Congenital three generation wide familial non-syndromic polydactyly.

Polydactyly is typically observed as isolated and sporadic occurrences, although familial cases do exist, albeit with lower frequency, manifesting in various inheritance patterns. In around 30% of polydactyly cases, there exists a familial history, suggesting the probable involvement of a single gene. Given its potential for hereditary transmission, thorough investigation of the patients' parents, first-degree relatives, grandparents, and even great-grandparents for similar disorders becomes imperative. In our clinic, we conducted an analysis focusing on patients presenting with foot polydactyly, along with occurrences of polydactyly among their first- and second-degree relatives spanning two to three generations of family history. The study encompassed three patients and their respective families, including a pair of siblings. We speculate that the inheritance type in our cases was autosomal dominant. Among our patients, one presented with central polydactyly, while the remaining patients and all familial cases displayed postaxial polydactyly. In terms of morphologic classification, one patient had a Y-shaped metatarsal, another had a T-shaped metatarsal, and the third patient exhibited a duplicated ray-shaped anomaly. In our review of the literature, we haven't come across a case spanning three generations like the ones we encountered. Additionally, the presence of a transverse accessory extensor tendon between both extensor tendons in cases with T- and Y-shaped metatarsals intrigued us from an anatomical perspective. Our goal is to present these rare cases of congenital familial polydactyly spanning three generations, highlighting the anatomical variations observed and aiming to contribute to the existing body of literature on the subject.

Persistent Urogenital Sinus Leading to Hydrometrocolpos in a Female Child With Features of McKusick-Kaufman Syndrome.

Persistent urogenital sinus (PUGS) presents as a solitary abnormality or is in association with syndromes, such as congenital adrenal hyperplasia (CAH), VACTERL association (common abbreviation for vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities), Bardet-Beidl syndrome, McKusick-Kaufman syndrome (MKS), and Townes-Brocks syndrome, to name a few. Those affected usually have overlapping phenotypic features of two or more syndromes. Because such children may grow up to be intellectually challenged with multiple other anomalies including gonadal hyperplasia, congenital heart defects, and sensorineural hearing loss, antenatal diagnosis becomes important. Moreover, those who survive into childhood may need a holistic approach to improve their quality of life. This is a rare case of an eight-year-old female child who is a postnatally diagnosed case of congenital heart disease, urogenital sinus with polydactyly, and bilateral hydroureteronephrosis at birth and who is now showing features of multiple overlapping syndromes.

Surgical management of bilateral preaxial and postaxial polydactyly with syndactyly: A case report.

INTRODUCTION AND IMPORTANCE: Polydactyly is the most common congenital malformation in the limbs. However, it is rare for a patient to exhibit concomitant preaxial and postaxial polydactyly alongside syndactyly in both limbs, and there are limited recommendations for such conditions. This report presents a case of bilateral preaxial and postaxial polydactyly with syndactyly of the feet. PRESENTATION OF CASE: A 2-year-old girl was presented with an excess number of toes on both feet and an abnormal connection between the second and third toes. After a physical examination and plain radiography, the patient was diagnosed with bilateral preaxial and postaxial polydactyly with syndactyly. We performed a one-stage surgical correction consisting of ablation at the extra digit of bilateral great and little toes, followed by syndactyly release using z-plasty. The surgery was uneventful, and the parents were satisfied with the result. DISCUSSION: A plain radiograph is necessary for pre-operative planning. We discarded the excess digits for cosmetics and soft and hard tissue for optimal function. It is necessary to preserve the soft tissues, remove the auxiliary digit, realign the digit, and restore the ligaments to preserve digit stability. CONCLUSION: The complexity of this case required a meticulous surgical approach to address the structural abnormalities, restore functionality, and improve cosmetic appearance. In this case, the surgery can be performed in one procedure to minimize patient morbidity.

Trisomy 13 With Bilateral Congenital Anophthalmia: A Case Report.

