OBJECTIVE: To evaluate the effectiveness of tibial nerve transection with epineurial suture and division of the common plantar digital nerve branches in the treatment of congenital macrodactyly in children. METHODS: A retrospective analysis was conducted on clinical data from 9 children with congenital macrodactyly who met the selection criteria and were admitted between January 2018 and December 2024. The cohort included 4 boys and 5 girls, aged 1-6 years (median, 3 years). Syndactyly of the second and third toes was present in 2 patients. Hypertrophy distribution was as follows: 1 case of single-ray involvement, 4 of double-ray, 1 of triple-ray, 1 of quadruple-ray, and 2 of quintuple-ray. Preoperatively, 7 cases exhibited limitations in both active and passive flexion and extension of the affected toes; in 2 cases, active movement was restricted while passive motion remained intact. All 9 children were unable to wear standard-sized footwear for the unaffected foot. Six presented with a limp, and 3 had difficulty walking. All 9 cases were moderate to severe progressive macrodactyly, and the growth rate of the affected foot was significantly faster than that of the healthy side. Six cases had undergone prior surgical interventions at other institutions, but disease progression continued postoperatively. All 9 patients underwent tibial nerve transection with epineurial suture and selective division of the common plantar digital nerve branches. At last follow-up, the foot growth rate was calculated (compared with that immediately after operation), and the changes of plantar pain sensation in the affected foot were detected before operation, immediately after operation, and at last follow-up, and the surgical efficacy was evaluated based on improvements in shoe fit and gait function. RESULTS: All 9 children were followed up 6-36 months, with an average of 18 months. All the incisions healed by first intention, and no infection or plantar ulceration occurred. At last follow-up, the growth rate of the affected foot was 0.10 (0.04, 0.14) cm/month, which was significantly slower than that of the healthy foot [0.14 (0.08, 0.18) cm/month] ( Z=3.951, P<0.001). Preoperatively, plantar pain sensation was absent in all cases; it was restored immediately after operation. At last follow-up, 6 patients had absent pain sensation, 2 had partial preservation (involving certain toes and central plantar regions), and 1 patient (with 3-year follow-up) exhibited regained sensation in multiple plantar areas. Gait improved in most cases, in which 8 children achieved normal ambulation, while 1 continued to limp due to leg-length discrepancy. Surgical efficacy were rated as excellent in 1 case, good in 7, and fair in 1. CONCLUSION Tibial nerve transection with epineurial suture combined with selective division of the common plantar digital nerve branches effectively reduces the growth rate of congenital macrodactyly in children, has minimal impact on plantar sensory function, and does not result in plantar ulcers or impaired ambulation.
Humans ; Male ; Female ; Child, Preschool ; Child ; Retrospective Studies ; Infant ; Tibial Nerve/surgery* ; Toes/surgery* ; Treatment Outcome ; Suture Techniques ; Fingers/surgery* ; Foot/innervation* ; Limb Deformities, Congenital

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Congenital musculoskeletal and limb deformities (CMLD) seriously affect the physical and mental health of patients, and pose great challenges to healthcare systems worldwide. We explored the specific situation and changes of incidence, prevalence, disability-adjusted life years rates, and mortality of CMLD in under-5 children from 1990 to 2021 in different groups, including different regions, periods, genders and socio-demographic indices (SDI), through corresponding analytical models. Overall, the global disease burden of CMLD in under-5 children has decreased from 1990 to 2021. The disease burden of CMLD in under-5 children varied significantly among different regions and countries, and there was a strong correlation between the corresponding burden of disease and the level of SDI. In addition, cross-country inequality analysis showed that while absolute inequalities in the disease burden of CMLD in under-5 children have improved, relative inequalities have worsened. It is essential to reduce the global health impact of CMLD by implementing targeted interventions to improve health care in underdeveloped areas.
Humans ; Global Burden of Disease/trends* ; Child, Preschool ; Global Health/statistics & numerical data* ; Infant ; Male ; Prevalence ; Limb Deformities, Congenital/mortality* ; Musculoskeletal Abnormalities/mortality* ; Female ; Disability-Adjusted Life Years ; Incidence ; Infant, Newborn ; Cost of Illness ; Socioeconomic Factors

