Post-traumatic proximal radioulnar synostosis: results of surgical treatment and review of the literature.

BACKGROUND: Post-traumatic proximal radioulnar synostosis is a very rare and disabling condition whose surgical treatment has traditionally been viewed with pessimism. The results of the few case series in the literature are conflicting. Our aims were (1) to describe the clinical results of a case series treated surgically by a single elbow surgeon and (2) to review the literature. METHODS: Twelve patients were evaluated. Preoperative radiographs and computed tomography scans were performed. According to the Viola and Hastings classification, there was 1 case of type IC synostosis; 3, type IIA; 2, type IIIA; and 8, type IIIB. Two patients had a double synostosis. The synostosis was excised in 10 cases; in addition, radial head excision, radial head arthroplasty, and proximal radial diaphyseal resection were performed in 1, 3, and 2 cases, respectively. The Mayo Elbow Performance Score, modified American Shoulder and Elbow Surgeons score, and QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score were used for the preoperative and postoperative evaluation. The nonparametric Wilcoxon signed rank test was used for the statistical analysis. RESULTS: The mean follow-up period was 20.5 months. The final mean extension-flexion and pronation-supination arcs were 116° and 123°, respectively. Significant improvements were found in the Mayo Elbow Performance Score (P = .005), modified American Shoulder and Elbow Surgeons score (P = .012), and QuickDASH score (P = .002), with mean values of 24, 28, and 17, respectively. One synostosis recurrence and one late disassembly of the radial head arthroplasty were observed. CONCLUSIONS: Post-traumatic proximal radioulnar synostosis surgery is effective, but careful preoperative planning based on the pathoanatomic characteristics of each type of synostosis and associated lesions is mandatory. Synostosis excision is performed in most cases, whereas additional surgical procedures should be considered in selected cases.

Seven additional families with spondylocarpotarsal synostosis syndrome with novel biallelic deleterious variants in FLNB.

The location and/or type of variants in FLNB result in a spectrum of osteochondrodysplasias ranging from mild forms, like spondylocarpotarsal synostosis syndrome and Larsen syndrome, to severe perinatal lethal forms, such as atelosteogenesis I and III and Boomerang dysplasia. Spondylocarpotarsal synostosis syndrome is characterized by disproportionate short stature, vertebral anomalies and fusion of carpal and tarsal bones. Biallelic loss-of-function variants in FLNB are known to cause spondylocarpotarsal synostosis syndrome and 9 families and 9 pathogenic variants have been reported so far. We report clinical features of 10 additional patients from 7 families with spondylocarpotarsal synostosis syndrome due to 7 novel deleterious variants in FLNB, thus expanding the clinical and molecular repertoire of spondylocarpotarsal synostosis syndrome. Our report validates key clinical (fused thoracic vertebrae and carpal and tarsal coalition) and molecular (truncating variants in FLNB) characteristics of this condition.

Further delineation of the GDF6 related multiple synostoses syndrome.

A mutation in GDF6 was recently found to underlie a multiple synostoses syndrome. In this report, we describe the second family with GDF6-related multiple synostoses syndrome (SYNS4), caused by a novel c.1287C>A/p.Ser429Arg mutation in GDF6. In addition to synostoses of carpal and/or tarsal bones, at least 6 of 10 affected patients in this family have been diagnosed with mild to moderate hearing loss. In four of them otosclerosis was said to be present, one patient had hearing loss due to severe stapes fixation at the age of 6 years, providing evidence that hearing loss in the GDF6-related multiple synostoses syndrome can be present in childhood. Two others had surgery for stapes fixation at adult age. We hypothesize that, identical to the recently published GDF6-related multiple synostoses family, the p.Ser429Arg mutation also leads to a gain of function. The previously reported c.1330T>A/pTyr444Asn mutation was located in a predicted Noggin and receptor I interacting domain and the gain of function was partly due to resistance of the mutant GDF6 to the BMP-inhibitor Noggin. The results in our family show that mutations predicting to affect the type II receptor interface can lead to a similar phenotype and that otosclerosis presenting in childhood can be part of the GDF6-related multiple synostoses syndrome.

