Raine syndrome: Prenatally identified severe craniofacial phenotype with multisuture synostosis and brain abnormalities associated with variants in FAM20C.

Raine syndrome (MIM 259775) is a rare autosomal recessive disorder, first described by Raine et al. in 1989, with an estimated prevalence of <1/1,000,000. This is due to pathogenic variants in FAM20C characterized by osteosclerosis, typical craniofacial features, and brain calcifications. Here, we report a novel variant in FAM20C, describe a uniquely severe craniofacial and CNS phenotype of Raine syndrome, and correlate it with prenatal findings. Fetal phenotyping was based on ultrasound and MRI. Solo exome sequencing was performed from DNA extracted from postmortem skin biopsy. Targeted parental variant testing was subsequently performed. A homozygous missense variant NM_020223.4 (c.1445 G > A (p.Gly482Glu)) was identified in FAM20C associated with Raine syndrome. The infant had the characteristic dysmorphic features seen in Raine syndrome. He had particularly significant CNS manifestations consisting of multisuture craniosynostosis with protrusion of the brain parenchyma through fontanelles and cranial lacunae. Histological sections of the brain showed marked periventricular gliosis with regions of infarction, hemorrhage, and cavitation with global periventricular leukomalacia. Numerous dystrophic calcifications were diffusely present. Here, we demonstrate the identification of a novel variant in FAM20C in an infant with the characteristic features seen in Raine syndrome. The patient expands the characteristic phenotype of Raine syndrome to include a uniquely severe CNS phenotype, first identified on prenatal imaging.

Fetal hydrops caused by a novel pathogenic MECOM variant.

We report a fetus with hydrops, congenital heart disease and bilateral radioulnar synostosis caused by a novel pathogenic MECOM variant. The female fetus was referred for post-mortem examination after fetal hydrops and intrauterine death was diagnosed at 20 weeks gestation. Post-mortem examination confirmed fetal hydrops, pallor, truncus arteriosus and bilateral radioulnar synostosis. Trio whole genome sequencing analysis detected a novel de novo heterozygous pathogenic loss-of-function variant in MECOM (NM_004991), associated with a diagnosis of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia 2 (RUSAT-2). RUSAT-2 is a variable condition associated postnatally with bone marrow failure, radioulnar synostosis and congenital anomalies. RUSAT-2 is not currently associated with a prenatal phenotype or fetal demise, and was not present on diagnostic NHS prenatal gene panels at time of diagnosis. This case highlights the diagnostic value of detailed phenotyping with post-mortem examination, and of using a broad sequencing approach.

Outcomes of surgical management for tarsal coalitions: a systematic review.

PURPOSE: To analyze the outcome of surgical treatment of tarsal coalition, assess the role of the surgical technique, as well as of coalition size and type on outcomes. METHODS: The search followed the Preferred Reporting Items of Systematic Review and Meta-Analysis and was performed in four databases: MEDLINE, Central, Scopus and Web of Science. The protocol has been registered in the international prospective register of systematic reviews. Patient-reported outcomes (PROMs), complications, revisions and radiographic recurrence were collected. Risk of bias was assessed using MINORS criteria. A random-effects model for meta-analysis was applied for analysis of data heterogeneity. RESULTS: Twenty-five studies including 760 tarsal coalitions were included and had a weighted average follow-up of 44 months. Studies scored fair to poor on the risk of bias assessment with a mean MINORS score of 67% (44-81%). In 77.8% (37.5-100%) of surgically treated tarsal coalitions, good/excellent/non-limiting or improved PROMs were reported. Calculated data heterogeneity was moderate (I2 = 57%). Open bar resection with material interposition had a clinical success rate of 78.8% (50-100%). Complications occurred in 4.96% of cases. Coalition size did not prove to be a determining factor in postoperative outcome. The influence of the coalition type was not investigated by any of the studies. CONCLUSION: Data on outcomes of surgical management for tarsal coalitions is limited to retrospective case series with high risk of bias and moderate data heterogeneity. In about ¾ of cases, open resection and interposition of material results in improved PROMs. The arbitrary margin of ≥ 50% of TC coalition size in relation to the posterior facet has little importance in surgical decision-making. None of the studies reported on the influence of the coalition type on postoperative clinical success.

Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2.

