Radiohumeral Synostosis Research Articles

Special case of bilateral postaxial longitudinal deficiency in a 3-year-old child

Introduction: Considering the variety of their clinical, radiological, and etiological manifestations, congenital abnormalities of the upper limbs represent complex diseases. They can be separated into brachydactyly, duplication, differentiation failure, and training failure. Ulnar longitudinal deficiency, a deformity that belongs to the first group and is uncommon, manifests differently in the forearm and the hand. Postaxial longitudinal deficiency and unilateral radial humerus synostosis are common diagnoses. Case Report: We present a case of a 3-year-old boy who had radio-humeral synostosis on the right side along with a typical congenital failure of longitudinal bilateral ulnar development. Conclusion: While traditional radiography still plays a significant role in diagnosis and prognosis, ultrasonography and magnetic resonance imaging (MRI) will soon be valuable diagnostic tools. Each case is different, and the treatments and the time of surgery are specific, the optimal treatment remains the prosthetic door; however, the placement of a prosthetic on a sensitive member requires early intervention of the patient and his family.

Clinical manifestations and treatment of ulnar club hand

The medical records of 13 cases (16 limbs) diagnosed with ulnar club hand in Beijing Jishuitan Hospital between 1966 and 2016 were reviewed. The radiological characteristics of upper limb bones, the shape and function of shoulder, elbow, forearm, wrist, and hand were recorded. The surgical options include radial wedge osteotomy, ulnar anlage excision, release of syndactyly or narrowed first web, and release of camptodactyly were performed to correct deformities. The subjective evaluation of patients or their families was recorded. Thirteen patients with 16 affected limbs were identified with ulnar club hand. There were 7 males and 6 females with an average age of 12.4 years (range:1-29 years). Among them, 3 cases were bilateral, and 10 cases were unilateral. Six patients had right-side involvement and 4 patients had left-side involvement. Based on Bayne's classification, there were 4 type Ⅰ, 7 type Ⅱ, 4 type Ⅲ, and 1 type Ⅳ. The affected extremity was shorter than the normal limb. In patients with type Ⅰ deformity, the elbows were stable with normal range of motion, the wrists were stable with almost normal range of motion, and the hands were normal. In patients with type Ⅱ deformity, the stability of elbow was variable, and hand deformities were common. In patients with type Ⅲ deformity, the elbows were unstable, and hand deformities were common. The elbow of the patient with type Ⅳ deformity showed radiohumeral synostosis without hand deformity. Surgical treatment was performed on 9 limbs. Mean follow-up was 22.3 months(range: 8-48 months), the subjective evaluation of patients or their families was satisfactory or relatively satisfactory. The surgical treatments of ulnar club hand usually focus on correction of hand and forearm deformities. The surgical result is good.

Disorders of Sex Development.

Disorders of Sex Development.

Clinical, endocrinological, and molecular features of four Korean cases of cytochrome P450 oxidoreductase deficiency

PurposeCytochrome P450 oxidoreductase (POR) deficiency is a rare autosomal recessive disorder caused by mutations in the POR gene encoding an electron donor for all microsomal P450 enzymes. It is characterized by adrenal insufficiency, ambiguous genitalia, maternal virilization during pregnancy, and skeletal dysplasia. In this study, we investigated the clinical, hormonal, and molecular characteristics of patients with POR deficiency in Korea.MethodsThis study included four patients with POR deficiency confirmed by biochemical and molecular analysis of POR. Clinical and biochemical findings were reviewed retrospectively. Mutation analysis of POR was performed by Sanger sequencing after polymerase chain reaction amplification of all coding exons and the exon-intron boundaries.ResultsAll patients presented with adrenal insufficiency and ambiguous genitalia regardless of their genetic sex. Two patients harbored homozygous p.R457H mutations in POR and presented with adrenal insufficiency and genital ambiguity without skeletal phenotypes. The other two patients with compound heterozygous mutations of c.[1329_1330insC];[1370G>A] (p.[I444Hfs*6];[R457H]) manifested skeletal abnormalities, such as craniosynostosis and radiohumeral synostosis, suggesting Antley-Bixler syndrome. They also had multiple congenital anomalies involving heart, kidney, and hearing ability. All patients were treated with physiologic doses of oral hydrocortisone.ConclusionsWe report the cases of 4 patients with POR deficiency identified by mutation analysis of POR. Although the study involved a small number of patients, the POR p.R457H mutation was the most common, suggesting founder effect in Korea. POR deficiency is rare and can be misdiagnosed as 21-hydroxylase or 17α-hydroxylase/17,20-lyase deficiency. Therefore, molecular analysis is critical for confirmatory diagnosis.

Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency

Although POR deficiency (PORD) is assumed to be accompanied by excessive placental androgen accumulation and enhanced adrenal and testicular androgen production via the backdoor pathway as well as compromised testicular androgen production via the frontdoor pathway, there is no direct evidence for the flux of excessive placental androgens into the fetal circulation and for the production of dihydrotestosterone (DHT) via the backdoor pathway. We examined longitudinal serum and urine steroid metabolite profiles in a 46,XY infant with PORD who was prenatally identified because of the progressive fetal masculinization and maternal virilization from the mid-gestation and the presence of fetal radio-humeral synostosis and was confirmed to have compound heterozygous mutations of POR (p.Q201X and p.R457H). The results showed (1) markedly and inappropriately elevated serum androstenedione and testosterone (T) values at birth, (2) a markedly increased serum DHT value with a normal DHT/T ratio at birth, (3) transient elevation of serum T and DHT values accompanied by a normal DHT/T ratio and concomitant elevations of intermediate steroid metabolites on both the frontdoor and backdoor pathways at 30 days of age, and (4) persistent PORD-compatible urine steroid profiles. Although the data obtained from a single infantile patient are too premature to be generalized, they imply: (1) the transfer of excessive placental androgens into the fetal as well as the maternal circulations from the mid-gestation, (2) lack of a clinically discernible amount of DHT production via the adrenal backdoor pathway around birth, and (3) the activation of both the frontdoor and backdoor pathways in the testis around the mini-puberty, with no production of a clinically discernible amount of DHT via the testicular backdoor pathway.

Agenesis of the Corpus Callosum and Skeletal Deformities in Two Unrelated Patients: Analysis via MRI and Radiography

Purpose. Mental retardation, mild to severe epilepsy and cerebral palsy often of hemiplegic type are common accompaniments in patients with agenesis/hypoplasia of the corpus callosum. Skeletal deformities of bilateral radiohumeral synostosis, brachydactyly, bilateral elbow dislocation, talipes equinovarus, and juxtacalcaneal accessory bones have been encountered in two unrelated children with agenesis of the corpus callosum. Methods. We report on two unrelated children who presented with the full clinical criteria of agenesis of the corpus callosum. Strikingly, both presented with variable upper and lower limb deformities. The clinical features, radiographic and MRI findings in our current patients, have been compared with previously reported cases identified through a PubMed literature review. Results. Bilateral radiohumeral synostosis associated with pyruvate dehydrogenase deficiency has been encountered in one patient. The other patient manifested bilateral elbow dislocation, coxa valga, talipes equinovarus, and bilateral juxtacalcaneal accessory bones. Conclusion. The constellation of malformation complexes in our current patients have the hitherto not been reported and expanding the spectrum of skeletal deformities in connection with agenesis of the corpus callosum.

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.

A Report of Two cases of Al-Awadi Raas-Rothschild Syndrome (AARRS) supporting that “Apparent” Phocomelia differentiates AARRS from Schinzel Phocomelia Syndrome (SPS)

Although there is a long list of syndromes with phocomelia, there are only two syndromes in which there is concurrent pelvic dysplasia and phocomelia: Al-Awadi–Raas-Rothschild syndrome (AARRS) and Schinzel phocomelia syndrome (SPS). Currently, there is a diagnostic confusion between the two syndromes and both have the same MIM entry (MIM 276820). We believe that the two syndromes are different entities and we also believe that the limb defect in SPS is a “true” phocomelia while the limb defect in AARRS is an “apparent” phocomelia. “Apparent” phocomelia describes the most severe form of ulnar ray deficiency in which there is absent ulna with radio-humeral synostosis. “Apparent” phocomelia is diagnosed radiologically by three radiological features: the apparently single bone occupying the arm/forearm appears relatively long, the area of radio-humeral synostosis will have thicker cortex with or without slight angulation, and the lower end of the bone resembles the lower end of a radius and not a humerus. In this paper, we present two new cases of AARRS from two different Saudi Arabian tribes: one case with R292C mutation of WNT7A with bilateral “apparent” phocomelia and a second case with a novel c.814G>T mutation of the WNT7A gene (resulting in wnt7a protein truncation at position 272) with unilateral “apparent” phocomelia. We reviewed previously reported cases of AARRS and SPS to further delineate the differences between these two syndromes. We make the argument that these two syndromes are two different entities and hence require two different MIM entries.