FGF9 mutation causes craniosynostosis along with multiple synostoses.

Craniosynostosis is commonly caused by mutations in fibroblast growth factor receptors (FGFRs), highlighting the essential role of FGF-mediated signaling in skeletal development. We set out to identify the molecular defect in a family referred for craniosynostosis and in whom no mutation was previously detected. Using next-generation sequencing, we identified a novel missense mutation in FGF9. Modeling based upon the crystal structure and functional studies confirmed its pathogenicity showing that it impaired homodimerization and FGFR3 binding. Only one FGF9 mutation has been previously reported in a multigeneration family with multiple synostoses (SYNS3) but no signs of craniosynostosis. In contrast, our family has a greater phenotypic resemblance to that observed in the Fgf9 spontaneous mouse mutant, elbow-knee-synostosis, Eks, with both multiple synostoses and craniosynostosis. We have demonstrated for the first time that mutations in FGF9 cause craniosynostosis in humans and confirm that FGF9 mutations cause multiple synostoses.

A 590 kb deletion caused by non-allelic homologous recombination between two LINE-1 elements in a patient with mesomelia-synostosis syndrome.

Mesomelia-synostoses syndrome (MSS) is a rare, autosomal-dominant, syndromal osteochondrodysplasia characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations due to a non-recurrent deletion at 8q13 that always encompasses two coding-genes, SULF1 and SLCO5A1. To date, five unrelated patients have been reported worldwide, and MMS was previously proposed to not be a genomic disorder associated with deletions recurring from non-allelic homologous recombination (NAHR) in at least two analyzed cases. We conducted targeted gene panel sequencing and subsequent array-based copy number analysis in an 11-year-old undiagnosed Japanese female patient with multiple congenital anomalies that included mesomelic limb shortening and detected a novel 590 Kb deletion at 8q13 encompassing the same gene set as reported previously, resulting in the diagnosis of MSS. Breakpoint sequences of the deleted region in our case demonstrated the first LINE-1s (L1s)-mediated unequal NAHR event utilizing two distant L1 elements as homology substrates in this disease, which may represent a novel causative mechanism of the 8q13 deletion, expanding the range of mechanisms involved in the chromosomal rearrangements responsible for MSS.

A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFß signaling and cause autosomal dominant spondylocarpotarsal synostosis.

Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFß signaling, revealing a regulatory role for embryonic myosin in the TGFß signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions.

[Alagille's syndrome associated with proximal radio-ulnar synostosis: Clinical case and a literature review]. / Síndrome de Alagille asociado a sinostosis radiocubital proximal: caso clínico y revisión de la literatura.

Alagille's syndrome is an infrequent genetic condition with autosomal inheritance and variable expression. The complete form exhibits 5 clinical signs, chronic intrahepatic cholestasis, characteristic facies, cardiovascular anomalies, posterior embryotoxon, and vertebral defects. If only 3 or 4 of these are present the case is considered as an incomplete form. The association of Alagille's syndrome with radio-ulnar synostosis is extremely rare. There is only one case described in the indexed literature. A case is presented of Alagille's syndrome with bilateral proximal radioulnar synostosis. To the best of our knowledge this is the second reported case of this association.

Incidence and clinical relevance of tibiofibular synostosis in fractures of the ankle which have been treated surgically.

In this retrospective cohort study, we analysed the incidence and functional outcome of a distal tibiofibular synostosis. Patients with an isolated AO type 44-B or C fracture of the ankle who underwent surgical treatment between 1995 and 2007 were invited for clinical and radiological review. The American Orthopaedic Foot and Ankle Society score, the American Academy of Orthopaedic Surgeons score and a visual analogue score for pain were used to assess outcome. A total of 274 patients were available; the mean follow-up was 9.7 years (8 to 18). The extent of any calcification or synostosis at the level of the distal interosseous membrane or syndesmosis on the contemporary radiographs was defined as: no or minor calcifications (group 1), severe calcification (group 2), or complete synostosis (group 3). A total of 222 (81%) patients were in group 1, 37 (14%) in group 2 and 15 (5%) in group 3. There was no significant difference in incidence between AO type 44-B and type 44-C fractures (p = 0.89). Severe calcification or synostosis occurred in 21 patients (19%) in whom a syndesmotic screw was used and in 31 (19%) in whom a syndesmotic screw was not used.(p = 0.70). No significant differences were found between the groups except for a greater reduction in mean dorsiflexion in group 2 (p = 0.004). This is the largest study on distal tibiofibular synostosis, and we found that a synostosis is a frequent complication of surgery for a fracture of the ankle. Although it theoretically impairs the range of movement of the ankle, it did not affect the outcome. Our findings suggest that synostosis of the distal tibiofibular syndesmosis in general does not warrant treatment.

