OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. METHODS: A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to "multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands. RESULTS: The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T>G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T>G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T>G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T>G missense mutation resulted in the failure of forming 1 disulfide bond. CONCLUSION The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.
Humans ; Pedigree ; Arthrogryposis/genetics* ; Male ; Female ; Heterozygote ; Phenotype ; Mutation ; Child ; Metalloendopeptidases

OBJECTIVE: To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face. METHODS: The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants. RESULTS: The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin. CONCLUSION The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.
Arthrogryposis ; Child ; Facies ; Female ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Mutation

OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay. METHODS: DNA was extracted from peripheral blood sample taken from the patient and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members. RESULTS: A heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene was detected in the proband, which was a verified to be de novo in origin. CONCLUSION The heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene probably underlay the disease in this child.
Arthrogryposis ; Child ; Family ; GTP-Binding Protein beta Subunits ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic etiology of two pedigrees affected with congenital arthrogryposis. METHODS: Whole exome sequencing (WES) was used to screen potential variations in the proband. Suspected variations were analyzed with bioinformatics software and validated by Sanger sequencing. RESULTS: A heterozygous c.1123G>A (p.Glu375Lys) variation was detected in the proband and an affected fetus from pedigree 1, while a de novo heterozygous c.118 G>A (p.Val40Met) variation was detected in an affected fetus from pedigree 2. CONCLUSION The two heterozygous variations of the MYH3 gene probably underlie the disease in the pedigrees. Above results have facilitated genetic counseling and prenatal diagnosis.
Arthrogryposis ; Cytoskeletal Proteins ; genetics ; Female ; Heterozygote ; Humans ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Whole Exome Sequencing

Amyoplasia is the most common form of arthrogryposis (multiple congenital contracture). It has an estimated incidence of one in 10,000 live births. Lower limb-amyoplasia is a specii c subtype with an estimated incidence of 1 in 75,000 - 100,000 live births. There are only 85 cases of lower limb amyoplasia identii ed in literature, and there are no published cases from the Philippines. We discuss a rare case of lower limb amyoplasia in an 11-year-old Filipino female presenting with additional unique features of severe scoliosis (managed with spine correction surgery) and multiple skin dimples in the gluteal area. The study was performed according to the CARE guidelines for case reports.
Arthrogryposis ; Scoliosis

Adolescent ; Adult ; Aged, 80 and over ; Arthrogryposis ; genetics ; Child ; Female ; Humans ; Male ; Middle Aged ; Pedigree

Chromosome 9p syndrome is a rare chromosomal abnormality caused by a partial deletion in chromosome 9. It was first described in 1973 by Alfi et al., and has since been shown to have diverse clinical phenotypes. Here, we reported a case of a male infant with joint contracture of the extremities, dysmorphic face, inguinal hernia, and testicular cystic masses. Chromosomal analysis revealed a terminal deletion at the short arm of chromosome 9. The major clinical features of the 9p deletion syndrome are trigonocephaly, small palpebral fissures, a flat nasal bridge, and mental retardation. To the best of our knowledge, this is the first reported case of a patient with 9p24 deletion presenting with arthrogryposis multiplex congenita.
Arm* ; Arthrogryposis* ; Chromosome Aberrations ; Chromosomes, Human, Pair 9* ; Contracture ; Craniosynostoses ; Extremities ; Hernia, Inguinal* ; Humans ; Infant ; Intellectual Disability ; Joints ; Male ; Phenotype

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B or VIPAS39 gene. The aim of this study was to investigate the clinical features and VPS33B gene mutations of an infant with ARC syndrome. A 47-day-old female infant was referred to the hospital with the complaint of jaundiced skin and sclera for 45 days and abnormal liver function for 39 days. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined diagnosis. Physical examination showed jaundice of the skin and sclera. Systemic skin was dry with desquamation in the limbs and trunk. There were no positive signs on cardiopulmonary examination. The liver was palpable 2.0 cm under the right subcostal margin. The hips and knees were flexed, and the extension was limited, with low muscular tone in the four limbs. Biochemical analysis demonstrated raised serum total bile acids, bilirubin (predominantly conjugated bilirubin) and transaminases, but the γ-glutamyl transpeptidase level was normal. Routine urine test revealed increased glucose as well as red and white blood cells. On genetic analysis, the infant was proved to be homologous for a VPS33B mutation c.1594C>T(p.R532X). She was definitely diagnosed to have ARC syndrome. Symptomatic and supportive therapy was given, but no improvement was observed, and the infant finally died at 3 months and 29 days of life.
Arthrogryposis ; blood ; genetics ; Bile Acids and Salts ; blood ; Bilirubin ; blood ; Cholestasis ; blood ; genetics ; Humans ; Mutation ; Renal Insufficiency ; blood ; genetics ; Vesicular Transport Proteins ; genetics

OBJECTIVETo delineate the clinical, electrophysiological and genetics features of a family where 4 members were affected with hereditary neuropathy with liability to pressure palsies (HNPP).

METHODSClinical features of the 4 patients were summarized. Electrophysiological examination and genetic analysis were carried out.

RESULTSAll of the patients showed recurrent motor and sensory disturbances after minor traction or constriction. Electrophysiology study revealed that the prolonged latency and reduced conduction velocity of peripheral nerve were general and with multiple sites of affection. The nerve locations liable to entrapment showed conduction block. A deletion mutation of peripheral myelin protein 22 (PMP22) gene was identified by genetic analysis.

CONCLUSIONHNPP usually affects areas where nerves are liable to entrapment, and presents with motor and sensory disturbances of the innervated areas. Electrophysiological study reveals general nervous demyelination. Genetic analysis can clarify the diagnosis of HNPP.

Adult ; Arthrogryposis ; genetics ; physiopathology ; Hereditary Sensory and Motor Neuropathy ; genetics ; physiopathology ; Humans ; Male ; Myelin Proteins ; genetics ; Neural Conduction

OBJECTIVETo investigate the correct method of bone resection and posterior capsular soft tissue releasing in total knee arthroplasty (TKA) for the patients with rheumatoid arthritis with stiff knee in flexion.

METHODSFrom November 2009 to January 2012,15 patients with rheumatoid arthritis with stiff knee in flexion underwent primary TKA and releasing of the posterior soft tissues. There were 7 males and 8 females,aged 22 to 75 years old (58.7 years old on average). The preoperative range of movement(ROM) was (3.2 ± 1.7)°. According to Knee Society score (KSS) criterion, the preoperative clinical score was 23.3 ± 12.5 and functional score was 35.2 ± 9.8. Based on the correct osteotomy, effective releasing of posterior structures was used for different degrees of flexion contracture during the TKA procedure.

RESULTSAll the patients were followed up, and the average duration was 2.3 years (1.6 to 3 years). At the latest follow-up,the KSS clinical score was 81.7 ± 6.5 and functional score was 82.8 ± 9.3. The flexion and extension ROM of the knee joint was (103.5 ± 13.1). Three knees remained 50 flexion contracture deformity, but the function of the affect knees was good.

CONCLUSIONThe effective releasing of the soft tissue of posterior capsule is a major management for correction of the flexion contracture in TKA. The correct releasing of posterior structure can not only achieve fundamental gap of TKA but also effectively avoid bone over-resection.

Adult ; Aged ; Arthritis, Rheumatoid ; complications ; physiopathology ; surgery ; Arthrogryposis ; surgery ; Arthroplasty, Replacement, Knee ; methods ; Female ; Humans ; Joint Capsule Release ; methods ; Male ; Middle Aged ; Range of Motion, Articular