OBJECTIVE: To explore the feasibility and early effectiveness of computer-simulated osteotomy based on the health-side combined with guide plate technique in the treatment of cubitus varus deformity in adolescents. METHODS: The clinical data of 23 patients with cubitus varus deformity who met the selection criteria between June 2019 and February 2023 were retrospectively analyzed. There were 17 males and 6 females, ranging in age from 4 to 16 years with an average of 8.5 years. The time from injury to operation was 1-4 years. The angle of distal humerus rotation was defined by humeral head posterior inclination angle using low radiation dose CT to scan the patient's upper extremity data at one time, and the preoperative rotation of the distal humerus on the affected side was (33.82±4.39)°. The CT plain scan data were imported into 9yuan3D digital orthopaedic system (V3.34 software) to reconstruct three-dimensional images of both upper extremities. The simulated operation was performed with the healthy upper extremity as the reference, the best osteotomy scheme was planned, overlapped and compared, and the osteotomy guide plate was prepared. The patients were followed up regularly after operation, and the formation of callus in the osteotomy area was observed by X-ray examination. Before and after operation, the carrying angle of both upper extremities (the angle of cubitus valgus was positive, and the angle of cubitus varus was negative) and anteversion angle were measured on X-ray and CT images. At the same time, the flexion and extension range of motion of elbow joint and the external rotation range of motion of upper extremity were measured, and Mayo score was used to evaluate the function of elbow joint. RESULTS: The operation time ranged from 34 to 46 minutes, with an average of 39 minutes. All patients were followed up 5-26 months, with a mean of 14.9 months. All the incisions healed by first intention after the operation; 2 patients had nail path irritation symptoms after Kirschner wire fixation, which improved after dressing change; no complication such as breakage and loosening of internal fixators occurred after regular X-ray review. Continuous callus formed at the osteotomy end at 4 weeks after operation, and the osteotomy end healed at 8-12 weeks after operation. At last follow-up, the carrying angle, anteversion angle, external rotation range of motion, and extension and flexion range of motion of the elbow joint of the affected side significantly improved when compared with preoperative ones ( P<0.05). Except for the extension range of motion of the healthy elbow joint ( P<0.05), there was no significant difference in other indicators between the two sides ( P>0.05). At last follow-up, the Mayo elbow score was 85-100, with an average of 99.3; 22 cases were excellent, 1 case was good, and the excellent and good rate was 100%. CONCLUSION Computer-simulated osteotomy based on health-side combined with guide plate technique for treating cubitus varus deformity in adolescents can achieve precise osteotomy, which has the advantages of short operation time and easy operation, and the short-term effectiveness is satisfactory.
Male ; Female ; Humans ; Adolescent ; Child, Preschool ; Child ; Elbow ; Humeral Fractures/surgery* ; Retrospective Studies ; Joint Deformities, Acquired/surgery* ; Elbow Joint/surgery* ; Limb Deformities, Congenital ; Osteotomy/methods* ; Humeral Head ; Range of Motion, Articular ; Computers ; Treatment Outcome

OBJECTIVE: To analyze the clinical characteristics of 170 cases of macrodactyly. METHODS: Medical records of 170 macrodactyly patients at Beijing Jishuitan Hospital between March 2006 and October 2019, including demographic characteristics, clinical presentations, anatomical distributions, X-rays, pathological findings, and treatments, were reviewed. PIK3CA mutation analyses of 12 patients were also reviewed. RESULTS: Disease incidence was similar across sex and geographical regions. Multiple-digit involvement was 3.9 times more frequent than single-digit involvement. In upper deformit: ies, the index finger, middle finger and thumb were mostly involved, and the second and third toes were the most affected on the foot. Two digits were affected more often than three digits, with the affected multiple digits were adjacent most time. The cases of progressive macrodactyly, in which the affected digits grew at a faster rate than the unaffected digits, were found more than static type. Most of progressive macrodactyly were noticed at birth. In terms of nerve involvement, affected fingers mostly occurred in the median nerve innervation area (79.4%) accompanied by median nerve and brunches enlargement and fat infiltration, i.e., nerve territory oriented; affected toes mostly occurred in the medial plantar nerve innervation area (89.1%), marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth, i.e., lipomatous. Only 17 cases had comorbid of syndactyly. The metacarpal bones were involved only in progressive type of macrodactyly. Ten of the 12 cases subjected to PIK3CA mutation analysis were positive. Among all tested specimens, PIK3CA mutation levels ranged from 7% to 27%. In terms of tissue sources in which a mutation was found, adipose tissue had the highest mutation detection rate, followed by nerve and skin. All the DNA samples of blood from the 12 PIK3CA mutation-positive patients were negative. CONCLUSION Macrodactyly fingers mostly occurred in the median nerve innervation area accompanied by median nerve and brunches enlargement and fat infiltration. The index and middle fingers were mostly involved. Macrodactyly toes mostly occurred in the medial plantar nerve innervation area, marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth. The second and third toes were the most affected on the foot. A high proportion (83%) of isolated macrodactyly patients carry activating PIK3CA mutations. Adipose, nerve, and skin tissues provide the highest PIK3CA mutation detection yield among all types of tissue studied.
DNA Mutational Analysis ; Fingers/abnormalities* ; Humans ; Infant, Newborn ; Limb Deformities, Congenital ; Mutation ; Toes