Roberts syndrome (also known as Roberts-SC phocomelia syndrome) is an autosomal recessive developmental disorder, characterized by pre- and postnatal growth retardation, limb malformations including bilateral symmetric tetraphocomelia or mesomelia, and craniofacial dysmorphism. Biallelic loss-of-function variants in ESCO2, which codes for establishment of sister chromatid cohesion N-acetyltransferase 2, cause Roberts syndrome. Phenotypic spectrum among patients is broad, challenging clinical diagnosis in mildly affected individuals. Here we report a 3-year-old boy with a mild phenotype of Roberts syndrome with bilateral elbow contractures, humeroradial synostosis, mild lower limb disparity, and facial dysmorphism. Trio whole-exome sequencing identified the novel biallelic splice variant c.1673+1G>A in ESCO2 in the patient. Aberrant ESCO2 pre-mRNA splicing, reduced relative ESCO2 mRNA amount, and characteristic cytogenetic defects, such as premature centromere separation, heterochromatin repulsion, and chromosome breaks, in patient cells strongly supported pathogenicity of the ESCO2 variant affecting one of the highly conserved guanine-thymine dinucleotide of the donor splice site. Our case highlights the difficulty in establishing a clinical diagnosis in individuals with minor clinical features of Roberts syndrome and normal intellectual and social development. However, next-generation sequencing tools allow for molecular diagnosis in cases presenting with mild developmental defects.

Multiple synostoses syndrome: Clinical report and retrospective analysis.

Multiple synostoses syndrome (SYNS1; OMIM# 186500) is a rare autosomal dominant disorder reported in a few cases worldwide. We report a Chinese pedigree characterized by proximal symphalangism, conductive hearing loss, and distinctive facies. We examined the genetic cause and reviewed the literature to discuss the pathogeny, treatment, and prevention of SYNS1. Audiological, ophthalmological, and radiological examinations were evaluated. Whole-exome sequencing (WES) was performed to identify mutations in the proband and her parents. Sanger sequencing was used to verify the results for the proband, parents, and grandmother. The literature on the genotype-phenotype correlation was reviewed. The patient was diagnosed with multiple synostoses syndrome clinically. WES and bioinformatic analysis revealed a novel missense mutation in the NOG gene, c.554C>G (p.Ser185Cys), cosegregated in this family. The literature review showed that the phenotype varies widely, but the typical facies, conductive hearing loss, and proximal symphalangism occurred frequently. All reported mutations are highly conserved in mammals based on conservation analysis, and there are regional hot spots for these mutations. However, no distinct genotype-phenotype correlations have been identified for mutations in NOG in different races. Regular systematic examinations and hearing aids are beneficial for this syndrome. However, the outcomes of otomicrosurgery are not encouraging owing to the regrowth of bone. This study expanded the mutation spectrum of NOG and is the first report of SYNS1 in a Chinese family. Genetic testing is recommended as part of the diagnosis of syndromic deafness. A clinical genetic evaluation is essential to guide prevention, such as preimplantation genetic diagnosis.

Intradiploic Hematoma Associated With Synostosis in an Infant.

Intradiploic hematomas are extremely rare, particularly in newborns. Caused by bleeding between the inner and outer tables of the calvarium, they manifest with bony swelling of the skull. The authors present the first case of an intraosseous hematoma associated with synostosis, and the first report in a female patient. The clinical, radiological, surgical, and pathological characteristics of this lesion are discussed.

Carpal Coalitions on Radiographs: Prevalence and Association With Ordering Indication.

PURPOSE: Carpal coalitions are common and usually incidental to the indication for wrist radiographs. It is not clear if, or when, carpal coalitions cause pain. The aim of this study was to assess the prevalence of incidental carpal coalitions by evaluating radiographs taken for various indications and to test the association of demographic variables and ordering indications with the finding of a carpal coalition. METHODS: We reviewed 1,119 posteroanterior wrist radiographs for the presence of carpal coalition. We used bivariate and multivariate analyses to assess demographic factors for their independent associations with the presence of carpal coalitions and to compare the difference in the prevalence of carpal coalitions between radiographs obtained to evaluate traumatic wrist pain (623 wrists), nontraumatic wrist pain (175 wrists), and other reasons (321 wrists). RESULTS: Radiographs of 98 out of 1,119 patients (8.8%) showed a carpal coalition. Carpal coalitions were equally likely on radiographs obtained for traumatic wrist pain and nontraumatic wrist pain. Patients with no wrist trauma or wrist pain were less likely to have a carpal coalition on their radiograph. CONCLUSIONS: We consider carpal coalitions an unlikely cause of wrist pain. The lower prevalence in radiographs obtained for causes other than wrist trauma or wrist pain remains unexplained, although it may be spurious. In the evaluation of a patient with nonspecific wrist pain, clinicians should be careful ascribing symptoms to anatomical variations on radiographs. These incidental findings should not usually affect management. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

[Surgical treatment of talocalcaneal coalition : Experience with 80 cases of pediatric or adolescent patients]. / Operative Behandlung der Coalitio talocalcanearis : Erfahrungen aus 80 Fällen kindlich-jugendlicher Patienten.