Trisomy 13, also known as Patau syndrome, is a widely congenital anomaly syndrome characterized by microphthalmia, cleft lip, and palate, microcephaly with a sloping forehead, congenital heart disease, and polydactyly of the limbs. Patau syndrome is identified either prenatally or postnatally. Its survival rate is low, and most of the patients die even before their first year of life. The risk of trisomy 13 is higher in women of advanced maternal age. Brain and cardiovascular abnormalities are typically the primary factors contributing to the syndrome's poor prognosis. We report a case of a male newborn born at full term from a first-degree consanguineous marriage. Upon initial inspection, the patient had classic dysmorphic features, including low-set ears, a cleft lip and palate, a short neck, bilateral anophthalmia, and polydactyly of the limbs. After chromosomal analysis, the diagnosis was made, and a trisomy 13 was discovered.

MYCN in human development and diseases.

Somatic mutations in MYCN have been identified across various tumors, playing pivotal roles in tumorigenesis, tumor progression, and unfavorable prognoses. Despite its established notoriety as an oncogenic driver, there is a growing interest in exploring the involvement of MYCN in human development. While MYCN variants have traditionally been associated with Feingold syndrome type 1, recent discoveries highlight gain-of-function variants, specifically p.(Thr58Met) and p.(Pro60Leu), as the cause for megalencephaly-polydactyly syndrome. The elucidation of cellular and murine analytical data from both loss-of-function (Feingold syndrome model) and gain-of-function models (megalencephaly-polydactyly syndrome model) is significantly contributing to a comprehensive understanding of the physiological role of MYCN in human development and pathogenesis. This review discusses the MYCN's functional implications for human development by reviewing the clinical characteristics of these distinct syndromes, Feingold syndrome, and megalencephaly-polydactyly syndrome, providing valuable insights into the understanding of pathophysiological backgrounds of other syndromes associated with the MYCN pathway and the overall comprehension of MYCN's role in human development.

The Clinical and Mutational Spectrum of Bardet-Biedl Syndrome in Saudi Arabia.

The retinal features of Bardet-Biedl syndrome (BBS) are insufficiently characterized in Arab populations. This retrospective study investigated the retinal features and genotypes of BBS in Saudi patients managed at a single tertiary eye care center. Data analysis of the identified 46 individuals from 31 families included visual acuity (VA), systemic manifestations, multimodal retinal imaging, electroretinography (ERG), family pedigrees, and genotypes. Patients were classified to have cone-rod, rod-cone, or generalized photoreceptor dystrophy based on the pattern of macular involvement on the retinal imaging. Results showed that nyctalopia and subnormal VA were the most common symptoms with 76% having VA ≤ 20/200 at the last visit (age: 5-35). Systemic features included obesity 91%, polydactyly 56.5%, and severe cognitive impairment 33%. The predominant retinal phenotype was cone-rod dystrophy 75%, 10% had rod-cone dystrophy and 15% had generalized photoreceptor dystrophy. ERGs were undetectable in 95% of patients. Among the 31 probands, 61% had biallelic variants in BBSome complex genes, 32% in chaperonin complex genes, and 6% had biallelic variants in ARL6; including six previously unreported variants. Interfamilial and intrafamilial variabilities were noted, without a clear genotype-phenotype correlation. Most BBS patients had advanced retinopathy and were legally blind by early adulthood, indicating a narrow therapeutic window for rescue strategies.

Treatment for Lateral Ray Polydactyly with Brachydactyly of the Foot.

Surgical methods for lateral ray polydactyly with brachydactyly of the foot include simple toe ablation and toe lengthening. However, there are few reports on comparative studies, and there is no standard treatment. We retrospectively investigated cases of lateral ray polydactyly with brachydactyly treated at our department and related facilities. In our study, the prevalence of Hirai-Togashi classification type IV was 8.8% (13/147 toes). Five patients did not request toe lengthening and underwent simple ablation, resulting in a shortened remaining toe in these 5 patients. The surgical methods for toe lengthening were pedicle bone grafting in 2 cases and on-top formation in 6 cases. Good results can be obtained in the most common phalangeal type cases, but care must be taken in cases with block-shaped metatarsal heads to avoid poor toe alignment.

Ectrodactyly with Polydactyly in a Dog-Case Description and Description of Surgical Therapy with Resection and Fusion Podoplasty.

