OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Multiple synostoses syndrome type 1 (SYNS1). METHODS: Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were carried out for the proband and her parents. RESULTS: The pedigree has comprised of 14 members from three generations, of whom six had manifested hearing loss, with other symptoms including proximal symphalangism, hemicylindrical nose, amblyopia, strabismus, brachydactyly, incomplete syndactyly, which fulfilled the diagnostic criteria for SYNS1. WES had detected no pathogenic single nucleotide variants and insertion-deletion (InDel) in the coding region of the NOG gene, whilst copy number variation (CNV) analysis indicated that there was a heterozygous deletion involving the NOG gene. WGS revealed a heterozygous deletion (54171786_55143998) in 17q22 of the proband. The CNV was classified as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The heterozygous deletion in 17p22 involving the NOG gene probably underlay the pathogenesis of SYNS1 in this pedigree. Above finding has enriched the mutational spectrum of NOG. CNV should be considered when conventional sequencing has failed to detect any pathogenic variants in such patients.
Female ; Humans ; DNA Copy Number Variations ; East Asian People ; Pedigree ; Synostosis ; Phenotype

Intermetatarsal coalition (IC) is very rare; although few cases have been reported in foreign orthopedic journals, these have not originated in our country. We report the case of a 20-year-old man who complained of pain in the left forefoot only during long distance running (3 km). On examination, his foot shape, skin appearance, and gait were normal, with no plantar keratosis; however, the radiograph revealed coalition between the fourth and fifth metatarsals. Surgical excision was performed. In the histopathologic study, fibrous coalition was confirmed. This paper reports an uncommon case involving surgical excision of IC in the military service, involving active sport activity.
Foot ; Gait ; Humans ; Keratosis ; Metatarsal Bones ; Military Personnel ; Orthopedics ; Running ; Skin ; Sports ; Synostosis ; Young Adult

No abstract available.
Congenital Abnormalities* ; Foot* ; Metatarsal Bones* ; Synostosis*

Syndromic craniosynostosis has severe cranial stenosis and deformity, combined with hypoplastic maxillary bone and other developmental skeletal lesions. Among these various lesions, upper air way obstruction by hypoplastic maxillary bone could be the first life-threatening condition after birth. Aggressive cranial vault expansion for severely deformed cranial vaults due to multiple synostoses is necessary even in infancy, to normalize the intracranial pressure. Fronto-orbital advancement (FOA) is recommended for patients with hypoplastic anterior part of cranium induced by bicoronal and/or metopic synostoses, and posterior cranial vault expansion is recommended for those with flattening of the posterior part of the cranium by lambdoid synostosis. Although sufficient spontaneous reshaping of the cranium can be expected by expansive cranioplasty, keeping the cranial bone flap expanded sufficiently is often difficult when the initial expansion is performed during infancy. So far distraction osteogenesis (DO) is the only method to make it possible and to provide low rates of re-expansion of the cranial vault. DO is quite beneficial for both FOA and posterior cranial vault expansion, compared with the conventional methods. Associated hydrocephalus and chronic tonsillar herniation due to lambdoid synostosis can be surgically treatable. Abnormal venous drainages from the intracranial space and air way obstruction should be always considered at any surgical procedures. Neurosurgeons have to know well about the managements not only of the deformed cranial vault and the associated brain lesions but also of other multiple skeletal lesions associated with syndromic craniosynostosis, to improve treatment outcome.
Brain ; Congenital Abnormalities ; Constriction, Pathologic ; Craniosynostoses* ; Encephalocele ; Humans ; Hydrocephalus ; Intracranial Pressure ; Maxilla ; Osteogenesis, Distraction ; Parturition ; Skull ; Synostosis ; Treatment Outcome

Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction. Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of craniosynostosis. Nonsyndromic craniosynostosis accounts for more than 70% of all cases. Syndromic craniosynostosis with a certain genetic cause is more likely to involve multiple sutures or bilateral coronal sutures. FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1 genes are major causative genes of genetic syndromes associated with craniosynostosis. Although most of syndromic craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases. Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, and Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes. Saethre-Chotzen syndrome, Muenke syndrome, and craniofrontonasal syndrome are representative disorders showing isolated coronal suture involvement. Compared to the other types of craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic craniosynostosis.
Acrocephalosyndactylia ; Antley-Bixler Syndrome Phenotype ; Cranial Sutures ; Craniofacial Dysostosis ; Craniosynostoses* ; Diagnosis ; Genetic Counseling ; Humans ; Skull ; Sutures ; Synostosis ; Wills

