-
The Journal of Pediatrics Aug 2023To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on...
OBJECTIVE
To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with cancer and congenital abnormalities.
STUDY DESIGN
Tumeur Et Développement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking.
RESULTS
From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm.
CONCLUSIONS
In the first Tumeur Et Développement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.
Topics: Child; Humans; Cohort Studies; Intellectual Disability; Prospective Studies; Biological Specimen Banks; Central Nervous System Neoplasms; Congenital Abnormalities
PubMed: 37169337
DOI: 10.1016/j.jpeds.2023.113451 -
Pediatric Annals Apr 2024Metatarsus adductus (MA), the most common congenital foot deformity, involves adduction of the forefoot at the tarsometatarsal joint, with normal hindfoot alignment.... (Review)
Review
Metatarsus adductus (MA), the most common congenital foot deformity, involves adduction of the forefoot at the tarsometatarsal joint, with normal hindfoot alignment. Early diagnosis is important because treatment is more successful if initiated before age 9 months. Treatment of MA depends on deformity severity, in which mild to moderate deformity can be treated conservatively. Current standard of care for severe or rigid deformity involves referral by primary care physicians to specialists for management by casting and splinting. Recently, several orthoses have demonstrated equal effectiveness to casting and may allow for primary care physicians to treat MA without the need for referral. In this review article, we provide an overview of MA and discuss diagnosis and treatment. We also discuss novel devices and suggest how they may affect the future management of severe and rigid MA. .
Topics: Humans; Foot Deformities, Congenital; Metatarsus Varus
PubMed: 38574072
DOI: 10.3928/19382359-20240206-02 -
European Journal of Human Genetics :... Nov 2023Polydactyly is the most common limb malformation that occurs in 1.6-10.6 per one thousand live births, with incidence varying with ancestry. The underlying gene has been...
Polydactyly is the most common limb malformation that occurs in 1.6-10.6 per one thousand live births, with incidence varying with ancestry. The underlying gene has been identified for many of the ~100 syndromes that include polydactyly. While for the more common form, nonsydromic polydactyly, eleven candidate genes have been reported. We investigated the underlying genetic cause of autosomal recessive nonsyndromic postaxial polydactyly in four consanguineous Pakistani families. Some family members with postaxial polydactyly also present with syndactyly, camptodactyly, or clinodactyly. Analysis of the exome sequence data revealed two novel homozygous frameshift deletions in EFCAB7: [c.830delG;p.(Gly277Valfs*5)]; in three families and [c.1350_1351delGA;p.(Asn451Phefs*2)] in one family. Sanger sequencing confirmed that these variants segregated with postaxial polydactyly, i.e., family members with postaxial polydactyly were found to be homozygous while unaffected members were heterozygous or wild type. EFCAB7 displays expressions in the skeletal muscle and on the cellular level in cilia. IQCE-EFCAB7 and EVC-EVC2 are part of the heterotetramer EvC complex, which is a positive regulator of the Hedgehog (Hh) pathway, that plays a key role in limb formation. Depletion of either EFCAB7 or IQCE inhibits induction of Gli1, a direct Hh target gene. Variants in IQCE and GLI1 have been shown to cause nonsyndromic postaxial polydactyly, while variants in EVC and EVC2 underlie Ellis van Creveld and Weyers syndromes, which include postaxial polydactyly as a phenotype. This is the first report of the involvement of EFCAB7 in human disease etiology.
Topics: Humans; Hedgehog Proteins; Zinc Finger Protein GLI1; Polydactyly; Fingers; Limb Deformities, Congenital
PubMed: 37684519
DOI: 10.1038/s41431-023-01450-5 -
Advances in Neonatal Care : Official... Feb 2024Assessment of the foot is an essential part of the newborn examination. Foot abnormalities range from an isolated deformity due to intrauterine positioning to a... (Review)
Review
BACKGROUND
Assessment of the foot is an essential part of the newborn examination. Foot abnormalities range from an isolated deformity due to intrauterine positioning to a functional impairment due to a structural malformation. The purpose of this article is to review assessment, abnormal findings, and current treatment options of common foot deformities.
EVIDENCE ACQUISITION
A review of literature was conducted using keywords in PubMed, Google Scholar, and CINAHL databases from 2018 to 2023.
RESULTS
Although assessment techniques for the neonatal foot remain the same, recent nonsurgical treatment options are available for a variety of neonatal foot deformities. Early recognition allows for proper evaluation of foot deformities and corrective measures.
IMPLICATIONS FOR PRACTICE AND RESEARCH
Neonatal providers equipped with knowledge of common foot problems can provide support and anticipatory guidance to families.
Topics: Infant, Newborn; Humans; Foot Deformities; Foot Deformities, Congenital
PubMed: 38113895
DOI: 10.1097/ANC.0000000000001116 -
Dental Clinics of North America Apr 2024This review aims to present a detailed analysis of the most common developmental and acquired dental abnormalities, including caries, resorptive lesions, and congenital... (Review)
Review
This review aims to present a detailed analysis of the most common developmental and acquired dental abnormalities, including caries, resorptive lesions, and congenital anomalies of teeth number, size, form, and structure. This review highlights how diagnostic imaging can aid in the accurate identification and management of these conditions.
