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Journal of Feline Medicine and Surgery Dec 2020Polydactyly has been described in two breeds of domestic cats (Maine Coon and Pixie Bob) and in some outbred domestic cats (eg, Hemingway cats). In most cases, feline...
OBJECTIVES
Polydactyly has been described in two breeds of domestic cats (Maine Coon and Pixie Bob) and in some outbred domestic cats (eg, Hemingway cats). In most cases, feline polydactyly is a non-syndromic preaxial polydactyly. Three variants located in a regulatory sequence involved in limb development, named ZRS (zone of polarising activity regulatory sequence), have been identified to be responsible for feline polydactyly. These variants have been found in outbred domestic cats in the UK ( and variants) and in Hemingway cats in the USA ( variant). The aim of this study was to characterise the genetic features of polydactyly in Maine Coon cats.
METHODS
Genotyping assay was used to identify the variant(s) segregating in a cohort of 75 polydactyl and non-polydactyl Maine Coon cats from different breeding lines from Europe, Canada and the USA. The authors performed a segregation analysis to identify the inheritance pattern of polydactyly in this cohort and analysed the population structure.
RESULTS
The allele was identified in a subset of polydactyl cats. Sequencing of two regulatory sequences involved in limb development did not reveal any other variant in polydactyl cats lacking the allele. Additionally, genotype-phenotype and segregation analyses revealed the peculiar inheritance pattern of polydactyly in Maine Coon cats. The population structure analysis demonstrated a genetic distinction between and -free polydactyl cats.
CONCLUSIONS AND RELEVANCE
Polydactyly in Maine Coon cats is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity, and this trait is characterised by genetic heterogeneity in the Maine Coon breed. Maine Coon breeders should be aware of this situation and adapt their breeding practices accordingly.
Topics: Animals; Canada; Cats; Europe; Female; Genetic Heterogeneity; Male; Polydactyly; United States
PubMed: 32067556
DOI: 10.1177/1098612X20905061 -
Genes May 2023Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and...
Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod-cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity. Here, we report nine consanguineous families and a non-consanguineous family with several affected individuals presenting typical clinical features of BBS. In the present study, 10 BBS Pakistani families were subjected to whole exome sequencing (WES), which revealed novel/recurrent gene variants, including a homozygous nonsense mutation (c.94C>T; p.Gln32Ter) in the (NM_006860.5) gene in family A, a homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the (NM_001195306.1) gene in family B, a homozygous nonsense variant (c.720C>A; p.Cys240Ter) in the (NM_015910.7) in family C, a homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the (NM_020347.4) in family D, pathogenic homozygous 1 bp deletion (c.775delA; p.Thr259Leufs*21) in the / (NM_170784.3) gene in family E, a pathogenic homozygous missense variant (c.1339G>A; p.Ala447Thr) in (NM_024649.4) in families F and G, a pathogenic homozygous donor splice site variant (c.951+1G>A; p?) in (NM_024649.4) in family H, a pathogenic bi-allelic nonsense variant in (NM_170784.3) (c.119C>G; p.Ser40*) in family I, and homozygous pathogenic frameshift variants (c.196delA; p.Arg66Glufs*12) in (NM_152384.3) in family J. Our findings extend the mutation and phenotypic spectrum of four different types of ciliopathies causing BBS and also support the importance of these genes in the development of multi-systemic human genetic disorders.
Topics: Humans; Male; Bardet-Biedl Syndrome; Codon, Nonsense; Mutation; Polydactyly; Ciliopathies; Microtubule-Associated Proteins; Cytoskeletal Proteins; Phosphate-Binding Proteins
PubMed: 37239474
DOI: 10.3390/genes14051113 -
Genes Aug 2021Bardet-Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely... (Review)
Review
Bardet-Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet-Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management.
