Tremor-Dominant Movement Disorder in ANKRD11- Associated KBG Syndrome.

Background: KBG syndrome is a monogenic disorder caused by heterozygous pathogenic variants in ANKRD11. A recent single-case study suggested that the clinical spectrum of KBG syndrome, classically defined by distinctive craniofacial traits and developmental delay, may include movement disorders. Case report: We report a 24-year-old patient harboring a pathogenic de novo ANKRD11 frameshift variant. The phenotype was dominated by a progressive tremor-dominant movement disorder, characterized by rest, intention and postural tremor of the hands, voice tremor, head and tongue tremor, increased muscle tone and signs of ataxia. Additionally, the patient had a history of mild developmental delay and epilepsy. Discussion: Adding to the recently described individual, our present patient highlights the relevance of movement disorders as a clinically relevant manifestation of KBG syndrome. ANKRD11 pathogenic variants should be considered in the differential diagnosis of combined tremor syndromes.

Progression of vertebral deformity of prevalent vertebral fractures in the elderly: a population-based study.

BACKGROUND: Little is known about the progression pattern of vertebral deformities in elderly patients with prevalent vertebral fractures. This population-based cohort study investigated the incidence, progression pattern, and risk factors of vertebral deformity in prevalent vertebral fractures over a finite period of four years in a population-based cohort study. METHODS: A total of 224 inhabitants of a typical mountain village underwent medical examinations every second year from 1997 to 2009, and each participant was followed up for four years. The extent (mild, moderate, severe) and type (wedge, biconcave, crush) of prevalent vertebral fractures on spinal radiographs were evaluated using the Genant semi-quantitative method. Of these participants, 116 with prevalent vertebral fractures at baseline (32 men and 84 women; mean age: 70.0 years) were included in this study. The progression patterns of the 187 vertebral fractures with mild and moderate deformities (except severe deformity) were evaluated. Logistic regression analysis was used to identify the risk factors associated with deformity progression. RESULTS: The progression of vertebral deformities was identified in 13.4% (25 vertebral fractures) of the total 187 prevalent (mild and moderate) vertebral fracture deformities over four years. Among the three deformity types, the prevalence of deformity progression was significantly lower in wedge-type vertebral fractures (P < 0.05). Age and number of prevalent vertebral fractures per participant were independent risk factors associated with the progression of prevalent vertebral deformities. CONCLUSION: This study clarified the natural history of the progression pattern of vertebral deformities in radiographic prevalent vertebral fractures in elderly individuals. Multiple vertebral fractures in the elderly present a risk for the progression of vertebral deformities.

Gradual on top-of-acute correction of neglected adolescent tibia vara by percutaneous tibial osteotomy and two-ring Ilizarov frame.

OBJECTIVES: This study aims to assess the effect of gradual correction after acute translation of the tibia in tibia vara using a two-ring Ilizarov frame on the correction of mechanical axis deviation (MAD), union time, and the rate of complications. PATIENTS AND METHODS: Between September 2018 and January 2021, a total of 30 patients (25 males, 5 females; mean age: 20±5 years; range, 15 to 25 years) with adolescent tibia vara were included. The patients had a transverse fibular ostectomy and percutaneous tibial osteotomy below the level of the tibial tuberosity. Acute correction of the rotation deformity combined with acute translation was done. A two-ring Ilizarov frame with a medial distractor and two lateral hinges were used to fix the osteotomy and the coronal plane deformity was gradually corrected. RESULTS: The mean follow-up was 24±4 months. All patients had improvement in the mechanical medial proximal tibial angle (mMPTA) and MAD postoperatively. There was an improvement in the Hospital for Special Surgery knee score at one year postoperatively. No neurovascular complications or union complications were observed. CONCLUSION: Acute translation followed by gradual angulation of the proximal tibia in cases with adolescent tibia vara yields better correction of the mechanical axis with good functional and radiological outcomes.

[Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses].

