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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 -
European Journal of Medical Genetics Jun 2024CCP110 (centriolar coiled coil protein 110, also known as CP110) is one of the essential proteins localized in the centrosome that plays critical roles in the regulation...
CCP110 (centriolar coiled coil protein 110, also known as CP110) is one of the essential proteins localized in the centrosome that plays critical roles in the regulation of the cell cycle and also in the initiation of ciliogenesis. So far, no human congenital disorders have been identified to be associated with pathogenic variants of CCP110. Mice with biallelic loss-of-function variants of Ccp110 (Ccp110) are known to manifest multiple organ defects, including a small body size, polydactyly, omphalocele, congenital heart defects, cleft palate, short ribs, and a small thoracic cage, a pattern of abnormalities closely resembling that in "ciliopathies" in humans. Herein, we report a 7-month-old male infant who presented with growth failure and skeletal abnormalities, including a narrow thorax and severe brachydactyly. Trio exome analysis of the genomic DNA of the patient and his parents showed that the patient was a compound heterozygote for truncating variants of CCP110, including a frameshift variant NM_001323572.2:c.856_857del, p.(Val286Leufs*5) inherited from the father, and a nonsense variant NM_001323572.2:c.1129C>T, p.(Arg377*) inherited from the mother. The strikingly similar pattern of malformations between Ccp110 mice and the 7-month-old male infant reported herein carrying unequivocal truncating CCP110 variants strongly supports the contention that CCP110 is a novel disease-causative gene.
PubMed: 38857829
DOI: 10.1016/j.ejmg.2024.104955 -
Clinical Genetics Jun 2024Polydactyly is a very common digit anomaly, having extra digits in hands and/or toes. Non-syndromic polydactyly in both autosomal dominant and autosomal recessive forms...
Polydactyly is a very common digit anomaly, having extra digits in hands and/or toes. Non-syndromic polydactyly in both autosomal dominant and autosomal recessive forms are caused by disease-causing variants in several genes, including GLI1, GLI3, ZNF141, FAM92A, IQCE, KIAA0825, MIPOL1, STKLD1, PITX1, and DACH1. Whole exome sequencing (WES) followed by bi-directional Sanger sequencing was performed for the single affected individual (II-1) of the family to reveal the disease causative variant/gene. 3D protein modeling and structural molecular docking was performed to determine the effect of the identified mutation on the overall protein structure. WES revealed a novel biallelic missense variant (c.472G>C; p.Ala158Pro) in exon 6 of the FAM92A gene. The identified variant segregated perfectly with the disease phenotype using Sanger sequencing. Furthermore, Insilco analysis revealed that the variant significantly changes the protein secondary structure, and substantially impact the stability of FAM92A. We report the second FAM92A disease-causing mutation associated with recessive non-syndromic postaxial polydactyly. The data further confirms the contribution of FAM92A in limb development and patterning.
PubMed: 38853702
DOI: 10.1111/cge.14572 -
Prenatal Diagnosis Jun 2024To present the prenatal sonographic features and genomic spectrum of pregnancies with fetal Bardet-Biedl syndrome (BBS).
OBJECTIVE
To present the prenatal sonographic features and genomic spectrum of pregnancies with fetal Bardet-Biedl syndrome (BBS).
METHODS
This was a retrospective study of 11 cases with BBS diagnosed by prenatal ultrasound and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular testing sequencing results, and pregnancy outcomes.
RESULTS
All cases had unremarkable first-trimester ultrasound scans without reporting limb malformations. All had second-trimester abnormal ultrasounds: postaxial polydactyly in nine cases (9/11), renal abnormalities in seven (7/11), reduced amniotic fluid volume in two (2/11), central nervous system anomalies in two (2/11), and ascites in three (3/11). Ten fetuses presented with at least two-system anomalies, and one (Case 11) presented with only postaxial polydactyly. Variants were detected in five genes, including BBS2, ARL6/BBS3, BBS7, CEP290/BBS14 and IFT74/BBS22. Ten pregnancies were terminated in the second trimester, while one continued to term.
CONCLUSION
Enlarged hyperechogenic kidneys and postaxial polydactyly are the two most common sonographic features of fetal BBS. Prenatal diagnosis of BBS can be done with ultrasound and genetic testing although the diagnosis may be made in the second trimester.