Anesthetic Risks Associated With Antley-Bixler Syndrome

Antley-Bixler syndrome is an autosomal recessive disorder characterized by multiple bone and cartilaginous abnormalities. The main features of this syndrome include brachycephaly, midface hypoplasia, dysplasia of ears and nose, radiohumeral synostosis, choanal stenosis, or atresia. Distinctive features are based on craniofacial deformity and humeroradial synostosis. In this report, we describe the anesthesia management of a 20-year-old Antley-Bixler syndrome patient who underwent maxillary advancement via Le Fort I osteotomy. During surgical management of craniofacial syndrome patients, particularly Antley-Bixler syndrome, the whole surgical team should be aware of possible deformities involving the airway, which may be underestimated or nondetected prior to surgery. These deformities including choanal atresia/stenosis may lead to failure of nasotracheal intubation and mask ventilation, therefore jeopardizing the surgical procedure and/or patient safety. Accurate preoperative preparation and being aware of the components of this syndrome is vital to eliminate respiratory complications and enable uneventful anesthetic and surgical management.

Antley–Bixler-Syndrome – Staged management of craniofacial malformations from birth to adolescence – A case report

In 1975 Antley and Bixler described an unusual syndromal disorder consisting of complex craniosynostosis with midfacial hypoplasia, dysplasia of ears and nose, radiohumeral synostosis, congenital fractures of the femur and upper airway impairment in a newborn. Additional urogenital and cardiac malformations can be associated however diagnosis is based on a characteristic craniofacial deformity in association with humeroradial synostosis. Complex disturbance of craniofacial growth due to premature synostoses of the cranial base and vault results in a characteristic phenotype. Steroidogenesis due to intrinsic or extrinsic disturbance by maternal fluconazole ingestion during early pregnancy may be impaired. The mode of inheritance is supposed to be autosomal recessive. Mutations in the fibroblast growth factor receptor 2 (FGFR2) as well as mutations in the cytochrome P450 oxidoreductase (OR) gene have been verified. Like in other craniofacial dysostosis syndromes malformation of neuro- and viscerocranium is complex and requires a staged age- and growth-related interdisciplinary management with respect to the individual situation. This case report of a female patient born in 1994 suffering from that rare syndrome describes the interdisciplinary long-term management in one craniofacial centre over 16 years from birth to adolescence.

Spectrum of Antley-Bixler Syndrome

Antley-Bixler syndrome (ABS) is an exceptionally rare craniosynostosis syndrome characterized by radiohumeral synostosis present from the perinatal period. There is a wide spectrum of anomalies seen within ABS, and other features include midface hypoplasia; choanal stenosis or atresia; multiple joint contractures; visceral anomalies, particularly of the genitourinary system; and impaired steroidogenesis. The condition of ABS is curious in that mutations of 2 separate genes have been identified and that there seem to be subtle phenotypic differences between the 2 genotypes. Mutations of the P450 oxidoreductase gene have been reported in those patients with genital anomalies and/or impaired steroidogenesis, and the S351C mutation of the fibroblast growth factor receptor 2 gene has been reported predominantly in those patients with normal genitalia and steroidogenesis. We report a series of 4 patients with ABS and review their main findings and management.

Did Akhenaten Have the Antley–Bixler Syndrome?

Letters15 December 2009Did Akhenaten Have the Antley–Bixler Syndrome?Walter L. Miller, MDWalter L. Miller, MDFrom University of California, San Francisco, San Francisco, CA 94143.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-12-200912150-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Braverman and colleagues (1) hypothesize that Akhenaten (Amenophis IV) had gynecomastia and brachycephaly attributable to the form of the Antley–Bixler syndrome (ABS) caused by mutations in P450 oxidoreductase (POR). Having reviewed the clinical findings and identified the genetic defects in most reported cases of POR deficiency (2–4), I find this unlikely. First described in 1975, ABS is a rare skeletal dysplasia syndrome characterized by craniosynostosis, radioulnar or radiohumeral synostosis, brachycephaly, femoral bowing, femoral fractures, midface hypoplasia, proptosis, a “pear-shaped” nose, choanal atresia, and other bony findings (5, 6). The ABS phenotype can result from either of 2 ...