Surgical Considerations for Massive Tarsal Coalitions in Multiple Synostosis Syndrome: A Case Report.

Tarsal-carpal coalition syndrome is an autosomal dominant inherited condition characterized by fusion of the carpal and tarsal bones and foot deformity. Associated pain and/or gait disturbance are the main complaints. The deformity usually consists of varying degrees of hindfoot varus and forefoot supination. The treatment of these patients is mainly aimed at symptomatic relief. We performed a published data review of this condition and discuss our findings in the context of the case of a 10-year-old female with congenital varus deformity of both feet. The tarsal-carpal coalition syndrome has been included in the spectrum of heritable disorders related to mutations in the NOG gene. Deformity management should be customized to the patient's requirements, and satisfactory results are achievable with adequate rehabilitation. It is important to remember that surgery is only necessary for symptomatic relief and that patients with tarsal-carpal coalition syndrome should be followed up over time because the condition can evolve.

Thoracic outlet syndrome caused by synostosis of the first and second thoracic ribs: 2 case reports and review of the literature.

We present 2 cases of combined arterial and neurogenic thoracic outlet syndrome triggered by trauma in patients with congenital synostoses of the first and second ribs. These patients were successfully treated with supraclavicular resection of the first and second ribs and scalenectomy. We review these cases and the associated literature on thoracic outlet syndrome and rib synostosis.

Treatment of naviculo-first cuneiform coalition of the foot.

BACKGROUND: Naviculo-first cuneiform coalition is a rare form of tarsal coalition with few reports. We therefore have analyzed its clinical features and the results of treatment. METHODS: We analyzed 36 feet in 28 patients diagnosed with naviculo-first cuneiform coalition from January 2003 to December 2010. The 28 patients were 10 males and 18 females, with 18 right and 18 left feet, including 8 patients with bilateral coalition. The location and morphological pattern of naviculo-first cuneiform coalition were analyzed radiologically. Symptomatic patients initially received conservative management for 6 months. Six feet of 5 patients were treated operatively, 3 feet by curettage and 3 by fusion. RESULTS: Eighteen feet had symptoms, while 18 feet without symptoms were diagnosed incidentally. Mean patient age at diagnosis was 34.6 years (range, 10-68 years). The mean age at diagnosis of symptomatic patients was 29.6 years (range, 10-50 years). Coalitions were located mainly in the medioplantar area. There was no bony coalition. Computed tomography or magnetic resonance imaging showed a cystic pattern in 7 patients, an irregular pattern in 4, a combined pattern in 5, and a spur-forming pattern in 1. The mean American Orthopaedic Foot & Ankle Society scores at the last follow-up in patients treated conservatively and operatively were 95.3 (range, 87-100) and 83.5 (range, 70-95), respectively. Among the 5 operated patients, 3 patients (60%) complained of pain, including 2 who received curettage and 1 who developed a nonunion after attempted fusion. CONCLUSION: Conservative treatment should be considered over surgery in treating naviculo-first cuneiform coalition. LEVEL OF EVIDENCE: Level III, comparative case series.

A case of Robin sequence, microgastria, radiohumeral synostosis, femoral deficiency, and other unusual findings: a newly recognized syndrome?

In this report, we describe an 8-year-old male with Robin sequence, bilateral radiohumeral synostosis, microgastria, cryptorchidism, dislocated hips, proximal femoral deficiency, and an autism spectrum disorder. This combination of findings has not been previously reported. Features of particular interest are the radiohumeral synostosis and microgastria, both of which are rare defects, and to our knowledge, have not been reported to occur together. We propose that the patient has a newly recognized syndrome consisting of the aforementioned features, the etiology of which is unknown.

