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Molecular Genetics & Genomic Medicine Jun 2024Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this...
BACKGROUND
Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly.
METHODS
Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members.
RESULTS
Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. Remarkably, the variant was absent in unaffected individuals within the pedigree, underscoring its association with the polydactyly phenotype. Computational analyses revealed that GLI3 p.Gln494His impacts a residue that is highly conserved across species.
CONCLUSION
The GLI3 zinc finger DNA-binding region is an essential part of the Sonic hedgehog signaling pathway, orchestrating crucial aspects of embryonic development through the regulation of target gene expression. This novel finding not only contributes valuable insights into the molecular pathways governing polydactyly during embryonic development but also has the potential to enhance diagnostic and screening capabilities for this condition in clinical settings.
Topics: Humans; Zinc Finger Protein Gli3; Polydactyly; Mutation, Missense; Pedigree; Male; Female; Nerve Tissue Proteins; Zinc Fingers; Kruppel-Like Transcription Factors; Fingers; Heterozygote; Southeast Asian People
PubMed: 38864382
DOI: 10.1002/mgg3.2468 -
Cureus Apr 2024Deviations from normal craniofacial development can result in a range of abnormalities, including cleft lip and/or palate, either as standalone conditions or as...
Deviations from normal craniofacial development can result in a range of abnormalities, including cleft lip and/or palate, either as standalone conditions or as components of syndromes with varying clinical characteristics. The ability to distinguish between isolated incidents and syndromes with clefts as one component is integral to achieving accurate diagnosis and therapy. The following case presentation highlights the importance of comprehensive screening and differential diagnosis in identifying syndromic connections in patients with cleft lip and palate. In this specific case, the patient presented with polydactyly, camptodactyly, and pelvic area abnormalities, indicating a possible syndromic connection with cleft lip and/or palate.
PubMed: 38779256
DOI: 10.7759/cureus.58752 -
SAGE Open Medical Case Reports 2024Polydactyly is a common congenital malformation of the hand and foot characterized by an extra digit or duplication of digits. Polydactyly can present as preaxial,...
Polydactyly is a common congenital malformation of the hand and foot characterized by an extra digit or duplication of digits. Polydactyly can present as preaxial, complex, or postaxial types. It has various presentations, and it can be an isolated anomaly or part of other diseases or syndromic conditions. Incidences are more common in European and Asian descent. The first line of treatment commonly practiced is surgery to create an aesthetically normal functioning hand. In this report, we present a case of bilateral hand polydactyly in a 2-year 6-month-old boy of Asian descent. No other abnormalities or malformations were observed elsewhere in his body. He is otherwise a healthy boy with no family history of malformations. The pattern is not consistent with any syndromic disease. He subsequently underwent surgical resection of the extra digits and a follow-up review showed normal function of the hands without contracture and other complications of the surgical site.
PubMed: 38778910
DOI: 10.1177/2050313X241255244 -
Plastic and Reconstructive Surgery.... Jan 2024Interventions for type B postaxial polydactyly include suture ligation and surgical excision, yet there is a paucity of literature comparing the outcomes of these...
BACKGROUND
Interventions for type B postaxial polydactyly include suture ligation and surgical excision, yet there is a paucity of literature comparing the outcomes of these procedures. This study sought to compare patient-reported long-term outcomes of postaxial digit excision.
METHODS
A six-question survey was distributed from January 2021 to March 2022 to patients who underwent treatment for type B postaxial polydactyly at a single pediatric institution from 2010 to 2016. Patients were queried about the incidence of pain sensitivity, keloid healing, and/or persistent presence of bump ("nubbin") at the treatment site.
RESULTS
A total of 158 responses accounting for 258 digits were attained for a 53% response rate. The majority of digits (67.4%, n = 174) were surgically excised. Median age at procedure was 49 days: 13.0 days for ligation, 63.0 days for surgical excision. Median age at survey was 8 [IQR 5.4-10.2] years. Short-term (<30 days after procedure) complications rate was 1.6%. The rate of a raised or sensitive scar was 39.5% (ligation 51.5% versus surgery 35.4%, < 0.05). The likelihood of postoperative sensitivity ( = 0.80) was similar among groups. However, the odds of a residual bump or raised scar at the surgical site was significantly higher in the ligation group ( = 0.001). These findings remained significant in the adjusted analysis.