Topics: Humans; Dental Caries; Tooth Abnormalities
PubMed: 38417988
DOI: 10.1016/j.cden.2023.09.001 -
European Spine Journal : Official... Nov 2023The main objective of this study was to assess the overall incidence of genitourinary anomalies in patients with congenital scoliosis by providing the highest level of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The main objective of this study was to assess the overall incidence of genitourinary anomalies in patients with congenital scoliosis by providing the highest level of evidence. The secondary objective was to look for associations and trends influencing the incidence.
METHODS
A meta-analysis using PubMed, Embase, Scopus, and the Cochrane Collaboration Library database was carried out. We included studies focusing on patients with congenital scoliosis and genitourinary anomalies. The main outcome was the incidence of genitourinary anomalies in congenital scoliosis. We also collected the following data: patient gender, type of deformity (formation, segmentation, or mixed), deformity location, and associated anomalies. We included cohort studies. Data was extracted from published reports and combined using Review Manager 5.4. The quality of the included studies was assessed independently by two authors using the Methodological Index for Non-Randomized Studies (MINORS) criteria.
RESULTS
A total of eight cohort studies were included from a pool of 2781 patients. The incidence of genitourinary anomalies associated with congenital scoliosis was 22.91% (95% CI 13.39-32.43%). The incidence of surgically treated genitourinary anomalies was 13.92% (95% CI 4.54-23.31%). There were no differences related to gender (male 49.3% versus female 50.7%; p > 0.05). There were no differences regarding the type of deformity. The incidences of associated intraspinal, cardiac, musculoskeletal and craniofacial anomalies were 33.30%, 17.60%, 27.77% and 19.83% respectively. The most frequent genitourinary anomalies were: unilateral kidney (111/388); renal ectopia (50/367); obstructive uropathy (30/201), horseshoe kidney (30/313) and undescended testicle (16/180).
CONCLUSIONS
The incidence of genitourinary anomalies associated with congenital scoliosis was 22.91%, and 13.92% were surgically treated. Unilateral kidney was the most common genitourinary abnormality. There were no differences between genders and deformity types. It is important to consider the association between genitourinary anomalies and intraspinal or musculoskeletal anomalies.
Topics: Humans; Male; Female; Scoliosis; Incidence; Retrospective Studies; Cohort Studies; Urogenital Abnormalities
PubMed: 37572143
DOI: 10.1007/s00586-023-07889-w -
Human Molecular Genetics Sep 2023Human vertebral malformations (VMs) have an estimated incidence of 1/2000 and are associated with significant health problems including congenital scoliosis (CS) and...
Human vertebral malformations (VMs) have an estimated incidence of 1/2000 and are associated with significant health problems including congenital scoliosis (CS) and recurrent organ system malformation syndromes such as VACTERL (vertebral anomalies; anal abnormalities; cardiac abnormalities; tracheo-esophageal fistula; renal anomalies; limb anomalies). The genetic cause for the vast majority of VMs are unknown. In a CS/VM patient cohort, three COL11A2 variants (R130W, R1407L and R1413H) were identified in two patients with cervical VM. A third patient with a T9 hemivertebra and the R130W variant was identified from a separate study. These substitutions are predicted to be damaging to protein function, and R130 and R1407 residues are conserved in zebrafish Col11a2. To determine the role for COL11A2 in vertebral development, CRISPR/Cas9 was used to create a nonsense mutation (col11a2L642*) as well as a full gene locus deletion (col11a2del) in zebrafish. Both col11a2L642*/L642* and col11a2del/del mutant zebrafish exhibit vertebral fusions in the caudal spine, which form due to mineralization across intervertebral segments. To determine the functional consequence of VM-associated variants, we assayed their ability to suppress col11a2del VM phenotypes following transgenic expression within the developing spine. While wildtype col11a2 expression suppresses fusions in col11a2del/+ and col11a2del/del backgrounds, patient missense variant-bearing col11a2 failed to rescue the loss-of-function phenotype in these animals. These results highlight an essential role for COL11A2 in vertebral development and support a pathogenic role for two missense variants in CS.
Topics: Animals; Humans; Scoliosis; Zebrafish; Spine; Abnormalities, Multiple; Mutation, Missense; Collagen Type XI
PubMed: 37462524
DOI: 10.1093/hmg/ddad117 -
Child's Nervous System : ChNS :... Jun 2024Sacral agenesis (SA) includes a range of clinical presentations of varying severity, with implications for function and quality of life (QoL). Diagnosis is often made...
INTRODUCTION
Sacral agenesis (SA) includes a range of clinical presentations of varying severity, with implications for function and quality of life (QoL). Diagnosis is often made perinatally, and prognostic discussions become an important aspect of parental counselling. This study engaged SA sufferers and their caregivers to obtain objective, long-term patient reported outcome data.
