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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 -
European Journal of Human Genetics :... May 2024Orofaciodigital syndrome is a distinctive subtype of skeletal ciliopathies. Disease-causing variants in the genes encoding the CPLANE complex result in a wide variety of...
Orofaciodigital syndrome is a distinctive subtype of skeletal ciliopathies. Disease-causing variants in the genes encoding the CPLANE complex result in a wide variety of skeletal dysplasia with disturbed ciliary functions. The phenotypic spectrum includes orofaciodigital syndrome and short rib polydactyly syndrome. FUZ, as a part of the CPLANE complex, is involved in intraflagellar vesicular trafficking within primary cilia. Previously, the variants, c.98_111+9del and c.851G>T in FUZ were identified in two individuals with a skeletal ciliopathy, manifesting digital anomalies (polydactyly, syndactyly), orofacial cleft, short ribs and cardiac defects. Here, we present two novel variants, c.601G>A and c.625_636del in biallelic state, in two additional subjects exhibiting phenotypic overlap with the previously reported cases. Our findings underscore the association between biallelic loss of function variants in FUZ and skeletal ciliopathy akin to orofaciodigital syndrome.
PubMed: 38702430
DOI: 10.1038/s41431-024-01619-6 -
DNA and Cell Biology May 2024Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain...
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of but also enhances our understanding of the mechanisms connecting with overgrowth syndromes.
PubMed: 38700464
DOI: 10.1089/dna.2023.0391 -
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 -
Special Care in Dentistry : Official... May 2024The VACTERL association or Syndrome consists of Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, and Limb defects. The diagnosis relies on the presence of at...
AIM
The VACTERL association or Syndrome consists of Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, and Limb defects. The diagnosis relies on the presence of at least three of these structural abnormalities. This study reports a single case of a patient with VACTERL Syndrome (VS), aiming to assist dentists in recognizing the general aspects, systemic changes, and oral care related to this condition.
CASE REPORT
A 14-year-old female patient medically diagnosed with VS. The study evaluated the presence of systemic alterations, medication use, behavioral deviations, cognitive development, and oral aspects. The patient exhibited cardiovascular alterations including a ventricular septal defect (C), anal atresia (A), polydactyly (considered limb alteration-L), and scoliosis (a possible indication of vertebral anomalies-V). In the intraoral examination, findings included tooth crowding, enamel hypomineralization in several teeth, a deep and atretic palate, generalized gingivitis, bleeding, gingival hyperplasia, Class III malocclusion, and a right unilateral crossbite.
CONCLUSION
Patients diagnosed with VACTERL syndrome experience significant systemic impairments. The research subject presented compromised oral health, challenges in dental management, delays in neuropsychomotor development, though these are not inherent to the syndrome. It is crucial to prevent oral diseases and provide early dental care for these patients to avoid the need for complex and invasive dental treatments due to systemic impairments.
PubMed: 38693821
DOI: 10.1111/scd.13006 -
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 -
Congenital Anomalies Apr 2024A 27-year-old multiparous woman conceived her fetus naturally. Early second-trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy...
A 27-year-old multiparous woman conceived her fetus naturally. Early second-trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy was artificially terminated at 19 weeks of gestation because of the abnormalities based on the parents' wishes. The parents desired whole-exome sequencing to detect a causative gene using the umbilical cord and the parents' saliva. Compound heterozygous variants (NC_000003.11(NM_052989.3):c.230 T > G/NC_000003.11(NM_052985.4):c.1178A > T) were identified. We described a fetus with a novel compound heterozygous variant in IFT122. The phenotype of this case was severer than of other types of cranioectodermal dysplasia.
PubMed: 38637985
DOI: 10.1111/cga.12569 -
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