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Total Hip Replacements in Patients with Rare Pathologic Conditions Affecting Bone.

➤: As a result of the advances in surgical technique and implant design, total hip arthroplasty (THA) is increasingly offered for the management of osteoarthritis of the hip in patients with fragile or pathologic bone. ➤: Posttraumatic or congenital deformities associated with fragile or pathologic bone are frequently encountered and necessitate diligent preoperative planning. ➤: Surgeons should be prepared to evaluate and manage intraoperative iatrogenic fracture. ➤: While there is limited evidence to date, components made with computer-assisted design can be considered, given the unique and highly variable patient population.

Is cup positioning easier in DDH patients previously treated with Bernese periacetabular osteotomy?

BACKGROUND: Acetabular orientation changes after periacetabular osteotomy (PAO) lead to technical change when performing subsequent total hip arthroplasty (THA). There is no unified consensus regarding the solution for acetabular component installation after PAO. In the current study, we performed computed tomography (CT)-based simulation of acetabular component installation and compared the acetabular defect and component position following THA after PAO and the same patient before PAO. METHODS: From January 2014 to December 2018, pelvic models of 28 patients (28 hips) underwent PAO and with the risk factors to develop secondary osteoarthritis. The acetabular reconstruction process was simulated using 3D models from CT data, and the acetabular component coverage was calculated in 3D space based on the measurement and algorithm we proposed. We evaluated the anterior, posterior, superior, inferior acetabular sector angle (ASA), the medial wall thickness (MWT), and the distance from the hip center to the plane of pubic symphysis and ossa sedentarium in the study group (post-PAO group) and control group (pre-PAO group). In addition, we investigated the changes in the acetabular component covering and size between the two groups. RESULTS: A-ASA and I-ASA values were significantly smaller in the post-PAO group than in the pre-PAO group. The S-ASA and distance values were significantly bigger in the post-PAO group. Compared to the pre-PAO group, the post-PAO group has a bone defect in the anterior and inferior medial. However, the post-PAO group has to elevate the cup to improved component coverings. CONCLUSION: Acetabular defection following simulation of cup installation after PAO was significantly changed compared to those without PAO. Elevation of hip joint centers as much as 4 mm and increase acetabular cup anteversion were therapeutic options for DDH patients following THA after PAO.

[A case of cerebral infarction in young adult resulting in thrombotic occlusion of vertebral artery due to repeated contact stimulation of cervical rotation accompanied to systemic malformations such as atlantoaxial subluxation and atlas dysplasia].

A 23-year-old man admitted to our hospital with headache and dysarthria. Head MRI showed multiple acute cerebral infarctions in the right posterior circulation. Atlantoaxial dislocation, atlas dysplasia and thrombotic occlusion of right vertebral artery (VA), and blood flow disruption due to cervical rotation was observed. The axial dental process bordered to the right VA, and repeated contact stimulation by cervical rotation may cause intimal damage resulting in thrombotic occlusion. In this case, various systemic malformations such as atrial septal defect, atlas posterior arch hypoplasia, bovine left common carotid bifurcation malformation, double inferior vena cava and horseshoe kidney may have been congenital syndromes. Atlantoaxial dislocation may be an important and under-recognized cause of stroke in young adults.

Blount Disease and Obstructive Sleep Apnea: An Under-recognized Association?

