Search Results (42)

Fanconi anemia (FA) is a rare inherited disorder characterized by genomic instability, congenital anomalies, and progressive bone marrow failure; such manifestations may vary across populations, partly due to differences in genetic background. This study aims to describe the clinical and molecular spectrum of FA in Mexican patients. A total of 14 patients with clinical suspicion of FA were evaluated; cytogenetic and molecular analyses were successfully performed using MLPA and NGS. Clinically, short stature was present in 100% (n = 14) of the patients, followed by upper limb abnormalities, which were present in 78.6% (n = 11) of the patients, and microphthalmia, which was present in 71.4% (n = 10) of the patients. Molecular analysis identified pathogenic variants in FANCA (78.6%, n = 11), FANCC (14.3%, n = 2), and FANCE (7.1%, n = 1), with a relatively balanced distribution of homozygous (57.1%, n = 8) and compound heterozygous variants (42.9%, n = 6). Notably, the FANCA:c.3931_3932del variant was recurrent in six patients from the same geographic region (Michoacan), suggesting possible regional enrichment. Our findings expand the clinical and molecular characterization of FA in Mexican patients and underscore the importance of integrating phenotypic and genomic data to better understand population-specific patterns of this disorder. Full article

Lbx1 plays important roles in different processes, including the development of sensory pathways, neuronal cell fate regulation, and muscle cell precursor migration. Genetic variation in the LBX1 locus has been associated with several human disease conditions, such as idiopathic scoliosis, congenital limb malformation, and neuropsychiatric illness, including attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders. Zebrafish (Danio rerio) were used to investigate the behavioral consequences of the loss of function of the two orthologs to the human LBX1 gene, zebrafish lbx1a and lbx1b. We observed a consistent locomotor hyperactivity phenotype induced by a novel environment in lbx1a mutants. Repeated dark stimuli provoked similar responses in both mutant lines, including the novelty-induced hyperactivity. We performed RNAseq on total RNA isolated from the head region of mutant and wildtype larvae. Several differentially expressed genes were identified, giving more insights into Lbx1 target genes and pathways, which could be relevant regarding the evaluation of zebrafish lbx1a or lbx1b as a human disease model. Furthermore, the analysis was complemented with a comparison to the expression profile of human LBX1 overexpression in cell culture, revealing a convergence on just two commonly regulated genes, namely alpha-Internexin (INA) and Fibrillin-3 (FBN3). In conclusion, our findings might further elucidate the multitude of functions of Lbx1 and its involvement in various human disease conditions. Full article

Flexural deformities (FDs) are a common condition in foals. Therapy is typically initiated without a precise diagnosis, and the etiopathogenesis often remains unknown. This study aimed (1) to investigate the clinical and pathological findings in congenital FD cases in foals and (2) to retrospectively describe the abnormalities detected in muscle biopsies of foals affected by CFDs. For these purposes, a retrospective study of the findings of muscle biopsies taken from foals with FDs referred to the Department of Veterinary Medicine and Animal Production at the University of Naples Federico II was performed from January 2005 to February 2024. Anamnesis, physical examination, hematological and biochemical data, along with the findings of histopathological muscle biopsy analysis and follow-up, were recorded. The clinical records of 15 cases of FDs were evaluated. The main clinical symptoms included flexural limb deformities associated with weakness, torticollis and scoliosis, mandibular prognathism, and inferior eyelid entropion. The evaluation of histopathological reports allowed us to observe the following muscle disorders: Core-like myopathy, mild nonspecific myopathy, mitochondrial myopathy, congenital fiber type disproportion, lipid storage myopathy, lipomatous dystrophy, myopathy with inclusion bodies, polysaccharide storage myopathy, and neurogenic myopathy. Even though many cases of FDs were diagnosed through clinical examination and successfully treated, we hypothesize that different underlying etiologies may present with similar flexural symptoms. A better understanding of these underlying causes is, therefore, desirable. These findings suggest that histopathological analysis may be a valuable tool for investigating FDs in foals, although further studies are needed to evaluate the significance of the observed alterations. Full article