Idiopathic distal radioulnar synostosis.

Radioulnar synostosis is rare, and exists in two forms: congenital and post-traumatic. The congenital form presents only in the proximal forearm, and the post-traumatic form may present anywhere along the radius and ulna. The only known aetiology for distal radioulnar synostosis is post-traumatic. We present a rare case of distal radioulnar synostosis with no previous history of trauma.

Diaphyseal tibiofibular synostosis in a runner.

Diaphyseal tibiofibular synostosis is a very rare cause of shin and ankle pain. A 35-year-old male presented with complaints of left shin and ankle pain of 3 years duration that was sometimes worse after running a few miles. One year before presenting to our hospital, the actual cause for his pain was missed when only lumbar radiographs were taken at another institution. A full-length tibia film revealed a diaphyseal tibiofibular synostosis at our hospital. The presence of a synostosis should alert the surgeon to search for the various abnormalities usually associated with this condition. Magnetic resonance imaging and enhanced 3-dimensional computed tomography are essential to rule out the possibility of a neoplastic process and to determine its relation to the neurovascular structures. Simple excision of the synostosis can provide excellent symptomatic relief with a minimal risk of complications.

[Diagnosis and treatment of tarsal coalitions and synostoses in children and adolescents]. / Diagnostik und Therapie der Koalitionen und Synostosen bei Kindern und Jugendlichen.

The majority of tarsal coalitions are located in the calcaneonavicular and talocalcaneal regions and other locations are rare. Complete early ossified synostoses are found not only in major limb deficiencies but also in otherwise normal feet. Magnetic resonance imaging (MRI) and computed tomography (CT) scans are the most important imaging techniques especially for preoperative planning. Early resection is advisable in calcaneonavicular coalitions as soon as it is detected in childhood and adolescence. Indications for or against resection or limited tarsal fusion are much more difficult in talocalcaneal coalition. The patient's complaints, extension and location of the coalition, additional malalignment and especially patient age are some of the factors that should be considered carefully. Results of surgical resection are not always satisfactory with a long-lasting rehabilitation especially in older children or adolescents and the necessity for secondary procedures can never be ruled out. In cases of malalignment corrective tarsal osteotomy can be considered as a simultaneous or staged procedure. An overview with special emphasis on surgical options is presented with typical examples as well as rare conditions and a review of important literature from recent years is included.

Inherited thrombocytopenias: an approach to diagnosis and management.

Inherited thrombocytopenias vary in their presentation, associated features, and molecular etiologies. An accurate diagnosis is important to provide appropriate therapy as well as counseling for the individual and their family members. As the genetic basis of more disorders is understood, it will be possible to diagnose a greater fraction of patients as well as learn more about the process of megakaryopoiesis and platelet production.

Adult post-traumatic radioulnar synostosis.

Post-traumatic radioulnar synostosis is a rare complication of forearm fracture. Resulting in loss of forearm axial rotation, it is functionally very disabling. The surgical indication, timing of operation, surgical technique, interest and type of adjuvant treatment are all issues with which physicians managing radioulnar synostosis must deal. No therapeutic consensus yet exists, but a wide variety of surgical techniques and adjuvant treatments are suggested. A literature review sought to identify risk factors for synostosis, with a view to prevention and determining a suitable therapeutic attitude in the light of existing data.

Talonavicular synostosis with lateral ankle instability--A case report and review of the literature.

Talonavicular coalition is a rare autosomal recessive congenital anomaly that is usually asymptomatic and detected incidentally on radiographs. It is associated with symphalangism, clinodactyly, a great toe that is shorter than the second toe, clubfoot, calcaneonavicular coalition, talocalcaneal coalition and a ball-and-socket ankle joint. The authors present a review of the literature and case report of a patient with complete osseous talonavicular coalition, talocalcaneal coalition and lateral ankle instability which was successfully treated with subtalar fusion and lateral ligament reconstruction.