PubMed: 38840299
DOI: 10.1002/pd.6619 -
Clinical Dysmorphology Jul 2024
Topics: Humans; Polydactyly; Republic of Korea; Fingers; Toes; Male; Female; Phenotype; Mutation; Asian People
PubMed: 38818822
DOI: 10.1097/MCD.0000000000000489 -
International Health May 2024A birth population-based study was conducted in Danyang, Jiangsu Province, to evaluate major birth defects in emerging regions in China with similar maternal and...
BACKGROUND
A birth population-based study was conducted in Danyang, Jiangsu Province, to evaluate major birth defects in emerging regions in China with similar maternal and neonatal care conditions.
METHODS
We conducted a population-based study in a cohort of infants born in Danyang from 2014 to 2021, including 55 709 perinatal infants. Four categories of isolated birth defects were defined as cases: congenital heart defects (CHDs; n=2138), polydactyly (n=145), cleft lip with or without palate (CL/P; n=76) and accessory auricles (n=93). Infants with congenital malformations were identified by the Chinese Birth Defects Monitoring Network.
RESULTS
Compared with autumn, conception in spring (OR=1.31 [1.16-1.48]) and winter (OR=1.39 [1.23-1.58]) was associated with an increased risk of CHD. Increased risk of CHD, CL/P and accessory auricles was significantly associated with non-local registered residence (OR=1.17 [1.07-1.28], OR=2.73 [1.52-4.88] and OR=2.11 [1.20-3.71], respectively). Individuals of Han nationality were less likely to have polydactyly (OR=0.23 [0.05-0.98]).
CONCLUSIONS
The season of pregnancy was significantly associated with CHDs. Offspring of mothers with non-local registered hometown had greater risks of CHDs, CL/P and accessory auricles.
PubMed: 38801353
DOI: 10.1093/inthealth/ihae034 -
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 -
Advances in Skin & Wound Care Jun 2024In the literature, there is no consensus regarding the surgical management of postaxial polydactyly, and few cases of polymetatarsia with polydactyly have been reported.... (Review)
Review
BACKGROUND
In the literature, there is no consensus regarding the surgical management of postaxial polydactyly, and few cases of polymetatarsia with polydactyly have been reported. Treatment of the complete deformity will prevent further foot and gait disorders.
OBJECTIVE
To identify literature relevant to the operative management of Y-shaped metatarsal with biphalangeal sixth toe and related skin and wound care to improve surgical treatment protocols from a clinical experience perspective.
DATA SOURCES
The authors searched several electronic databases in December 2022 for articles related to postaxial polysyndactyly in the feet and polymetatarsia. Databases searched included PubMed, SciELO, ScienceDirect, Cochrane Database of Systematic Reviews, and Google Scholar gray literature.
STUDY SELECTION
Two independent researchers conducted the searches and read the article titles and abstracts. Studies were included if they were narrative reviews, case studies, or observational studies; written in English or Spanish; and published between 2012 and 2022. Nonhuman studies were excluded. Studies that met the inclusion criteria were fully evaluated. Disagreements between reviewers were resolved by consensus, and when there was no consensus, a senior researcher was consulted.
DATA EXTRACTION
The following data were extracted from the included studies using a standardized form: author and year of publication, study type, number of participants, sex, polydactyly location, polymetatarsia, type of polydactyly, participants' history of hereditary associated diseases or malformations, treatment, removal criteria, and timing of surgery.
DATA SYNTHESIS
Authors evaluated 11 studies of postaxial polydactyly that included a total of 153 participants (64 men, 89 women). They also document their clinical experience with a surgical technique used in cases of bilateral postaxial polydactyly of the foot with a Y-shaped metatarsal with biphalangeal sixth toe.
CONCLUSIONS
Surgical correction with lateral removal of the sixth toe is a resolutive treatment to improve the functionality of the foot, its aesthetic appearance, and the patient's quality of life. Case-specific treatment should be applied and tailored to meet the individual needs. The biomechanics of gait and shoe problems in these patients improve with surgical treatment, without presenting secondary aesthetic problems in skin care.
Topics: Humans; Metatarsal Bones; Polydactyly; Toes; Female; Male; Fingers
PubMed: 38767428
DOI: 10.1097/ASW.0000000000000148 -
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