BACKGROUND: Obesity is strongly associated with both Blount disease and obstructive sleep apnea (OSA). Obesity increases risks for anesthetic and postoperative complications, and OSA can further exacerbate these risks. Since children with Blount disease might have both conditions, we sought to determine the perioperative complications and the prevalence of OSA among these children. METHODS: Patients younger than 18 years undergoing corrective surgery for Blount disease were identified from 2 sources as follows: a retrospective review of records at a single institution and querying of the Kids' Inpatient Database, a nationally representative database. RESULTS: At our institution, the prevalence of OSA among patients surgically treated for Blount disease was 23% (42/184). Blount patients were obese (100%), and predominately African American (89%), and male (68%). Patients were treated for OSA before surgery, and 2 patients (1%) had postoperative hypoxemia. In contrast, of 1059 cases of Blount disease from the Kids' Inpatient Database, 3% were diagnosed with OSA. In total, 4.4% of all the Blount children experienced complications, including hypoxemia, respiratory insufficiency, atelectasis, and arrhythmias. Complications were associated with 4.3 additional days of hospitalization (P<0.0001) and 39% additional hospital charges (P=0.002). CONCLUSIONS: Data from the national database showed a low rate of OSA prevalence but high respiratory and OSA-associated complications, perhaps indicating that OSA may be underdiagnosed in children with Blount disease. Affected patients, especially ones with untreated OSA, sustain increased surgical morbidity. A high index of suspicion and preoperative planning helps alleviate the burden of OSA among these patients. LEVEL OF EVIDENCE: Level III-case-control study.

TKA in the treatment of bilateral dysplasia epiphysealis hemimelica (Trevor's Disease) of the knee in a 50-year-old man: a case report.

BACKGROUND: Dysplasia epiphysealis hemimelica (DEH), also known as Trevor's disease, is a rare skeletal developmental disorder affecting the epiphyses in pediatric patients. DEH is characterized by an asymmetric osteochondral overgrowth arising from either the medial or lateral portion of an epiphysis and usually occurs in the joints of lower limbs, most commonly in the knees and ankles. However, bilateral involvement in an adult is extremely rare, and total knee arthroplasty (TKA) for a patient with DEH has been reported only once before. CASE PRESENTATION: Here, we present a case of bilateral DEH of the knees that caused varus deformity and dysfunction of the lower limbs in a 50-year-old man. TKA was performed for treatment, and the patient had satisfactory function with no angular knee deformity and a normal range of motion after 1 year of follow-up. CONCLUSIONS: The patient in this case exhibited its specific clinical and radiological features of late-term DEH and TKA was proved to be an appropriate procedure for treating the severe deformity caused by this rare disease.

Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation.

INTRODUCTION: TBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown. METHODS: We report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network. RESULTS: 20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0-76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2-41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (D LCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma. CONCLUSION: PAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.

Hemiepiphyseodesis for Juvenile and Adolescent Tibia Vara Utilizing Percutaneous Transphyseal Screws.

BACKGROUND: In juvenile and adolescent tibia vara patients with sufficient growth remaining, implant-controlled hemiepiphyseodesis, or guided growth, can be used to correct deformity. Recent reports have described hardware failure of certain hemiepiphyseodesis implants in overweight patients with tibia vara. We describe our experience using transphyseal screws to correct deformity in this patient population. METHODS: A retrospective chart and radiograph review was conducted on all juvenile and adolescent tibia vara patients who underwent lateral proximal tibial hemiepiphyseodesis using a single transphyseal screw. Charts were queried for preoperative and postoperative mechanical axis deviation, medial proximal tibial angle, lateral distal femoral angle, and postoperative complications or need for further surgery. RESULTS: In total, 14 affected limbs in 9 patients (6 males) who underwent lateral proximal tibial transphyseal screw hemiepiphyseodesis were considered. Average chronologic age at implantation was 10.4 years and average body mass index was 31.7 kg/m. At average 23-month follow-up, the average mechanical axis deviation improved from 46 to 0 mm (P<0.001), and the average medial proximal tibial angle improved from 81 to 92 degrees (P<0.001). No limbs underwent further surgery to correct residual deformity. There were no complications or instances of implant failure associated with the transphyseal screws. CONCLUSIONS: Hemiepiphyseodesis using transphyseal screws is an effective technique to correct deformity in juvenile and adolescent tibia vara patients with sufficient growth remaining. This method can be used safely with few complications and with minimal risk of mechanical failure, even in overweight patients. LEVEL OF EVIDENCE: Level IV-therapeutic.