INTRODUCTION: There is still a controversial discussion on the treatment of talocalcaneal coalition with and without planovalgus deformity. From 2002-2014 80 cases of talocalcaneal coalition in children and adolescents under 18 years of age were surgically treated by J. Hamel. The objective of this study is a retrospective analysis, especially of unfavourable results. METHODS: Patients with minimum follow up of 12 months were included (35.7 months on average). In 31 cases treatment consisted of resection and fat-grafting (group 1), in 26 additional cases tarsal osteotomy was added because of planovalgus-deformity (group 2), and in 23 cases primary fusion of the talocalcaneal joint was performed (group 3). RESULTS: In group 1 one patient was lost to follow-up early with a severe peroneal spasticity and unknown further course. Two further patients still had remarkable pain after 15 months, and another patient had to undergo secondary fusion because of persistent pain. In group 2 secondary fusion was undertaken in two cases and offered in four other cases. In group 3 two patients still suffered from moderate tarsal pain, although complete fusion occurred; one of these patients underwent bilateral treatment. All other patients were pain free or nearly pain free on the last follow-up visit, with marked improvement in comparison to the preoperative situation. DISCUSSION: Surgical treatment of talocalcaneal coalition is successful in most cases in the short to medium follow-up, but unfavourable results are not uncommon and may require secondary fusion. Differential indication between resection, additional deformity correction, or primary fusion seems to be most important.

Patient-reported Outcomes of Tarsal Coalitions Treated With Surgical Excision.

PURPOSE: There are little patient-reported data on functional outcomes of tarsal coalition resection in children and adolescents. The purpose of this study is to evaluate the medium-term (>2 y) outcomes in patients who have had surgical excision of their symptomatic tarsal coalition and to compare patient-based outcomes in patients who have calcaneonavicular (CN) coalitions to those with talocalcaneal (TC) coalitions. METHODS: A billing query was conducted to identify patients who had surgical excision of their tarsal coalition between 2003 and 2008. Eligible patients were mailed questionnaires consisting of a modified American Orthopaedic Foot and Ankle Society (AOFAS) score and the University of California at Los Angeles (UCLA) activity scale. Patients were also specifically asked if their activity level was limited by their foot pain. Only patients who returned questionnaires were included. Demographics and diagnostic images were reviewed. A nonresponder analysis was completed. Complications such as infection and reoperation were reported. RESULTS: Sixty-three patients (22 females, 41 males) who returned questionnaires were included in the analysis. Twenty-four patients had bilateral surgery. TC coalitions were present in 20 patients (32%); CN coalitions were present in 43 patients (68%).Overall, mean modified AOFAS score was 88.3 and mean UCLA activity score was 8.33 at an average of 4.62 years after surgery. Patients who had TC coalitions had similar modified AOFAS scores (88.4) and UCLA activity scores (8.4) when compared with those with CN coalitions (88.0 and 8.3, both not significant).Of the 73% (46/63) patients who reported that their activity levels were not limited by their foot pain, the mean AOFAS score was 93.9 and the mean UCLA activity score was 8.9; 32 of these were CN and 14 were TC coalitions. Of the 27% (17/63) patients who reported that their activity levels were limited by their foot pain, the mean AOFAS score was 72.9 and the mean UCLA activity score was 6.9; 11 of these were CN and 6 were TC coalitions. There was a statistically significant difference in these groups both in modified AOFAS score (P<0.0001) and UCLA activity score (P=0.006). There was no difference in outcomes between those who were treated for a TC and CN coalition. CONCLUSIONS: Patient-reported outcomes after surgical excision of tarsal coalition reveal that >70% of patients' activities are not limited by pain and their functional outcome is terrific. A few patients continue to have problems with ongoing foot pain and activity limitations. The type of coalition does not seem to be an indicative factor in determining outcome.

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.

Congenital radioulnar synostosis: is prenatal diagnosis possible? - A case report.