Background and Clinical Significance: Proximal femoral focal deficiency (PFFD), also referred to as congenital femoral deficiency, is a longitudinal limb deficiency and birth defect that affects the lower extremity including the hip and femur, resulting in a deformed and shortened limb. It can be diagnosed and classified using a combination of imaging modalities, including radiographs, ultrasonography, magnetic resonance imaging and computerized tomography. It is crucial to characterize this birth defect in the prenatal period to appropriately prepare parents through counseling. Postnatal imaging should be performed to confirm the diagnosis, prognosticate and predict the patient’s course for treatment and management. Close follow-up and family/patient-centered care contribute to optimized patient outcomes. Case Presentation: Here, we present a series of three cases of varying PFFD severity and presentation, detailing the evaluation process, the limitations and value of imaging, and the treatment outcomes of these patients. Each case has a different PFFD classification and treatment strategy that we utilized according to the data that we attained through continuous patient care and discussion. Conclusions: We highlight the difficulties in identifying and classifying PFFD in the prenatal period while demonstrating how postnatal imaging clarified the diagnosis and informed appropriate counseling and treatment. Close follow-up and the length of patient continuity allowed us to maximize patient outcomes despite the variety in PFFD presentation and severity. Full article

A limp is an abnormal, uneven or laboured gait typically resulting from pain, weakness, or structural deformity involving the hip, lower limb, spine or abdominopelvic abnormalities. Limps in children are common and have diverse causes that can be benign to life-threatening including trauma, congenital malformations, and neoplastic diseases. Diagnosis involves identifying gait abnormality thoroughly examining history and physical exam, assessing tenderness and range of motion, and completing targeted lab and radiographic studies. We present an imaging review of various usual and unusual causes of limp in different age groups such as in toddlers (1–3 years), children (4–10 years), and adolescents (11–16 years) with a comprehensive literature review. Full article

Background: Limb deformity describes a condition where a limb has an abnormal shape or length, resulting from an acquired or a congenital case. This condition can impair the normal function of patients’ lives, leading to adverse psychological impacts. The limb deformity-modified Scoliosis Research Society (LD-SRS) score is a frequently used tool to assess quality of life. This observational study aimed to investigate the quality of life of patients with debilitating limb deformities in Saudi Arabia using the LD-SRS score. Methods: This is an observational analytical cross-sectional study conducted at the orthopedic clinic at King Saud University Medical City between March and May 2024. Patients diagnosed with any type of limb deformity (of different ages) were included in this study. Patients completed the LD-SRS score in the clinic and were divided into two groups based on whether they had undergone surgery for limb deformity. Results: This study included 152 participants, with the majority of participants in the 13–18-year age group and predominantly male (59.87%). Most participants were assessed before treatment, with significant differences observed in total scores based on the examination time (p < 0.001). Post-surgery scores showed marked improvement, with the overall total mean score for the surgery group being significantly higher than that of the non-surgery group (p < 0.001). Domain-specific scores revealed higher satisfaction in self-image/appearance for the surgery group, while the non-surgery group had lower scores in function/activity and mental health domains. No significant differences were found across age, gender, side of the body affected, or affected site. Conclusions: Preoperative patients had lower QoL scores as a whole group compared to those who had undergone surgery. The longer the duration postoperatively, the better the QoL score; those measured at three months had better QoL than preoperative patients, and those assessed at one and two years scored even higher. Self-image/appearance was a key factor, with the surgery group scoring higher in this domain than the non-surgery group. Future research should explore broader patient perspectives, including those related to mental and social well-being. Full article

Background: Pose estimation (PE) has the promise to measure pediatric movement from a video recording. The purpose of this study was to quantify the accuracy of a PE model to detect arm and leg movements in 3-month-old infants with and without (TD, for typical development) complex congenital heart disease (CCHD). Methods: Data from 12 3-month-old infants (N = 6 TD and N = 6 CCHD) were used to assess MediaPipe’s full-body model. Positive predictive value (PPV) and sensitivity assessed the model’s accuracy with behavioral coding. Results: Overall, 499 leg and arm movements were identified, and the model had a PPV of 85% and a sensitivity of 94%. The model’s PPV in TD was 84% and the sensitivity was 93%. The model’s PPV in CCHD was 87% and the sensitivity was 98%. Movements per hour ranged from 399 to 4211 for legs and 236 to 3767 for arms for all participants, similar ranges to the literature on wearables. No group differences were detected. Conclusions: There is a strong promise for PE and models to describe infant movements with accessible and affordable resources—like a cell phone and curated video repositories. These models can be used to further improve developmental assessments of limb function, movement, and changes over time. Full article