Results of growth-friendly management of early-onset scoliosis in children with and without skeletal dysplasias: a matched comparison.

AIMS: The aim of this study was to compare the surgical and quality-of-life outcomes of children with skeletal dysplasia to those in children with idiopathic early-onset scoliosis (EOS) undergoing growth-friendly management. PATIENTS AND METHODS: A retrospective review of two prospective multicentre EOS databases identified 33 children with skeletal dysplasia and EOS (major curve ≥ 30°) who were treated with growth-friendly instrumentation at younger than ten years of age, had a minimum two years of postoperative follow-up, and had undergone three or more lengthening procedures. From the same registries, 33 matched controls with idiopathic EOS were identified. A total of 20 children in both groups were treated with growing rods and 13 children were treated with vertical expandable prosthetic titanium rib (VEPTR) instrumentation. RESULTS: Mean preoperative major curves were 76° (34° to 115°) in the skeletal dysplasia group and 75° (51° to 113°) in the idiopathic group (p = 0.55), which were corrected at final follow-up to 49° (13° to 113°) and 46° (12° to 112°; p = 0.68), respectively. T1-S1 height increased by a mean of 36 mm (0 to 105) in the skeletal dysplasia group and 38 mm (7 to 104) in the idiopathic group at the index surgery (p = 0.40), and by 21 mm (1 to 68) and 46 mm (7 to 157), respectively, during the distraction period (p = 0.0085). The skeletal dysplasia group had significantly worse scores in the physical function, daily living, financial impact, and parent satisfaction preoperatively, as well as on financial impact and child satisfaction at final follow-up, than the idiopathic group (all p < 0.05). The domains of the 24-Item Early-Onset Scoliosis Questionnaire (EOSQ24) remained at the same level from preoperative to final follow-up in the skeletal dysplasia group (all p > 0.10). CONCLUSION: Children with skeletal dysplasia gained significantly less spinal growth during growth-friendly management of their EOS and their health-related quality of life was significantly lower both preoperatively and at final follow-up than in children with idiopathic EOS. Cite this article: Bone Joint J 2019;101-B:1563-1569.

Technical variation of trans-articular sacroiliac joint (SIJ) fusion using three screws considering the effects of sacral dysplasia in patients with non-traumatic SIJ pain.

BACKGROUND: This study evaluated the technical adequacy of trans-articular sacroiliac joint (SIJ) fusion using three screws for non-traumatic SIJ pain, considering different grades of sacral dysplasia. METHODS: Cadaveric CT data of unilateral sacropelvic complexes for 72 individuals (53.4 ± 8.4 years) were selected. A 3D model was reformatted into the plain lateral radiograph to mark the articular surface of the SIJ. Subjects were classified into dysplastic (DYS) and non-dysplastic sacrum (NDS) groups. Proximal (PS), middle (MS), and distal screws (DS) with 10-mm diameter were virtually introduced to the iliac bone and the SIJ on the lateral image with a 5-mm safety margin. On a corresponding axial image, each screw was advanced vertically to the sagittal plane with the same safety margin. The entry points for each screw to the endplate of S1 (S2) and to the corresponding anterior sacral margin on the lateral image were measured, along with the maximal screw lengths on the axial image. Whether each screw passed through the SIJ was determined. Different types of sacral dysplasia and screws were compared statistically. RESULTS: Thirty-eight (26.4%) cases were DYS, and 106 (73.6%) were NDS. The entry points of all screws were significantly more distal in DYS than in NDS groups. The PS and MS screw lengths differed significantly between the 2 groups. Incidences of short sacral fixation (< 10 mm) were significantly higher for the DS in both NDS (38.7%) and DYS (39.5%) groups. Incidences of screw pass were lowest for the MS in both NDS (43.4%) and DYS (47.4%) groups. CONCLUSIONS: Sacral dysplasia locates the SIJ more distally and therefore affects the entry point locations and screw lengths for all screws in trans-articular SIJ fusion, compared with a non-dysplastic sacrum. Moreover, three-screw fixation risks the development of unstable DS fixation and a high extra-articular fixation rate in MS.

