted rotation was 28.2° (95% CI: 26.9-29.5) (p > 0.82). The mean axial distraction was 19.5 mm (95% CI: 17.7-21.3). The predicted rotation of the femora was similar to the obtained values on CT and by goniometer. The obtained rotation occurred as a result of an axial distraction of approximately 2 cm. This suggests a potential for controlled rotation of the femur based on the circumference of the bone and plate dimensions that occurs simultaneously with axial distraction. Clinical significance: These findings suggest a possible clinical application in the treatment of maltorsion in children by guided growth, where theplate design guides the bone into torsional axial growth correcting the deformity.

What is the association between MRI and conventional radiography in measuring femoral head migration?

Background and purpose - Pelvic radiographs are traditionally used for assessing femoral head migration in residual acetabular dysplasia (RAD). Knowledge of the heightened importance of cartilaginous structures in this condition has led to increased use of MRI in assessing both osseous and cartilaginous structures of the pediatric hip. Therefore, we assessed the relationship between migration percentages (MP) found on MRI and conventional radiographs. Second, we analyzed the reliability of MP in MRI and radiographs.Patients and methods - We retrospectively identified 16 patients (mean age 5 years [2-8], 14 girls), examined for RAD during a period of 2½ years. 4 raters performed blinded repeated measurements of osseous migration percentage (MP) and cartilaginous migration percentage (CMP) in MRI and radiographs. Pelvic rotation and tilt indices were measured in radiographs. Bland-Altman (B-A) plots and intraclass correlation coefficients (ICC) were calculated for agreement and reliability.Results - B-A plots for MPR and MPMRI produced a mean difference of 6.4 with limits of agreement -11 to 24, with higher disagreements at low average MP values. Mean MPR differed from mean MPMRI (17% versus 23%, p < 0.001). MPR had the best interrater reliability with an ICC of 0.92 (0.86-0.96), compared with MPMRI and CMP with ICC values of 0.61 (0.45-0.70) and 0.52 (0.26-0.69), respectively. Intrarater reliability for MPR, MPMRI and CMP all had ICC values above 0.75 and did not differ statistically significantly. Differences inMPMRI and MPR showed no correlation to pelvic rotation index, pelvic tilt index, or interval between radiograph and MRI exams.Interpretation - Pelvic radiographs underestimated MP when compared with pelvic MRI. We propose CMP as a new imaging measurement, and conclude that it has good intrarater reliability but moderate interrater reliability. Measurement of MP in radiographs and MRI had mediocre to excellent reliability.

Physical child abuse demands increased awareness during health and socioeconomic crises like COVID-19.

Background and purpose - Physical abuse of children, i.e., nonaccidental injury (NAI) including abusive head trauma (AHT) is experienced by up to 20% of children; however, only 0.1% are diagnosed. Healthcare professionals issue less than 20% of all reports suspecting NAI to the responsible authorities. Insufficient knowledge concerning NAI may partly explain this low percentage. The risk of NAI is heightened during health and socioeconomic crises such as COVID-19 and thus demands increased awareness. This review provides an overview and educational material on NAI and its clinical presentation.Methods - We combined a literature review with expert opinions of the senior authors into an educational paper aiming to help clinicians to recognize NAI and act appropriately by referral to multidisciplinary child protection teams and local authorities.Results - Despite the increased risk of NAI during the current COVID-19 crisis, the number of reports suspecting NAI decreased by 42% during the lockdown of the Danish society. Healthcare professionals filed only 17% of all reports of suspected child abuse in 2016.Interpretation - The key to recognizing and suspecting NAI upon clinical presentation is to be aware of inconsistencies in the medical history and suspicious findings on physical and paraclinical examination. During health and socioeconomic crises the incidence of NAI is likely to peak. Recognition of NAI, adequate handling by referral to child protection teams, and reporting to local authorities are of paramount importance to prevent mortality and physical and mental morbidity.

Phenotypic presentations of Hajdu-Cheney syndrome according to age - 5 distinct clinical presentations.

We present five Danish individuals with Hajdu-Cheney syndrome (HJCYS) (OMIM #102500), a rare multisystem skeletal disorder with distinctive facies, generalised osteoporosis and progressive focal bone destruction. In four cases positive genetic screening of exon 34 of NOTCH2 supported the clinical diagnosis; in one of these cases, mosaicism was demonstrated, which, to our knowledge, has not previously been reported. In one case no genetic testing was performed since the phenotype was definite, and the diagnosis in the mother was genetically confirmed. The age of the patients differs widely from ten to 57 years, allowing a natural history description of the phenotype associated with this ultra-rare condition. The evolution of the condition is most apparent in the incremental bone loss leading to osteoporosis and the acro-osteolysis, both of which contribute significantly to disease burden.

A prospective study of high resolution ultrasound in brachial plexopathies - Correlation with electrophysiological measurements.