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with split hand/foot malformation (SHFM). METHODS: Genomic DNA of the proband and other affected members was extracted from peripheral blood samples. Chromosomal microarray analysis was employed to detect genome-wide copy number variations (CNVs). RESULTS: A 400 kb microduplication was identified in the 10q24.31-q24.32 region among all affected individuals. The microduplication has involved four genes, namely LBX1, BTRC, POLL and DPCD, in addition with part of FBXW4 gene. CONCLUSION The 10q24.31-q24.32 microduplication has segregated with the disease phenotype in this pedigree and probably underlay the SHFM malformation in the patients.
Asian Continental Ancestry Group ; Chromosome Duplication ; Chromosomes, Human, Pair 10 ; genetics ; DNA Copy Number Variations ; Foot Deformities, Congenital ; genetics ; Genetic Testing ; Hand Deformities, Congenital ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Pedigree

OBJECTIVE: To analyze the clinical feature of a fetus with split hand-foot malformation (SHFM) and to explore its etiology. METHODS: Ultrasonographic finding of the fetus and X-ray examination of the abortus were reviewed. Genomic copy number variations (CNVs) of the fetus was analyzed by next-generation sequencing (NGS). Its parents were subjected to chromosomal karyotyping, NGS and fluorescence in situ hybridization (FISH) assays. Real-time fluorescence quantitative PCR was used to measure the expression of genes from the region containing abnormal CNVs. RESULTS: Ultrasonography and X-ray revealed that the right hand and both feet of the fetus were in a V-shape, which was suggestive of SFHM. The results of NGS revealed that the fetus has carried a 0.36 Mb deletion at 7q21.3 region. FISH and NGS analysis of both parents were normal. Real-time fluorescence quantitative PCR confirmed that the fetus carried a single copy of DYNC1I1 gene, while the copy numbers of SEM1, DLX5 and DLX6 genes were normal. CONCLUSION The 7q21.3 microdeletion probably underlies the SHFM of the fetus, which has a de novo origin.
Chromosome Deletion ; Chromosomes, Human, Pair 7 ; genetics ; Cytoplasmic Dyneins ; genetics ; DNA Copy Number Variations ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Limb Deformities, Congenital ; genetics

OBJECTIVE: To detect pathogenic mutation of DOCK6 gene in a patient with convulsive seizure and refractory epilepsy. METHODS: CytoScan HD-Array and next generation sequencing were used to detect the potential mutation in the patient. RESULTS: The proband has carried compound heterozygous mutations of c.188C>T (p.Arg63Gln) and c.5374C>T (p.Glu1792Lys) of the DOCK6 gene, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis indicated that the two amino acids are highly conserved. Based on the ACMG guidelines, the c.188C>T mutation was predicted to be likely pathogenic, while the c.5374C>T mutation was of uncertain significance. CONCLUSION The compound heterozygous mutations of c.188C>T (p.Arg63Gln) and c.5374C>T (p.Glu1792Lys) of the DOCK6 gene probably underlie the disease in this patient.
Child ; Diabetes Mellitus, Type 2 ; Ectodermal Dysplasia ; genetics ; Guanine Nucleotide Exchange Factors ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Mutation ; Pedigree ; Scalp Dermatoses ; congenital ; genetics

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with congenital limb malformations. METHODS: Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing. RESULTS: Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members. CONCLUSION The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.
Female ; Genetic Testing ; Hand Deformities, Congenital ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Male ; Membrane Proteins ; genetics ; Pedigree ; Polydactyly ; genetics ; Thumb ; pathology