OBJECTIVE: To describe a rare congenital deformity of the phalanges and the surgical details and outcome in a dog with ectrodactyly combined with polydactyly. STUDY DESIGN: Single case report. ANIMAL: A 3.5-month-old male intact mixed breed dog with forelimb lameness and paw malformations. METHODS: Surgery was performed on a dog with a congenital limb deformity consisting of resection of the extra bone and soft tissue structure to prevent further subluxation of the remaining metacarpals. Stabilisation consisted of a cortical screw in compression and a K wire across the proximal metacarpals. RESULTS: Postoperative radiographs showed adequate implant positioning and good reduction of the proximal metacarpal row. At six weeks, the dog showed improvement in limb function and weight bearing. Major complications occurred at twelve weeks, and revision surgery with implant removal was required. At six months, the dog showed near normal range of motion and no lameness. CONCLUSIONS AND CLINICAL RELEVANCE: The decision to perform surgery on a dog with limb deformity resulted in an almost physiological gait, and the dog showed no abnormalities in daily life. This report adds to the literature on congenital limb deformities by describing the combination of ectrodactyly and polydactylism in a canine species, including the surgical approach and outcome. However, the optimal management of this heterogeneous condition is currently unclear.

A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.

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.

Mirror Foot: Surgical Approach for Esthetic and Functional Improvement.

Mirror foot is a rare congenital anomaly on to the spectrum of complex foot polydactyly. It may occur in isolation or associated with other malformations or genetic syndromes. This is a subject little described in the literature, with few publications on its treatment. We herein report the case of a 4-year-old female patient who presented with a left foot with 8 fingers, without other associated deformities, whose complaints included the impossibility of wearing shoes and social stigma. Radiographically, eight metatarsi with their respective phalanges, five cuneiform bones, and absence of bone deformities in the hindfoot were verified. The surgical approach was chosen in order to promote functional and esthetic improvement, as well as a better adaptation to the use of closed shoes, according to the patient's and family's desire. A dorsal and plantar V incision was performed, with resection of three supranumerary rays, including three central metatarsi with their nine corresponding phalanges, two cuneiform bones, tendons and extra digital nerves, followed by suture of the intermetatarsal ligaments, preserving the fingers with normal appearance, decreasing the width of the foot, and maintaining proper support. The reduction was maintained through transmetatarsal fixation with Kirschner wires. The postoperative period went on with the use of a walking boot and zero load, without complications, with removal o the Kirschner wires and allowing load on the limb after twelve weeks.

A Rare Case of Unilateral Fetal Cataract and Coincidental Polydactyly in Congenital Toxoplasmosis.

Congenital toxoplasmosis is caused by transplacental infection of Toxoplasma gondii during pregnancy. We present a case of a congenital toxoplasma with intracranial calcifications, microcephaly, growth restriction, a unilateral cataract that developed in the third trimester, and a coincidental post-axial-polydactyly. Antenatal imaging findings are important to guide further testing and confirmation of diagnosis, it is important to know all possible associations and prognoses for timely counseling, testing, and intervention. To our knowledge, no case has been published with findings of unilateral cataract in congenital toxoplasmosis and associated coincidental polydactyly. Therefore, we wish to add this case to the current scientific literature.

Polydactyly-Myopia Syndrome: Genetic and Ophthalmologic Perspectives.

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.

A Genotyped Case of Townes-Brocks Syndrome with Absent Pulmonary Valve Syndrome from Turkey.

Townes-Brocks syndrome (TBS) is a rare syndrome characterized by triad of anal, ear, and thumb anomalies. Further malformations/anomalies include congenital heart diseases, foot malformations, sensorineural and/or conductive hearing impairment, genitourinary malformations, and anomalies of eye and nervous system. Definitive diagnosis for TBS is confirmed by molecular analysis for mutations in the SALL1 gene. Only one known case of TBS with absent pulmonary valve syndrome (APVS) has been previously described to our knowledge. Here, we report a newborn diagnosed with TBS with APVS and tetralogy of Fallot (TOF) who was found to carry the most common pathogenic SALL1 gene mutation c.826C > T (p.R276X), with its surgical repair and postoperative follow-up. To our knowledge, this is the first genotyped case of TBS from Turkey to date. TBS should be suspected in the presence of ear, anal, and thumb malformations in a neonate. If a patient with TBS and TOF-APVS needs preoperative ventilation within the first months of life, this implies prolonged postoperative intubation and increased risk of mortality.