Background: Normative data on hand and precision grip strengths are essential for evaluating the level of development, the efficacy of rehabilitation, and treatment results. The need for established norms of grip strength in Polish children is one of the problems that Polish physiotherapists and physicians face when treating upper limbs. The aim was to establish normative values of hand and precision grips strengths in Polish children and adolescents aged 3–19. Methods: In the years 2012–2023, a sample of 358 children and adolescents with no history of upper limb injuries or congenital upper extremity defects were randomly chosen from kindergartens, primary schools, middle schools, and high schools. They were living in urban agglomerations and in smaller towns or villages. Hand and precision grips like the pincer, three-point, side, and opposition grip strength were assessed using a hand dynamometer and pinchmeter in standard positions. Results: The strength in all types of examined hand grips increases with chronological age in both genders. The grip strength was higher in the boys’ group than in the girls’ and it was higher in the right hand than in the left, but the difference was no more greater than 10%. Detailed data with standard deviation were presented in the form of a table, divided by age and sex. Conclusions: Norms for grip strength were provided for Polish children and adolescents aged 3–19, allowing therapists and physicians to compare Polish patients with that of normally developed, healthy children of the same age and sex. Full article

Congenital or acquired hand differences, including unilateral below-elbow deficiencies, present complex challenges in pediatric rehabilitation. Surgical management and prosthetic provision represent a big challenge to find a good balance for guaranteeing optimal hand function. There is no specific assessment tool for measuring these aspects in the Italian context. The present study investigates the psychometric properties of the ABILHAND-Kids in children with congenital unilateral below-elbow deficiencies and acquired amputation of the upper limb. We measure internal consistency using Cronbach coefficient alpha and the intraclass correlation coefficient (ICC) for measuring test-retest reliability. Differences in hand function in both children with acquired or congenital diseases were also investigated. Participants to the study were 107 (49 F and 58 M) children, with a mean (SD) age of 8.88 (4.25). For test retest reliability, conducted on a sub-sample of 58 children, the ICC was 0.92, while for internal consistency, the Cronbach coefficient alpha was 0.90. We did not find statistically significant differences in scoring (p = 0.33) in the use (mean 29.25 SD 6.58) or non-use of a prosthetic device (mean 30.74 SD 7.43), while statistically significant differences were found in hand function (p < 0.01) for children who had a congenital impairment (mean 31.87 SD 6.49) and children who had an acquired amputation (mean 27.77 SD 6.60). In conclusion, the ABILHAND-Kids showed good internal consistency and reliability and can capture differences in hand function in children with both congenital and acquired hand disorders. Full article

The American crocodile (Crocodylus acutus, Cuvier, 1807) (Class Reptilia, Family Crocodylidae) is a crocodile species inhabiting the Neotropics. Congenital defects have been described in almost every vertebrate group. In crocodiles, teratology alterations have been described in captive animals (pets, zoos, farms) such as Crocodylus niloticus or Gavialis gangeticus. The present study aimed to characterize congenital malformations of C. acutus from a farm in Lomas de Matunilla, Ballestas, Bolívar, Colombia. A total of 550 unhatched eggs were examined after embryo death. A total of 61 embryos presented malformations, with 42 different types of anomalies observed. Limb and tail malformations (29%) were the most common malformations observed. Several malformations, such as cephalothoracopagus, thoracopagus, sternopagus, xiphopagus twins, campylorrachis scoliosa, and acrania, were documented in crocodiles for the first time. Research in teratology enhances our understanding of crocodile biology. It plays a role in their conservation and management, thus helping to ensure the long-term viability of these species in their natural habitats. Full article

An 8-month-old, 3.4 kg, castrated male Toy Poodle was referred for progressive tetraparesis and respiratory disorder without a history of trauma. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) with different positions of the neck revealed concurrent atlanto-occipital dislocation (AOD) and atlantoaxial instability (AAI) with spinal cord compression. This case was unique due to its congenital nature and the absence of trauma. The surgical treatment involved precise removal of the C1 vertebra’s ventral articular facet, which was compressing on the spinal cord, attributed to its fixed and malaligned position within the atlantooccipital joint. Following facetectomy, the stabilization of the occipital bone to the C2 vertebra was achieved by screws, wire, and polymethyl methacrylate. Two days after surgery, the dog recovered ambulation and showed gradual improvement in gait, despite mild residual ataxia. Postoperative CT and radiographs showed successful decompression of the spinal cord. The screw loosening was confirmed at 114 days, which was managed successfully by extracting the affected screws. Through the 21-month monitoring period, the dog showed a normal gait with a wide-based stance of the pelvic limbs when standing and experienced no pain. This case represents the first report of concurrent congenital AOD and AAI treated with a ventral surgical approach, contributing new insights to the understanding and management of such complex cranio-cervical junction disorders in veterinary neurosurgery. Full article