OBJECTIVES: The main objectives of this case report are to discuss prenatal ultrasound findings of congenital radioulnar synostosis and to review the literature. CASE REPORT: A patient was diagnosed with congenital radioulnar synostosis at eight months old when parents noticed limited motions in the child's left forearm. The parent denied any traumatic or family history of bony malformations. Physical examination by a pediatric orthopedics specialist and digital radiography revealed proximal radioulnar synostosis. The case report includes perinatal course, comparison between the postnatal radiography and fetal ultrasound images. CONCLUSION: Congenital radioulnar synostosis is often associated with sex chromosome abnormalities and congenital musculoskeletal disorders or syndromes affecting limbs. Isolated congenital radioulnar synostosis is hardly diagnosed before birth, in some cases even have been neglected postnatally. Knowing the developmental milestones of the forearm and specified high-risk groups might help develop a targeted screening strategy to increase the possibility of early detection and intervention.

Posttraumatic synostosis between the thyroid cartilage and the cervical spine causing dysphagia.

A 64-year-old man, 7 years after cervical trauma, presented with severe dysphagia of 3-month duration. Computed tomography showed an unusual synostosis between the thyroid cartilage and the cervical spine at C5-6-7 on the right side. A barium swallow study revealed no laryngeal elevation during swallowing. Surgical resection of the bony fusion was performed, and the patient's dysphagia immediately improved without any complications. We report a case of delayed synostosis between the thyroid cartilage and the cervical spine causing severe dysphagia 7 years after cervical trauma. Surgical resection of the bony fusion resulted in immediate improvement of the dysphagia.

Successful surgical treatment of mandibulo-zygomatic arch synostosis secondary to trauma in a dog.

This is a report of mandibulo-zygomatic arch synostosis in a dog 7 mo after trauma to the maxilla. Advanced diagnostic imaging was considered essential for characterization of the condition and treatment planning. Surgical excision of the bony proliferation and physiotherapy resulted in improved function within 6 wk.

Post-traumatic Radioulnar Synostosis in Distal Forearm Fractures in Children: A Report of 2 Cases.

CASES: Two pediatric cases of post-traumatic distal radioulnar synostosis are reported, accompanied by a literature review summarizing evidence on the management of these conditions. Radioulnar synostosis is a rare complication of distal forearm fractures, which impairs upper-extremity function. The numerous surgical procedures that have been described to treat this condition in adults typically involve synostosis resection and an interposition graft to reduce recurrence. The optimal treatment in children has not been established. CONCLUSIONS: Post-traumatic radioulnar synostoses are rare conditions in pediatric patients who can be successfully treated with surgical excision of the synostoses and without the use of interposition grafting.

Resection of Posttraumatic Rib Synostoses Resolves Pulmonary Insufficiency: A Case Report.

CASE: A 30-year-old woman underwent open reduction and internal fixation for multiple segmental rib fractures status post a motor vehicle collision. A year later, the patient presented with extensive intercostal heterotopic ossification associated with multilevel, hemithoracic, rib synostoses compromising her ventilation. The patient subsequently underwent synostoses excision and hardware removal. Pulmonary function tests (PFT), imaging, and patient-reported outcome scores demonstrate resolution of impairment. CONCLUSION: Resection of multilevel, intercostal, rib synostoses provided an effective treatment for pulmonary restrictive disorder secondary to traumatic rib synostosis. This is the first patient with documentation of prereconstructive and postreconstructive PFTs for chest wall synostosis excision.

Thoracic Outlet Syndrome with Subclavian Artery Thrombosis Caused by Synostosis of the First and Second Ribs: A Case Report.

CASE: A 43-year-old woman presented with pain, paresthesia, and coldness of the right upper extremity suggestive of the diagnosis of thoracic outlet syndrome. Three-dimensional computed tomography angiography revealed that the right subclavian artery was constricted because it traveled over an abnormal first rib. After anticoagulation and antithrombotic therapy, the patient underwent resection of the abnormal first rib. Postoperative angiography documented improvement over time of the poststenotic dilatation and recanalization of the subclavian artery capable of delivering almost normal distal flow. CONCLUSION: Arterial reconstruction is not always necessary for the treatment of arterial thoracic outlet syndrome associated with poststenotic dilatation of the subclavian artery.

Proximal tibiofibular synostosis as a possible cause of a pseudoradicular syndrome: a case report.

This paper presents a case report of persistent low back pain and suspected lumbar radiculopathy. A synostosis at the level of the proximal tibiofibular joint was diagnosed. After successful resection of the synostosis, the low back symptoms resolved completely. This is the first report of a proximal tibiofibular synostosis as a possible cause of referred pain proximally.