CONCLUSION
This study suggests that suture ligation can be used in select cases without increasing the prevalence of long-term pain or sensitivity, albeit with greater risk of a bump or raised scar at the excision site compared with surgical excision.
PubMed: 38751604
DOI: 10.1097/GOX.0000000000005557 -
Cureus Apr 2024Polydactyly-myopia syndrome is a rare genetic condition characterized by the co-occurrence of polydactyly and myopia. Herein, we present the case of a 28-year-old Muslim...
Polydactyly-myopia syndrome is a rare genetic condition characterized by the co-occurrence of polydactyly and myopia. Herein, we present the case of a 28-year-old Muslim male, born of consanguineous parents, who presented with complaints of diminished vision since childhood. Ophthalmologic examination revealed severe myopia with characteristic fundus changes indicative of high myopia. Additionally, the patient exhibited polydactyly in all limbs, with a positive family history of both polydactyly and myopia. This case underscores the importance of recognizing and managing rare syndromes to provide appropriate genetic counseling and clinical care. Further research is warranted to elucidate the underlying genetic mechanisms and optimize therapeutic strategies for polydactyly-myopia syndrome. Awareness of this syndrome among healthcare providers is essential to facilitate early diagnosis and intervention for affected individuals and their families.
PubMed: 38745815
DOI: 10.7759/cureus.58235 -
European Review For Medical and... Apr 2024The study aims to provide guidance on the identification of multiple-digit malformations as potential biomarkers and therapeutic targets.
OBJECTIVE
The study aims to provide guidance on the identification of multiple-digit malformations as potential biomarkers and therapeutic targets.
MATERIALS AND METHODS
Single-cell RNA sequencing (scRNA-seq) data of four multiple-finger malformation samples were downloaded from the GEO public database. Fibroblasts and keratinocytes were divided into cellular subpopulations and the transcription factors of different subpopulations were analyzed. The regulatory network of transcription factors and their target genes were constructed to analyze the functionality of regulons.
RESULTS
Examination of the transcriptional profile data from 11,806 single cells uncovered significant associations between regulons and cell function in polydactyly. Specifically, the analysis highlighted the involvement of HOX family members and GLI2 transcription factors, including HOXD13, MSX2, LHX2, EMX2, LEF1, CREB3L2, and LHX2, in the polydactyly process within fibroblast cells. Furthermore, it sheds light on the roles of HES2 and GLIS1 in the formation and development of keratinocytes.
CONCLUSIONS
Significant presence of transcription factors, especially HOXD13, MSX2, and LHX2, may be strongly related to the development of polydactyly.
Topics: Transcription Factors; Humans; Single-Cell Analysis; Polydactyly; Gene Expression Profiling; Fibroblasts; Keratinocytes; Transcriptome; Single-Cell Gene Expression Analysis
PubMed: 38708480
DOI: 10.26355/eurrev_202404_36050 -
Annals of Medicine and Surgery (2012) May 2024Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder impacting multiple organs. Characterized by renal dysfunction, retinal dystrophy, obesity,...
INTRODUCTION AND IMPORTANCE
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder impacting multiple organs. Characterized by renal dysfunction, retinal dystrophy, obesity, polydactyly, intellectual disability, and hypogonadism, it lacks targeted treatment. Diagnosis relies on clinical criteria, and management emphasizes early detection, complication screening, and genetic counselling.
CASE PRESENTATION
A 4-year-old boy, born to first-cousin parents, presented with refractory iron-deficiency anaemia (IDA) and recurrent respiratory infections. Prenatal ultrasound revealed renal and limb anomalies. Physical examination showed dysmorphic features, polydactyly, and a giant-congenital naevus. Genetic testing revealed a homozygous MKKS variant. Despite oral iron, severe IDA persisted. Intravenous iron therapy yielded significant improvement.