OBJECTIVES: To evaluate the diagnostic role of ultrasound in brachial plexopathies. METHODS: We included 59 healthy subjects (HS) and 42 patients consecutively referred with clinical suspicion of brachial plexopathy from October 2015 to May 2016. Patients underwent routine electrodiagnostic testing (EDx) as reference standard and a blinded standardised ultrasound examination of the brachial plexus as index test with cross-sectional area (CSA) as the ultrasound parameter of choice. RESULTS: Seventeen patients were diagnosed by EDx with brachial plexopathy, ten with mononeuropathies, and ten had normal EDx. Five had a cervical radiculopathy. In 11 (64%) out of the 17 patients with EDx diagnosed plexopathy, we found at least one abnormal level on ultrasound. Six (60%) out of ten normal EDx patients had a normal ultrasound examination at all levels. Ultrasound identified the same abnormal level(s) as EDx in eight (73%) of the 11 patients who had both abnormal EDx and ultrasound results. Mean CSA was higher in the plexopathy group compared to HS at the level of the C6 root (p = .022), the middle trunk (p = .027), and the medial cord (p = .003). CONCLUSION: Ultrasound examination showed abnormalities in patients with brachial plexopathies in good agreement with EDx. SIGNIFICANCE: Ultrasound may be an important supplement to electrodiagnostics in evaluating brachial plexopathies.

Neuromuscular electrical stimulation in early rehabilitation of Guillain-Barré syndrome: A pilot study.

INTRODUCTION: In Guillain-Barré syndrome (GBS), patients often develop muscle atrophy from denervation and immobilization. We, therefore, conducted a pilot study of neuromuscular electrical stimulation (NMES) to evaluate feasibility, safety, and effect on muscle wasting in the early phase of GBS. METHODS: Seventeen patients were randomized to receive 20 min of muscle fiber stimulation followed by 40 min of NMES of the right or left quadriceps muscle with the untreated side as control. Cross-sectional area (CSA) of the muscle measured by ultrasound and isometric knee extensor strength were the primary and secondary outcome measures. RESULTS: No treatment related adverse effects were recorded. Change in CSA was -0.25 cm2 (confidence interval [CI], -0.93-0.42) on the stimulated side versus -0.60 cm2 (CI, -1.32-0.11) on the nonstimulated side (P = 0.08). No effect was observed on muscle strength. CONCLUSIONS: NMES seems safe and feasible in the early phase of GBS. Further studies are needed to explore effect on muscle function. Muscle Nerve 59:481-484, 2019.

Correlation of radiological and clinical measurement of genu valgum in children.

INTRODUCTION: Genu valgus is a condition characterised by a lateral shift of the knee's mechanical axis. The deformity can be characterised using clinical examinations and long hip-knee-ankle (HKA) angles, but it is unclear how these investigations correlate with each other. Our aim was to examine the correlation between clinical and radiographic measurements of the lower extremities in children. METHODS: A total of 49 children between 5.9 and 16.7 years of age who had been referred with genu valgum deformity were included. They all had their intermalleolar (IM) distance measured and a standardised anterior-posterior radiograph of the lower extremities taken. IM distance was adjusted for the mean tibial and femoral length to adjust for differences in leg length. We calculated the Spearman's rank correlation coefficient to study the reliability between radiographs and clinical examinations. RESULTS: We found no correlation between clinical IM distance and the HKA angles. Spearman's rho for comparison between adjusted clinical IM distance measurements and HKA angles on radiographs was found to be 0.36. CONCLUSIONS: We found a poor correlation between clinical examinations and HKA angles as data were corrected for leg length. More studies are needed to provide clear recommendations for following children with malalignment. FUNDING: none. TRIAL REGISTRATION: The study was registered with the Danish Data Protection Agency.

Hemiepiphysiodesis: similar treatment time for tension-band plating and for stapling: a randomized clinical trial on guided growth for idiopathic genu valgum.

BACKGROUND: In children with angulating deformities of the lower limbs, hemiepiphysiodesis can be used to guide growth to achieve better alignment at skeletal maturity. Traditionally, this has been performed with staples. The tension-band plating technique is new and it has been advocated because it is believed to reduce the risk of premature closure of the growth plate compared to stapling. The benefit of the tension-band plating technique has not yet been proven in experimental or randomized clinical studies. METHODS: We performed a randomized clinical trial in which 26 children with idiopathic genu valgum were allocated to stapling or tension-band plating hemiepiphysiodesis. Time to correction of the deformity was recorded and changes in angles on long standing radiographs were measured. Pain score using visual analog scale (VAS) was recorded for the first 72 h postoperatively. Analgesics taken were recorded by the parents. RESULTS: Mean treatment times for stapling hemiepiphysiodesis (n = 10) and for tension-band plating hemiepiphysiodesis (n = 10) were similar. Postoperative VAS scores and consumption of analgesics were also similar in both groups. No hardware failure or wound-related infection was observed. INTERPRETATION: Treatment time for the 2 treatment modalities was not significantly different in this randomized clinical trial. Tension-band plating and stapling appeared to have a similar effect regarding correction of genu valgum. We cannot rule out type-II error and the possibility that our study was underpowered. ClinicalTrials.gov Identifier: NCT01641354.

Erythropoietin augments bone formation in a rabbit posterolateral spinal fusion model.

We tested the hypothesis that erythropoietin (EPO) enhances bone formation after posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0 g autograft per side. The animals were randomly divided into two groups receiving subcutaneous daily injections of either EPO or saline for 20 days. Treatment commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4, and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively, manual palpation, radiographic, and histomorphometric examinations were performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97-3.55) in the control group (p<0.01). EPO treatment improved vascularization of the fusion mass and increased hemoglobin levels (p<0.01). Fusion rate tended to be higher in the EPO group based on manual palpation, CT, and radiographic examinations. For the first time EPO has shown to augment bone formation after autograft PLF in a rabbit model. Increased vascularization provides a partial explanation for the efficacy of EPO as a bone autograft enhancer.