METHOD
Patients with radiologically confirmed SA from a single tertiary spinal unit underwent retrospective medical record review. Patients were then contacted by telephone to complete QoL questionnaires including EQ-ED-5L for adults and EQ-ED-Y for < 16-year-olds. Additional information including Renshaw grade, employment, living situation and bladder function was also collected.
RESULTS
Twenty-six patients with SA were identified. Mean age is 23.35 years (range 0.92-63.53), 13 M:17F. Renshaw grade ranged from 1 to 4. Sixty-eight percent had associated kyphoscoliotic deformities. The majority (70%) had either impaired or absent bladder control, and 80% need walking aids to mobilise. Twenty patients completed the questionnaire (10 adults and 10 < 16-year-olds). Mean EQ-ED-5L index for adults was +0.474 (range -0.1 to +0.089, 1 = best), with a lower mean value of +0.287 (range -0.54 to +1) for the < 16-year cohort. Those undergoing spinal fusion procedures had significantly lower scores (-0.08 v +0.44, p = 0.022).
CONCLUSION
This study provides an objective record of the QoL of individuals with SA, illustrating a wide variety of outcomes, with differences between younger and older individuals which may reflect the results of a long-term adaptive process. The implications for individuals should be carefully tailored to the specific deformity and the likely underlying neurological deficits.
Topics: Humans; Female; Male; Adolescent; Adult; Young Adult; Child; Quality of Life; Child, Preschool; Middle Aged; Retrospective Studies; Infant; Sacrum; Surveys and Questionnaires; Treatment Outcome; Abnormalities, Multiple; Meningocele; Sacrococcygeal Region
PubMed: 38411707
DOI: 10.1007/s00381-024-06326-7 -
The Journal of Hand Surgery, European... Dec 2023Ulnar dimelia is a very rare unilateral congenital upper limb anomaly (CULA) affecting the whole extremity. Treatment remains difficult because of the complexity and... (Review)
Review
Ulnar dimelia is a very rare unilateral congenital upper limb anomaly (CULA) affecting the whole extremity. Treatment remains difficult because of the complexity and multi-level involvement. Twenty-four cases with duplicated ulna, absent radius and polydactyly from seven European centres were reviewed according to a structured list of parameters. At first consultation, median age 8 months (1-178), the shoulder movement was good in 17 patients or poor in six, and the median passive elbow range of motion was 20° (0°-90°). The resting wrist position was flexed in 22/24 patients. Following stretching and splinting, elbow surgery included resection of the lateral proximal ulna in 11 patients and muscle transfers in six to improve passive movement and increase active elbow motion, respectively. Tendon transfers were performed in eight wrists and a pollicization or pseudo-pollicization in 23 patients. Overall, patients demonstrate acceptable function postoperatively. Guidelines for treatment of this severe CULA are presented. IV.
Topics: Humans; Hand Deformities, Congenital; Ulna; Polydactyly; Wrist Joint; Upper Extremity; Radius
PubMed: 37684016
DOI: 10.1177/17531934231196418 -
Journal of Minimally Invasive Gynecology Sep 2023To investigate the possibility of conservative management of rudimentary uterine horns associated with vaginal agenesis. (Observational Study)
Observational Study
STUDY OBJECTIVE
To investigate the possibility of conservative management of rudimentary uterine horns associated with vaginal agenesis.
DESIGN
Observational study on cohort of consecutive cases treated with the same criteria from 2008 to 2021.
SETTING
Two academic institutions and teaching hospitals in Milan, Italy.
PATIENTS
Eight patients with vaginal agenesis associated with rudimentary cavitated uterine horns treated by the same team and postoperatively followed.
INTERVENTIONS
All the subjects underwent the same standardized surgical procedure: laparoscopy, intraoperative ultrasound, and horn-vestibular direct anastomosis. Postoperatively vaginoscopy was performed every 6 months.
MEASUREMENTS AND MAIN RESULTS
The postoperative course was generally uneventful and the mean hospital stay was 4.3 ± 2.5 (SD) days. All the patients began to menstruate a few months after the operation. Menstrual flows were light but regular. All patients had a neovaginal length > 4 cm at 1 year postoperatively, reaching approximately 6 cm at 2 years. During the follow-up period, 5 patients were sexually active without dyspareunia. In all cases, surgery restored the continuity of the neovagina and uterine horn through the creation of a "vaginal-horn fistula tract."
CONCLUSION
In patients with vaginal agenesis associated with the presence of a uterine cavitary horn, it is possible to recover not only sexual activity but also menstrual function. The horn-vestibular anastomosis may be considered a valid, safe, and effective therapeutic option but requires accurate preoperative and intraoperative evaluation of rudimentary uterine structures.
Topics: Female; Humans; Abnormalities, Multiple; Congenital Abnormalities; Laparoscopy; Mullerian Ducts; Plastic Surgery Procedures; Uterus; Vagina; Vaginal Fistula
PubMed: 37172890
DOI: 10.1016/j.jmig.2023.05.002