Osteofibrous Dysplasia of the Tibia in Children: Outcome Without Resection.

BACKGROUND: The proposed association between osteofibrous dysplasia and adamantinoma has led some to advocate resection of the entire lesion, which can require major subsequent reconstruction. However, this link remains unproven and there is some support in more recent literature for a less aggressive approach. This study aims to describe our experience managing pediatric tibial osteofibrous dysplasia with such an approach and to report functional outcomes in children treated thus. METHODS: A total of 28 cases of osteofibrous dysplasia in 25 patients were managed at a referral center for pediatric bone tumors with observation in the first instance, then limited surgical intervention if required to address pain and deformity. Surgery aimed to restore stability and alignment without excising the lesion. Clinical records provided basic clinical outcome measures involving walking, recreation, orthoses and school/work participation and patients provided a Musculoskeletal Tumour Society score (MSTS) where contactable. RESULTS: Mean age at presentation was 6.0 years and mean follow-up was 8.3 years. Only 8 patients required surgery. According to basic outcome measures, 13 patients were symptom-free. About 15 patients (17 cases) provided a MSTS and the mean score was 24 of 30. No transformation to adamantinoma was observed. Those who presented at a younger age and with bilateral disease more often required surgery and remained symptomatic. CONCLUSIONS: A less aggressive approach to pediatric tibial osteofibrous dysplasia achieves good functional outcomes and patient satisfaction in most cases. Surgery is required in the minority of cases. Transformation to adamantinoma was not observed in this series. We recommend patient education, clinical observation and reactive intervention if required, rather than proactive resection and reconstruction. LEVEL OF EVIDENCE: Level IV-case series.

Combined navigated drilling and arthroscopy facilitate minimally invasive surgical treatment of ulnar-radial joint dislocation caused by epiphyseal premature closure: A case report.

RATIONALE: In this paper, the efficacy and safety of using navigated drilling and arthroscopy (NDA) to assist surgery for ulnar-radial joint dislocation caused by epiphyseal premature closure (EPC) are described. Deformity correction surgery was mentioned in the literature, but there were numerous complications, for example, poor correction, infection, neurovascular injury, osteofascial compartment syndrome, failure of internal fixation, and nonunion after osteotomy. In order to minimize surgical complications, we utilized navigated drilling to finish accuracy bone bridge resection and applied arthroscopy to assess wrist lesions. PATIENT CONCERNS: An 11-year-old male patient showed swelling and pain of the left wrist. DIAGNOSES: The patient was diagnosed with a postoperative of Kirschner wire internal fixation for epiphyseal injury, left lower ulnar-radial joint dislocation, left wrist deformity, and EPC. INTERVENTIONS: A NDA was used to assist the bone bridge resection in this patient. OUTCOMES: Pain was relieved clearly in the patient. Dorsiflexion increased from 60.8° to 85.3°, palmar flexion increased from 45.3° to 65.8°, supination increased from 41.3° to 69.5°, and pronation increased from 31.6° to 62.9°. The preoperative disabilities of the arm, shoulder, and hand (DASH) score was 86.1, which was increased to 16.4 postoperatively. Surgery designing lasted for 2 minutes, bone bridge resection lasted for 56 minutes, and fluoroscopic time was 2.4 minutes. Complications, for example, neurological injury, vascular injury, infection and deformity aggressive, were not found during the 5-month follow up. LESSONS: The outcome of the present study suggests that the NDA maximizes the bone bridge resection accuracy in EPC treatment, which is made efficient by reducing surgical trauma and avoiding neurovascular injury. An experience was gained that in the process of bone bridge removal, the bit of navigated drill should be continuously washed with normal saline to cool down, so as to avoid damage of nerve caused by heat conduction.