A de novo Mutation (p.Gln277X) of Cyclin D2 is Responsible for a Child with Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome.

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 de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 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 CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

Bardet-Biedl syndrome with unique manifestations of congenital giant nevi and refractory anemia: a case report from Palestine.

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.

Postaxial polydactyly of the bilateral hand in toddler: Case report and literature review.

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.

A novel variant in IFT122 associated with a severe phenotype of cranioectodermal dysplasia.

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.

A novel GLI3 frameshift mutation in a Chinese pedigree with polydactyly: A case report.

Background: GLI3 gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister-Hall syndrome (PHS, MIM: #146510), and isolated polydactyly (IPD, MIM: #174200, #174700). Reports on IPD-associated GLI3 mutations are rare. In this study, a novel GLI3 mutation was identified in a Chinese family with IPD. Results: We report a family with six members affected by IPD. The family members demonstrated several special phenotypes, including sex differences, abnormal finger joint development, and different polydactyly types. We identified a novel frameshift variant in the GLI3 gene (NM_000168.6: c.1820_1821del, NP_000159.3: p.Tyr607Cysfs*9) by whole-exome sequencing. Further analysis suggested that this mutation was the cause of polydactyly in this family. Conclusions: The discovery of this novel frameshift variant in our study further solidifies the relationship between IPD and GLI3 and expands the previously established spectrum of GLI3 mutations and associated phenotypes.

Risk of congenital anomalies in children who have a sibling with cancer: A matched cohort study.

PURPOSE: We assessed the risk of congenital anomalies in children who have a sibling with cancer. METHODS: We performed a matched cohort study of children born between 2006 and 2022 in Quebec. The exposure was having a sibling with cancer. Exposed children were matched to unexposed children based on sex, number of siblings, birth order, and year. The outcome included heart defects, orofacial clefts, and other anomalies. Using conditional logistic regression, we estimated odds ratios (OR) and 95 % confidence intervals (CI) for the association between having a sibling with cancer and the likelihood of having a congenital anomaly. RESULTS: A total of 2403 children who had a sibling with cancer were matched to 240,257 unexposed children. Congenital anomalies were more frequent in children who had a sibling with cancer compared with unexposed children (10.3 % vs 8.9 %). Overall, having a sibling with cancer was only weakly associated with congenital anomalies (OR 1.18, 95 % CI 1.04-1.35). Exposed children tended to have greater odds of polydactyly/syndactyly (OR 1.89, 95 % CI 1.11-3.21) and urinary defects (OR 1.50, 95 % CI 1.09-2.08) compared with unexposed children. CONCLUSIONS: Children who have a sibling with cancer have an only weakly elevated risk of congenital anomalies.

Whole-Genome Sequencing for Identifying Candidate Genes Related to the Special Phenotypes of the Taihu Dianzi Pigeon.

The Taihu Dianzi pigeon is a breed native to China, and its special piebalding, crest, and polydactyly phenotypes are the result of artificial and natural selection. Here, we analyzed the genetic differences among three kinds of pigeons with different phenotypes at the genomic level. A selective sweep was conducted based on the fixation index (FST) and nucleotide diversity (π) ratio, and the results revealed that MC1R was related to the formation of the distinctive piebalding of the Taihu Dianzi pigeon. Combined with the results of genome-wide association studies, we identified candidate genes associated with the crest (SMYD and STOX2) and polydactyly (SLC52A3 and ANGPT4). The candidate genes identified in this study and their variants may be useful for understanding the genetic mechanism underlying the special phenotypes of the Taihu Dianzi pigeon. This study provides new insights into the genetic factors that may influence the formation of the special piebalding, crest, and polydactyly characteristics in pigeons.