CLINICAL DISCUSSION
BBS, an autosomal recessive ciliopathy, involves various genes. In this case, the MKKS gene variant contributed to the syndrome. The incidence of BBS in the Arab population is discussed, emphasizing its rarity and varied clinical presentations. Incidence in the Arab population, including Palestine, is 1 in 13 500. Diagnostic criteria, encompassing major and minor features, highlight BBS complexity. Renal anomalies, visual disturbances, and cutaneous manifestations are common. Multidisciplinary care addresses systemic involvement with emerging treatments like setmelanotide.
CONCLUSION
This case underscores BBS's rarity and complexity, featuring unique aspects like giant nevi and refractory IDA. Comprehensive management addresses renal, visual, cardiac, and neurologic aspects. Genetic counselling, prenatal testing, and preimplantation genetic diagnosis prevent transmission. Limitations include lacking local epidemiological data and prior studies in Palestine. This case contributes insights, stressing multidisciplinary management and prompting further research in underexplored populations.
PubMed: 38694397
DOI: 10.1097/MS9.0000000000001954 -
Annals of Medicine and Surgery (2012) May 2024Mirror hand is an extremely rare congenital abnormality characterized by polydactyly and duplication of the ulna, with the absence of the radius and thumb. Atypical...
INTRODUCTION
Mirror hand is an extremely rare congenital abnormality characterized by polydactyly and duplication of the ulna, with the absence of the radius and thumb. Atypical presentations of mirror hand were described, including the presence of the radius in a few cases; here the authors report one of the atypical cases of mirror hand that underwent successful management.
CASE PRESENTATION
A 2-year-old and 7-month-old female child presented with 7 well-developed digits, with an absent thumb; the X-ray imaging of the forearm showed a well-formed ulna and radius with proximal fusion. The patient has good shoulder movement, minor limitations in supination and pronation, and elbow flexion restriction. The patient underwent multiple surgical interventions for pollicization. Follow-up revealed a significant improvement of hand function and appearance.
CLINICAL DISCUSSION
In the literature review, mirror hand is a rare congenital malformation and has many varieties. The management of this deformity is a challenge and differs from case to case; here the authors described a novel variant of this deformity and its successful management.
CONCLUSION
Mirror hand is a rare congenital abnormality and has a wide spectrum of variants. The management challenge, but with early pollicization with appropriate functional considerations, the outcome is promising.
PubMed: 38694337
DOI: 10.1097/MS9.0000000000002015 -
Cureus Mar 2024Oro-facial-digital syndrome, specifically Mohr syndrome, is an uncommon genetic disorder characterized by predominant oro-facial anomalies and polysyndactyly. While...
Oro-facial-digital syndrome, specifically Mohr syndrome, is an uncommon genetic disorder characterized by predominant oro-facial anomalies and polysyndactyly. While typically associated with autosomal recessive and X-linked dominant inheritance patterns, this case presents an autosomal dominant mode of transmission. This report documents the clinical presentation of three individuals, a 12-year-old male child and two females, 10-year-old and eight-year-old, who have inherited the disorder from their ancestors. The observed features include post-axial polysyndactyly in both upper and lower limbs, with the male child exhibiting additional manifestations of strabismus and knee joint defects. Symptomatic management is pursued due to the absence of complications, with surgical interventions and subsequent cosmetic repairs planned for all three children. Post-surgical physiotherapy is scheduled as part of their comprehensive treatment plan. The prognosis for this disorder is generally favorable, with a complete recovery anticipated and no complications expected.
PubMed: 38646336
DOI: 10.7759/cureus.56623 -
International Journal of Medical... 2024Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies,...
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.
Topics: Female; Male; Humans; Bardet-Biedl Syndrome; Comorbidity; Heterozygote; Obesity; Renal Insufficiency, Chronic
PubMed: 38617006
DOI: 10.7150/ijms.92766