A case of Antley-Bixler syndrome caused by compound heterozygous mutations of the cytochrome P450 oxidoreductase gene

Antley-Bixler syndrome (ABS) is a skeletal malformation syndrome primarily affecting the skull and limbs. Although causal mutations in the FGFR2 gene have been found in some patients, mutations in the electron donor enzyme P450 oxidoreductase gene (POR) have recently been found to cause ABS in other patients. In addition to skeletal malformations, POR deficiency also causes glucocorticoid deficiency and congenital adrenal hyperplasia with ambiguous genitalia in both sexes. Here, we report on a 7-month-old Korean girl with ABS and ambiguous genitalia who was confirmed by POR gene analysis. Our patient showed typical skeletal findings with brachycephaly, mid-face hypoplasia, and radiohumeral synostosis. She also had partial labial fusion and a single urogenital orifice, as well as increased 17alpha-hydroxyprogesterone levels, suggesting a 21-hydroxylase deficiency. Cortisol and DHEA-sulfate response to rapid adrenocorticotropic hormone (ACTH) stimulation was inadequate. Direct sequencing of the POR gene revealed compound heterozygous mutations (I444fsX449 and R457H). This is the first report of a Korean patient with ABS caused by POR gene mutations.

Foot anomalies in Antley–Bixler syndrome: three case reports

Multiple joint contractures, including radiohumeral synostosis, are the hallmark of Antley-Bixler syndrome (ABS). The detailed description of the skeletal aberration, however, focused in feet is scarce. We carried out the scrutiny for foot lesion in three ABS patients with POR (nicotinamide adenine dinucleotide phosphate-oxidase-cytochrome P450 oxidoreductase) gene mutations, one of whom had undergone surgical intervention for difficulty in walking. Radiographs in all three patients showed middle cuneiform-second metatarsal synostosis and the fourth brachymetapody, irrespective of the severity of their systemic manifestations. In addition, talocalcaneal synostosis, lateral cuneiform-cuboid synostosis, defects of middle phalanx, and distal phalanx-middle phalanx synostosis were found in at least two patients. In conclusion, we found distinctive constellations of foot abnormalities in the patients of ABS with POR gene mutation, which may be useful in planning the treatment strategy, as well as in the diagnostic process.

Clinical Manifestations of Type IV Ulna Longitudinal Dysplasia

Ulna longitudinal dysplasia is an uncommon congenital anomaly that demonstrates a wide variety of clinical manifestations. The clinical manifestations and function of patients with Bayne type IV ulna longitudinal dysplasia have not been well characterized. The purpose of this study was to report the clinical features of type IV ulna longitudinal dysplasia and the extent to which this affects a patient's ability to perform activities of daily living. The medical records of children diagnosed with ulna longitudinal dysplasia in our institution between 1960 and 2004 were reviewed. The children found to have ulna longitudinal dysplasia with radiohumeral synostosis (Bayne type IV ulna dysplasia) were studied. The laterality of the deformity, associated musculoskeletal and nonmusculoskeletal anomalies, and treatments were recorded. Patients were interviewed regarding their ability to perform activities of daily living. One hundred twenty-five patients with 146 affected limbs were identified with ulna dysplasia. Seventeen limbs in 14 patients (12% of affected limbs) demonstrated radiohumeral synostosis (RHS). Three of 14 patients with RHS had bilateral involvement. The elbows were fixed in 20 degrees to 90 degrees of flexion. No elbows were positioned in full extension. Eleven of the 17 involved limbs with RHS had digital anomalies. Nine of the 17 limbs had surgical reconstruction. The majority of these procedures were performed on the hand. The elbow, forearm, wrist, and hand clinical findings associated with type IV ulna longitudinal dysplasia are variable. Surgical treatment usually focuses on correction of hand abnormalities. Many patients function satisfactorily and are able to perform daily activities without surgical intervention.

Otologic findings in Antley–Bixler syndrome: A clinical and radiologic case report

Antley-Bixler syndrome (ABS) is characterized by craniofacial dysmorphism and radiohumeral synostosis with other associated anomalies. Prior studies have commonly described the entirety of the syndrome or the genetic abnormalities underlying the syndrome, however, no study has specifically addressed the otologic findings of ABS. We present a case of ABS, specifically focusing on the otologic ramifications of the disease, and provide recommendations for approaching the otologic management of these complex patients.

