Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by progressive osteolysis involving the carpal and tarsal bones, and often associated with nephropathy. It is caused by heterozygous mutation in the MAF bZIP transcription factor B (MAFB) gene. Heterogeneous clinical manifestation and wide spectrum of disease severity have been observed in patients with MCTO. Here, we report a case of a male patient who presented with kidney failure in childhood with progressive disabling skeletal deformity. He was diagnosed with MCTO at 31-years-old, where a de novo pathogenic heterozygous variant in NM_005461.5:c.212C>A: p.(Pro71His) of the MAFB gene was identified. While there has been little data on the long-term prognosis and life expectancy of this disease, this case report sheds light on the debilitating disease course with multiple significant morbidities of a patient with MCTO throughout his lifetime of 33 years.

The Greulich-Pyle (GP) and Tanner-Whitehouse 3 (TW3) methods are two common methods for assessing bone age (BA). The applicability of these methods for populations other than those in the United States and Europe has been questioned. Thus, this study tested the applicability of these methods for Taiwanese children.
In total, 1476 radiographs (654 boys, 822 girls) were analyzed. A subset of 200 radiographs was evaluated to determine intrarater and interrater reliability and the time required to yield a BA assessment. BA was determined by two reviewers using the GP method and two of the TW3 methods (the Radial-Ulnar-Short bones [RUS] method and the carpals method [Carpal]). The GP and TW3 methods were directly compared using statistical techniques. A subgroup analysis by age was performed to compare BA and chronological age using a paired t test for each age group.
The average times required to yield an assessment using the GP and TW3-RUS methods were 0.79 ± 0.14 and 3.01 ± 0.84 min (p < 0.001), respectively. Both the intrarater and interrater correlation coefficients were higher for the GP method (0.993, 0.992) than the TW3-RUS (0.985, 0.984) and TW3-Carpal (0.981, 0.973) methods. The correlation coefficient for the GP and TW3-RUS methods was highest in the pubertal stage (0.898 for boys and 0.909 for girls). The mean absolute deviations for the GP and TW3-RUS methods in the pubertal stage were 0.468 years (boys) and 0.496 years (girls). Both the GP and TW3-Carpal methods underestimated BA for boys in the prepubertal stage. Both the GP and TW3-RUS methods overestimated BA for girls in the pubertal and postpubertal stages.
The GP and TW3-RUS methods exhibit strong agreement in the pubertal and postpubertal stages for both sexes. With appropriate adjustments based on Taiwanese data, both methods are applicable to our children.

Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene.
Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein.
The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.

Analyze the clinical and genetic characteristics of a rare Chinese family with Multiple synostoses syndrome and identify the causative variant with the high-throughput sequencing approach.
The medical history investigation, physical examination, imaging examination, and audiological examination of the family members were performed. DNA samples were extracted from the family members. The candidate variant was identified by performing whole-exome sequencing of the proband, then verified by Sanger sequencing in the family.
The family named HBSY-018 from Hubei province had 18 subjects in three generations, and six subjects were diagnosed with conductive or mixed hearing loss. Meanwhile, characteristic features including short philtrum, hemicylindrical nose, and hypoplastic alae nasi were noticed among those patients. Symptoms of proximal interdigital joint adhesion and inflexibility were found. The family was diagnosed as Multiple synostoses syndrome type 1 (SYNS1).The inheritance pattern of this family was autosomal dominant. A novel mutation in the NOG gene c.533G>A was identified by performing whole-exome sequencing of the proband. The substitution of cysteine encoding 178th position with tyrosine (p.Cys178Tyr) was caused by this mutation, which was conserved across species. Co-segregation of disease phenotypes was demonstrated by the family verification.
The family diagnosed as SYNS1 was caused by the novel mutation (c.533G>A) of NOG. The combination of clinical diagnosis and molecular diagnosis had improved the understanding of this rare disease and provided a scientific basis for genetic counseling in the family.