Macrodactyly is a rare congenital limb difference manifesting as an overgrowth of one or more fingers or toes. The pathological process affects all tissues of the ray in the hand or foot. The enlargement can significantly alter the limb’s appearance and impair its function. The role of a pediatrician is to distinguish isolated macrodactyly from syndromic conditions (including PIK3CA-Related Overgrowth Spectrum) or mimicking conditions to enable early interdisciplinary consultation and treatment planning. The psychological stigma associated with this often disfiguring condition necessitates support for patients and their family. We present a practical guide for physicians who might be the first to raise suspicion of macrodactyly and initiate further diagnostics to achieve adequate treatment and support for children and caregivers. Full article

Pathogenetic mechanism recognition and proof-of-concept clinical trials were performed in our patients affected by collagen VI-related myopathies. This study, which included 69 patients, aimed to identify innovative clinical data to better design future trials. Among the patients, 33 had Bethlem myopathy (BM), 24 had Ullrich congenital muscular dystrophy (UCMD), 7 had an intermediate phenotype (INTM), and five had myosclerosis myopathy (MM). We obtained data on muscle strength, the degree of contracture, immunofluorescence, and genetics. In our BM group, only one third had a knee extension strength greater than 50% of the predicted value, while only one in ten showed similar retention of elbow flexion. These findings should be considered when recruiting BM patients for future trials. All the MM patients had axial and limb contractures that limited both the flexion and extension ranges of motion, and a limitation in mouth opening. The immunofluorescence analysis of collagen VI in 55 biopsies from 37 patients confirmed the correlation between collagen VI defects and the severity of the clinical phenotype. However, biopsies from the same patient or from patients with the same mutation taken at different times showed a progressive increase in protein expression with age. The new finding of the time-dependent modulation of collagen VI expression should be considered in genetic correction trials. Full article

Maternal smoking during pregnancy has been associated with adverse effects on foetal development, including congenital limb anomalies. This systematic review aimed to provide an updated assessment of the association between maternal smoking during pregnancy and the risk of congenital limb anomalies. A systematic search was conducted to identify relevant studies published up to February 2023. Studies reporting on the relationship between maternal smoking during pregnancy and congenital digital anomalies or congenital limb reduction defects were included. Two independent reviewers screened the studies, extracted data, and assessed the quality of the included studies. Meta-analyses were performed to estimate the pooled odds ratios with 95% confidence intervals using fixed and random-effects models. In total, 37 publications comprising 11 cohort and 26 case-control studies were included in the systematic review. The meta-analysis demonstrated a significant increased risk of congenital limb reduction defects (pooled OR: 1.27, 95% CI: 1.18–1.38) in infants born to mothers who smoked during pregnancy. Similarly, a significant relationship was observed for the development of polydactyly/syndactyly/adactyly when considered as a single group (pooled OR: 1.32, 95% CI: 1.25–1.40). Yet, in contrast, no significant association was observed when polydactyly (pooled OR: 1.06, 95% CI: 0.88–1.27) or syndactyly (pooled OR: 0.91, 95% CI: 0.77–1.08) were considered individually. This systematic review provides updated evidence of a significant relationship between maternal smoking during pregnancy and increased risk of congenital limb anomalies. These findings highlight the potential detrimental effects of smoking on foetal limb development and underscore the importance of smoking cessation interventions for pregnant women to mitigate these risks. Full article

Lymphangioma is a congenital anomaly in which abnormal lymphatic drainages localize to form a benign mass, but it has the tendency to grow in size and the potential to infiltrate surrounding structures, causing devastating effects and leading to severe morbidity. The most common site of lymphangioma is the neck region (cystic hygroma colli), whereas lymphangioma in the lower limbs is very rare, accounting for only 2% of cases. Accordingly, the prenatal diagnosis of lymphangioma of the lower limbs has been scarcely reported. This study describes two cases of lymphangioma of the lower limbs, focusing on unique sonographic features and the natural course of rapidly progressive changes, which is different from nuchal lymphangioma. Based on previous isolated case reports together with our two cases, lymphangioma of the lower limbs usually develops in the second trimester, tends to have rapidly progressive changes, and is unlikely to be associated with aneuploidy and structural anomalies. Diagnoses can be made by using sonographic findings pertaining to the subcutaneous complex and multi-septate anechoic cystic lesions in the lower limbs, the latter of which can infiltrate visceral structures. Prenatal detection can be helpful in laying the groundwork for providing counseling to the parents and the planning of management strategies, i.e., opting to terminate the pregnancy, revising delivery plans, and looking towards the postnatal management of the infant. Full article