Antley-Bixler syndrome (ABS) is a rare form of syndromic craniosynostosis with additional systemic synostosis, including radiohumeral or radioulnar synostosis. Another characteristic feature of ABS is mid-facial hypoplasia that leads to airway narrowing after birth. ABS is associated with mutations in the FGFR2 and POR genes. Patients with POR mutations present with either skeletal manifestations or congenital adrenal hyperplasia with ambiguous genitalia. We report here two cases of ABS caused by mutations in FGFR2 and POR. Although the patients had craniosynostosis and radiohumeral synostosis in common and cranioplasty was performed in both cases, the male with POR mutations showed an elevated level of 17α-hydroxyprogesterone during newborn screening and was diagnosed with congenital adrenal hyperplasia by adrenocorticotropic hormone stimulation. This patient has been treated with hydrocortisone and fludrocortisone. He had no ambiguous genitalia but had bilateral cryptorchidism. On the other hand, the female with the FGFR2 mutation showed severe clinical manifestations: upper airway narrowing leading to tracheostomy, kyphosis of the cervical spine, and coccyx deformity. ABS shows locus heterogeneity, and mutations in two different genes can cause similar craniofacial and skeletal phenotypes. Because the long-term outcomes and inheritance patterns of the disease differ markedly, depending on the causative mutation, early molecular genetic testing is helpful.
Adrenal Hyperplasia, Congenital ; Adrenocorticotropic Hormone ; Antley-Bixler Syndrome Phenotype* ; Coccyx ; Congenital Abnormalities ; Craniosynostoses ; Cryptorchidism ; Disorders of Sex Development ; Female ; Fludrocortisone ; Hand ; Humans ; Hydrocortisone ; Infant, Newborn ; Inheritance Patterns ; Kyphosis ; Male ; Mass Screening ; Molecular Biology ; Parturition ; Phenotype ; Population Characteristics ; Spine ; Synostosis ; Tracheostomy

Tarsal coalition is an abnormal union between two or more bones of the hind- and mid-feet, which can occur at various rates from cartilaginous to osseous union. Talonavicular coalition is reported less frequently than calcaneonavicular or talocalcaneal coalition and has been associated with various abnormalities, including symphalangism, clinodactyly, ray anomaly, clubfoot, other tarsal coalitions, and a ball-and-socket ankle joint. Patients with talonavicular coalitions are usually asymptomatic and rarely require surgical treatment. We review the literature and report on a case of 59-year-old male patient with talonavicular coalition.
Ankle Joint ; Clubfoot ; Humans ; Male ; Middle Aged ; Synostosis

Image-guided surgery potentially enhances intraoperative safety and outcomes in a variety of craniomaxillofacial procedures. We explore the efficiency of one intraoperative navigation system in a single complex craniofacial case, review the initial and recurring costs, and estimate the added cost (e.g., additional setup time, registration). We discuss the potential challenges and benefits of utilizing image-guided surgery in our specific case and its benefits in terms of educational and teaching purposes and compare this with traditional osteotomies that rely on a surgeon's thorough understanding of anatomy coupled with tactile feedback to blindly guide the osteotome during surgery. A 13-year-old presented with untreated syndromic multi-suture synostosis, brachycephaly, severe exorbitism, and midface hypoplasia. For now, initial costs are high, recurring costs are relatively low, and there are perceived benefits of imaged-guided surgery as an excellent teaching tool for visualizing difficult and often unseen anatomy through computerized software and multi-planar real-time images.
Adolescent ; Craniosynostoses ; Humans ; Osteotomy ; Surgery, Computer-Assisted* ; Synostosis

Adult ; Elbow Joint ; injuries ; Female ; Humans ; Joint Dislocations ; therapy ; Musculoskeletal Manipulations ; Radius ; abnormalities ; Radius Fractures ; therapy ; Synostosis ; therapy ; Ulna ; abnormalities

STUDY DESIGN: Retrospective case series. PURPOSE: To assess the effect of non-kyphotic aligned congenital C3-4 synostosis on the adjacent segment in 10 patients. OVERVIEW OF LITERATURE: In the cervical spine, fusion disease at the adjacent motion segments may be a risk factor for potential neurological compromise and death. METHODS: Radiograms of 10 patients 13 to 69 years of age presenting with neck/shoulder discomfort or pain with or without trauma history were examined. C3-4 synostosis was found incidentally in all patients on routine examination radiographs of cervical spine. RESULTS: Adjacent segment disease (ASD) was not found in the three patients younger than 39 years of age. Five of the 10 (50%) patients, including a 67-year-old man, did not develop spondylosis in any of the cervical mobile segments. Spondylosis was observed only in the caudal 1-2 mobile segments in the remaining five patients. The youngest was a 40-year-old male who had spondylosis in the two caudal mobile segments (C4-5 and C5-6). Spondylosis was limited to the two close caudal mobile segments and was not in the cranial segments. Flaring of the lower part of synostotic vertebra associated with advanced narrowed degenerate disc was evident in five patients. CONCLUSIONS: Mobile segment spondylosis in the individuals with congenital monosegment C3-4 synostosis over age of 40 years may be a natural manifestation of aging and is not solely an adjacent segment disease directly and fully related with congenital C3-4 synostosis.
Adult ; Aged ; Aging ; Humans ; Male ; Retrospective Studies ; Risk Factors ; Spine ; Spondylosis ; Synostosis*