OBJECTIVE: The purpose of this study is to construct an automatic carpal bone age evaluation system for Chinese children based on TW3-C Carpal method by deep learning and to evaluate the accuracies in test set and clinical test set.
METHODS: A total of 8184 radiographs of Chinese Han healthy children (2-14 years old) were collected from the 2005 China Skeletal Development Survey data and from the accumulated radiographs in bone age studies over the years. Three experienced radiologists and the China-05 standard maker jointly evaluated each bone development stage, and the consensual stage was decided as the reference standard. According to each epiphysis development stage, 10% of them were derived by stratified random sampling as test sets, and the remaining radiographs were used as training sets and validation sets. Furthermore, the overall performance of the model was estimated by comparing the mean difference, 95% limits of agreement, mean absolute difference (MAD) and root mean square (RMS) between the model predictions and the reference standard.
RESULTS: The percentage agreement of ratings in each epiphysis in the test set ranged from 82.82% to 90.06%, with an average of 86.94%. Compared with the reference standard, the automated bone age system has a mean difference of 0.01 years old, ± 0.45 years old in 95% confidence interval by single reading, an 85.93% percentage agreement of ratings, a 90.5% bone age accuracy rate, 0.20 years old of MAD, and 0.32 years old of RMS in the clinical test set.
CONCLUSIONS: The automatic bone age system for Chinese children has a comparable accuracy and stable determination compared with experienced radiologists.

The volar divergent dislocation of the second to fifth carpometacarpal joints and involving fracture of carpal is an extremely rare injury. We reported a case of 55-year-old man, victim of a motorbike, who was struck by a car, admitted at the emergency department unable to move his left hand with severe swelling. X-rays and CT scan showed a volar divergent dislocation of second to fifth carpometacarpal joints and involving fracture of carpal. Patient underwent closed reduction and plaster fixation right way, after one week, he received open reduction internal fixation with K-wire and plaster. Functional exercise was started progressively once K-wire and plaster were removed after six weeks. At six months follow-up, results were excellent and patient has regained all of his range of motion and hand activities. Key words: carpometacarpal joint, palmar, divergent, dislocation, hand, wrist.

The noggin protein encoded by the NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint development. The symptoms include abnormal skeletal development and conductive deafness.
In a retrospective study, clinical data of the proband and her family members, including 8 people and 50 healthy normal controls, were collected. Second-generation sequencing was performed on peripheral blood samples from them.
The sequencing analysis indicated that in the proband, the NOG gene had a c.532T > C, p.C178R (cytosine deletion, NM_005450.6:c.532T > C), leading to an amino acid change. The proband\'s father, grandmother, second sister, and third sister also had this mutation, whereas family members with normal phenotypes did not have the mutation.
Analysis of this family showed that the novel presentation of the c.532T > C, p.C178R mutation in the NOG gene resulted in syndrome-type autosomal dominant inheritance reflected in a mild clinical phenotype, which is of great importance for further studies of the clinical phenotype and pathogenesis of stapes sclerosis.

OBJECTIVE. The purpose of this study was to study changes in the median nerve, retinaculum, and carpal tunnel on MRI after successful endoscopic carpal tunnel release (ECTR). SUBJECTS AND METHODS. In this prospective study, 35 wrists in 32 patients (five men, 27 women; mean age, 56.7 ± 6.8 [SD] years) with nerve conduction test-confirmed primary carpal tunnel syndrome were evaluated from May 2013 to September 2016. Clinical scores ranging from 0 to 4 (no improvement to symptoms completely resolved) and MRI morphologic features of median nerve and carpal tunnel were evaluated at baseline and 3 and 12 months after ECTR. The paired t test was used to compare MRI parameters before and after ECTR and their relationships to clinical improvement scores. RESULTS. All patients\' conditions improved after ECTR with mean clinical improvement scores of 2.94 ± 1.0 at 3 months and 3.49 ± 0.56 at 12 months. Although median nerve swelling did decrease proximally, the nerve remained swollen (> 15 mm2) and flattened in all areas, even 12 months after ECTR. Additional changes occurred in median nerve caliber-change ratio, relative signal intensity, and carpal tunnel cross-sectional area. A retinacular gap was present in 33 (94%) wrists 3 months and six (17%) wrists 12 months after ECTR, and increased retinacular bowing persisted. CONCLUSION. After ECTR, undue swelling and flattening of the median nerve persist as long as 12 months after surgery, even in patients with a good surgical outcome. One should be wary of using these MRI findings as signs of persistent neural compression. The retinaculum reforms in most patients within 12 months of surgery but with a more bowed configuration.

Vascularized small-bone grafting is an efficient and often necessary surgical approach for nonunion or necrosis of several bones in particular sites of the body, including scaphoid, lunate, distal ulna, and clavicle. The medial femoral condyle is an excellent graft source that can be used in treating scaphoid, ulna, clavicle, or lower-extremity bone defects, including nonunion. Vascularized bone grafting to the small bones, particularly involving reconstruction of damaged cartilage surfaces, should enhance subchondral vascular supply and help prevent cartilage regeneration. Vascularized osteoperiosteal and corticoperiosteal flaps are useful for treating nonunion of long bones.

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.