CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient\'s mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians\' understanding of CAPOS syndrome, emphasizing the case\'s clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
摘要: CAPOS综合征是由ATP1A3基因引起的常染色体显性遗传的神经系统疾病，现报告1例母源性ATP1A3基因变异所致CAPOS综合征的病例，本例患儿及其母亲均表现为发热后诱发，双耳重度以上的神经性耳聋、共济失调、腱反射消失、视力下降，母亲高足弓。经全外显子测序及线粒体基因检测证实为ATP1A3c.2452G>A（Glu818Lys）杂合变异致病。本文通过阐述病例的临床特点、诊疗经过及其与基因型的相关性，提高临床医师对CAPOS综合征的认识。.

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BACKGROUND: Hand-Foot-Genital Syndrome (HFGS) is an autosomal dominant disorder characterized by a broad phenotypic spectrum. Variants in HOXA13 gene were associated with HFGS. To date, only twenty families with HFGS have been reported. However, the challenge in HFGS is the limited sample sizes and phenotypic heterogeneity. The advent of next-generation sequencing has permitted the identification of patients with HOXA13 variants who do not manifest with the full HFGS syndromic features.
METHODS: Trio (parents-proband) Whole-exome sequence(WES) and whole-genome sequencing(WGS) was carried out in this study to investigate the underlying pathogenic genetic factor of the neonate with a wide variety of clinical abnormalities.
RESULTS: No possible pathogenetic variation was detected by trio-WES, and a duplication variant in HOXA13 (c.360_377dup, p.Ala128_Ala133dup), inherited from her mother, was identified by the subsequent WGS in the proband with malnutrition, feeding difficulties, electrolyte disorders, metabolic acidosis, recurrent urinary tract infections, hydronephrosis, nephrolithiasis, abnormal ureter morphology, cholelithiasis, uterus didelphys. Sequence analysis of the variant region (exon1) indicated a high GC content of 73.92%. In addition, further enquiry of the family history revealed that 5 members of the family in 4 generations had hand and foot anomalies.
CONCLUSIONS: The neonate was diagnosed with HFGS by genetic analysis. GC content had less influence on sequence coverage in WGS than WES analysis. This was the first report of trio-WGS study for HFGS genetic diagnosis, revealed that subsequent WGS was necessary for identification of potentially pathogenic variants in unexplained genetic disorders.

In the routine treatment at the hospital, it was observed that a 31-year-old Asian woman developed foot pain after work, with clinical manifestations including local tenderness, abrasion, and a rare case of polydactyly with bilateral foot asymmetry. In addition, we also found that the patient had two-handed symmetric polydactyly. According to our observations, there seem to be few similar cases reported in the past of a two-handed symmetric polydactyly combined with a feet asymmetry polydactyly in the same person, so this is a relatively rare reported case of polydactyly. This paper aims to present detailed case report and discuss related diseases in a morphological and clinical study.

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.

Split hand/foot malformation (SHFM) is a clinically heterogeneous genetic disorder, which is mainly characterized by median clefts of the hand/feet due to the absence of the central digital rays. Several subgroups of SHFM have been identified, including SHFM1 to SHFM6. SHFM3 is an autosomal dominant disease, which has been identified to associate with a 500 kb microduplication at 10q24. The duplication involved several genes, including LBX1, BTRC, POLL, FBXW4, and so forth. In the study, using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. Further confirmation was performed using qRT-PCR assay, which showed that the 120 kb duplication was co-segregated with SHFM phenotypes in the family. It is the smallest duplication which has ever been reported relating to SHFM3. Furthermore, the transcription levels of BTRC mRNA in lymphocyte of the proband was significantly higher than that in the healthy control. The study provided evidence for the limb malformation caused by abnormal BTRC expression, and suggested that next generation sequencing could provide more precise diagnosis to SHFM3 patients.

As a clinical subtype of SWI/SNF-related intellectual disability syndromes, Nicolaides-Baraitser syndrome (NCBRS, OMIM601358) has a unique genotype-phenotype. Due to the scarcity of the number of cases reported and the limitations of diagnosis methods, so far only more than 80 cases have been reported worldwide. In this article, a new patient with a de novo mutation was followed up for 10 years; it includes the epilepsy treatment process, the characteristics of NBCRS with seizures, typical faces, sparse hair, prominent interphalangeal joints, and intellectual disability, and we also summarized the genotype-phenotype of the 80 reported cases for comparison. Due to insufficient studies and lack of attention paid to the syndrome, it is believed that the actual number of cases should be far more than the reported number. The syndrome is phased and progressive. The genotype-phenotype correlation of the disease is related to the location of the gene locus, especially closely related to the SNF2 ATPase domain. CONCLUSIONS: The understanding of NCBRS is lagging, we need to strengthen the screening process of the phenotypic disease with intellectual disability, and perfecting multiple types of diagnostic techniques will help the discovery of the disease; its clinical features are staged and are slowly progressive, and long-term prognosis must be taken precautious with long-term follow-up required.

Existed classifications of congenital proximal radioulnar synostosis (PRUS) mainly focus on osseous changes and do not cover all types of congenital PRUS, ignoring the role and developing status of the supinator. This study aims to explore the correlation between supinator development and radiographic deformity of congenital PRUS. Pediatric patients diagnosed with congenital PRUS in two pediatric Orthopedic centers were evaluated retrospectively. MRI and radiographic images of their bilateral forearms (including normal ones) were collected. The area of supinator, extensor carpi radialis longus (ECRL), extensor carpi radialis brevis (ECRB), brachioradialis (BRAR) muscle and extensor indicis (EI) muscle were measured on each forearm. The ratios of these muscles were calculated and regarded as an indicator of the developing status of supinator muscle. Twenty-seven congenital PRUS forearms of 16 patients (average 3.45 years) were included. A new MRI & X-ray classification system was proposed to cover all types of radiographic deformity and provide a comprehensive description of supinator development. This study revealed the relation between MRI measured supinator volume and radiographic deformity of congenital PRUS. Supinator muscles were observed in all congenital PRUS cases. A novel classification was proposed, providing a more comprehensive understanding of congenital PRUS.

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.

In the past, open osteotomy was always performed through a dorsal approach in the surgical treatment of brachymetatarsia, which created scar formation on the dorsal skin, subsequently resulting in dissatisfaction with cosmetic results. In this study, we provided a plantar approach to avoid forming scars on the dorsal side. A retrospective review was conducted in nine patients (13 feet) with brachymetatarsia treated with an open osteotomy and gradual bone lengthening through a plantar approach. Visual analogue scale (VAS) was used to evaluate the satisfaction of foot appearance, and we designed a questionnaire called appearance index (AI) to assess the influence of foot appearance on quality of life after surgery. The complications were also recorded during the follow-up. The patients were followed up for 34.8 ± 23.7 months. All cases were healed with a time of 64.4 ± 7.1 days and a healing index of 44.1 ± 7.8 d/cm. Satisfaction VAS for foot appearance improved from a preoperative score of 1.7 ± 1.3 points to a postoperative score of 9.3 ± 0.5 points. The AI improved from a preoperative score of 9.2 ± 0.8 points to a postoperative score of 0.6 ± 0.7 points. Complications were observed in three feet (23.1%), but none was related to the plantar approach. In conclusion, the plantar approach for metatarsal osteotomy and pins fixation was a safe and efficient technique with a satisfactory cosmetic result for the patients. No complications related to the novel approach, such as neurovascular injury, were reported.