Proximal Femoral Focal Deficiency as a Manifestation of Antley-Bixler Syndrome: A Case Report

We report a case of the Antley-Bixler syndrome in an 11-year-old girl. She presented with bilateral proximal femoral focal deficiency, right clubfoot, left radiohumeral synostosis, bilateral ear hypoplasia, cleft palate, tongue tie, missing teeth, congenital heart disease, a pelvic kidney with hydronephrosis, and mental retardation. Proximal femoral focal deficiency has never been reported before as a manifestation of Antley-Bixler syndrome. Her mother was exposed to radiation during an intravenous urogram done in the first trimester of pregnancy. Exposure to radiation has not been implicated as a cause of Antley-Bixler syndrome.

Linking Antley–Bixler syndrome and congenital adrenal hyperplasia: A novel case of P450 oxidoreductase deficiency

The Antley-Bixler syndrome (ABS) is a multiple congenital malformation syndrome with craniosynostosis, radiohumeral synostosis, femoral bowing, choanal atresia or stenosis, joint contractures, urogenital abnormalities and, often, early death. Autosomal recessive and dominant inheritance have been postulated, as has fluconazole teratogenesis. Mutations in POR (P450 (cytochrome) oxidoreductase, an essential electron donor to enzymes participating in cholesterol biosynthesis), have been identified in some patients with the ABS phenotype. Recent evidence suggests that these mutations cause attenuated steroid hydroxylation, which in turn, causes congenital adrenal hyperplasia (CAH) with ambiguous genitalia in both sexes and glucocorticoid deficiency. Here, we report on a new patient with findings of both ABS and CAH that further illustrates how low maternal estriol at prenatal screening can serve as a marker steroid facilitating early diagnosis.

Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients.

We report on molecular and clinical findings in 10 Japanese patients (four males and six females) from eight families (two pairs of siblings and six isolated cases) with Antley-Bixler syndrome accompanied by abnormal genitalia and/or impaired steroidogenesis. Direct sequencing was performed for all the 15 exons of cytochrome P450 oxidoreductase gene (POR), showing two missense mutations (R457H and Y578C), a 24-bp deletion mutation resulting in loss of nine amino acids and creation of one amino acid (L612_W620delinsR), a single bp insertion mutation leading to frameshift (I444fsX449), and a silent mutation (G5G). R457H has previously been shown to be a pathologic mutation, and computerized modeling analyses indicated that the 15A>G for G5G could disturb an exonic splicing enhancer motif, and the remaining three mutations should affect protein conformations. Six patients were compound heterozygotes, and three patients were R457H homozygotes; no mutation was identified on one allele of the remaining one patient. Clinical findings included various degrees of skeletal features, such as brachycephaly, radiohumeral synostosis, and digital joint contractures in patients of both sexes, normal-to-poor masculinization during fetal and pubertal periods in male patients, virilization during fetal life and poor pubertal development without worsening of virilization in female patients, and relatively large height gain and delayed bone age from the pubertal period in patients of both sexes, together with maternal virilization during pregnancy. Blood cholesterol was grossly normal, and endocrine studies revealed defective CYP17A1 and CYP21A2 activities. The results suggest that Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis is caused by POR mutations, and that clinical features are variable and primarily explained by impaired activities of POR-dependent CYP51A1, CYP17A1, CYP21A2, and CYP19A1.

Correction of Facial Deformity Using a Red III Device in a Patient With Antley-Bixler Syndrome

Antley-Bixler syndrome was first described in 1975 and to date at least 44 cases have been reported. In addition to brachycephaly, this syndrome is associated with midface hypoplasia, bilateral radiohumeral synostosis, multiple joint contractures, long bone fractures, dysplastic ears, "pear shaped" nose, and occasionally urogenital or cardiac defects. The authors report a case in a 23-year-old man with severe midface deficiency treated using distraction osteogenesis. A modified Le Fort III osteotomy was performed, and nasal subunit and remaining Le Fort III segment was distracted separately. The classic RED II design was found to be insufficient, so the authors added an extra horizontal bar to the system and converted it to a RED III design. Midface advancement was 11 mm from the porion to the orbitale and 31 mm at point A. Nasal advancement at the nasal root level was 5 mm. There were no complications, and at 4 months after surgery, advancement was stable without any relapse.