Topics: Bardet-Biedl Syndrome; Fingers; Genetic Association Studies; Genetic Pleiotropy; Humans; Microtubule-Associated Proteins; Mutation; Polydactyly; Protein Interaction Maps; Toes
PubMed: 34573333
DOI: 10.3390/genes12091353 -
Molecular Genetics and Genomics : MGG Sep 2022Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited...
Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of "Nosology and Classification of Genetic skeletal disorders: 2019 Revision". In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand-foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand-foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.
Topics: Brachydactyly; Clubfoot; Humans; Limb Deformities, Congenital; Molecular Biology; Polydactyly; Syndactyly
PubMed: 35907958
DOI: 10.1007/s00438-022-01930-1 -
Journal of Plastic, Reconstructive &... Nov 2021Despite lower extremity polydactyly (LEP) representing the most common congenital foot anomaly with functional and psychosocial implications, the literature is devoid of... (Review)
Review
BACKGROUND
Despite lower extremity polydactyly (LEP) representing the most common congenital foot anomaly with functional and psychosocial implications, the literature is devoid of comprehensive, synthesizing reviews. The purpose of the current review is to identify an evidence-based approach to guide clinical management and shed light on reported functional and esthetic outcomes for postaxial polydactyly.
METHODS
A scoping systematic review of primary clinical studies was performed. Baseline patient characteristics, diagnostic, and surgical approaches were recorded. Main outcomes included immediate postoperative pain, infections, callouses, scar cosmesis, residual deformities, and difficulty with shoe-wear or mobility. A qualitative synthesis of outcomes was performed, and a therapeutic algorithm was developed.
RESULTS
Nine primary studies were identified representing 375 cases of LEP; mean age was 28.8 months (range: 20-40.6 months), and mean follow-up: 42.7 months (range: 1 month-41 years). Ray dominance and the presence of syndactyly were identified as the most important factors for surgical planning; age at surgery was insignificant. A lateral incision approach was used in 78% of cases. Postoperative callouses occurred in 22.1% of cases, infections in 2.5%, and intermittent pain in 11.9%. Significant issues with shoe-wear or mobilization and esthetic residual deformities were reported for 0.78% and 41.2% of cases, respectively. The incidence of residual valgus was 10.6%.
CONCLUSION
LEP is most commonly managed with excision of the non-dominant ray and carries excellent long-term functional outcomes, as presented herein. Numerous techniques are discussed to minimize the risk of esthetic sequalae, although the presence of residual valgus remains a concern. A therapeutic algorithm is proposed for the optimal management of LEP.
Topics: Esthetics; Fingers; Forecasting; Humans; Polydactyly; Toes
PubMed: 33992559
DOI: 10.1016/j.bjps.2021.03.094 -
Joint Diseases and Related Surgery 2022This study aims to compare the usefulness of two systems in classifying thumb duplication cases and give some examples of the cases we believe that are unclassifiable.
OBJECTIVES
This study aims to compare the usefulness of two systems in classifying thumb duplication cases and give some examples of the cases we believe that are unclassifiable.
PATIENTS AND METHODS
Between January 2011 and January 2018, a total of 50 patients (29 males, 21 females; median age: 46.4±68.3 months; range, 1 to 318 months) with thumb duplications as assessed according to the Wassel and Rotterdam classification systems were included.
RESULTS
Duplication was present in the right hand in 28, in the left hand in 21, and in both hands in one patient. According to the Wassel classification system, 45 patients could be allocated in any of the types; however, five patients could not be classified. According to the Rotterdam classification, 47 cases fell into one of the classifications; however, three cases could not be classified.
CONCLUSION
Despite efforts to find the best classification system for thumb duplications, the proposed systems may not fully cover the presented radial polydactyly cases, and additions to the system are required.
Topics: Child; Child, Preschool; Female; Humans; Male; Polydactyly; Thumb
PubMed: 35361090
DOI: 10.52312/jdrs.2022.482 -
American Journal of Medical Genetics.... Sep 2023Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild...
Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild to moderate neurological impairment, and mild endocrinological symptoms. No variant assessed to be pathogenic or likely pathogenic was detected in the GLI3 gene in either child. This syndrome appears to be distinct from the inherited Pallister-Hall syndrome associated with GLI3 variants, which is characterized by hypothalamic hamartoma, mesoaxial polydactyly, and other anomalies. In the individuals described here, manifestations outside of the central nervous system were milder and the mesoaxial polydactyly, which is common in individuals with Pallister-Hall syndrome, was absent. Instead, these children had multiple buccolingual frenula together with the unusual appearance of the fifth digit. It remains unclear whether these two individuals represent a separate nosologic entity or if they represent a milder manifestation of one of the more severe syndromes associated with a hypothalamic hamartoma.
Topics: Child; Humans; Pallister-Hall Syndrome; Hamartoma; Hypothalamic Diseases; Polydactyly
PubMed: 37435845
DOI: 10.1002/ajmg.a.63306 -
Hand (New York, N.Y.) Nov 2022Surgical excision for postaxial polydactyly type B is advocated to avoid long-term complications. Excision with local anesthesia (LA) in infancy represents a safe and...
BACKGROUND
Surgical excision for postaxial polydactyly type B is advocated to avoid long-term complications. Excision with local anesthesia (LA) in infancy represents a safe and effective treatment for this condition, although general anesthesia (GA) is employed by many surgeons. We present a comparison of surgical outcomes, cost, and time between LA and GA to support widespread change in management.
METHODS
A retrospective review of patients under 12 months of age undergoing surgical polydactyly excision by a single surgeon was performed. Anesthesia type, patient demographics, and complications were recorded. Comparisons were made between LA and GA groups on procedure cost, operating time, length of stay (LOS), and time from procedure end to discharge. Stepwise forward regression was used to identify the best model for predicting total costs.
RESULTS
Ninety-one infants with a mean age of 3 months (±1.9) were examined; 51 (56%) underwent LA alone, 40 (44%) underwent GA. Mean operating time was 11.53 ± 4.36 minutes, with no difference observed between anesthesia groups ( = .39). LA infants had a significantly shorter LOS (2.5 vs 3.5 hours; < .05), quicker postoperative discharge (32 vs 65 minutes, < .05), and fewer overall expenses, 2803 vs 6067 U.S. dollars (USD), < .05. Two minor surgical complications (1 in each group) were reported.
CONCLUSIONS
This study demonstrates significantly decreased cost, LOS, and time to discharge using LA alone for surgical excision of postaxial polydactyly type B. Results suggest the approach is quick, economical, and avoids the risks of GA in early infancy.
Topics: Infant; Humans; Anesthesia, Local; Polydactyly; Toes; Anesthesia, General
PubMed: 33631987
DOI: 10.1177/1558944721994255 -
Clinical Dysmorphology Jul 2022Laurin-Sandrow syndrome also known as tetramelic mirror-image polydactyly is a rare congenital disorder characterized classically by polysyndactyly of the hands, mirror... (Review)
Review
INTRODUCTION
Laurin-Sandrow syndrome also known as tetramelic mirror-image polydactyly is a rare congenital disorder characterized classically by polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella) often associated with ulnar and/or fibular duplication. As a pathologic entity, it is heterogeneous, the patients displaying a variety of symptoms. This review aims to analyze the different aspects of the condition, such as clinical findings and methods of treatment to summarize the principal features of Laurin-Sandrow syndrome.
MATERIALS AND METHODS
The review is based on searches on PubMed, Web of Science and Researchgate of the following terms: "Laurin-Sandrow syndrome", "mirror hands", "mirror feet", "tetramelic mirror-image polydactyly", "fibular dimelia" and "ulnar dimelia". Clinical cases, reviews and original articles were included.
RESULTS
As a consequence of our findings, we suggest a modification of the Al-Qattan classification system for Mirror Hand-Multiple Hand Spectrum.
CONCLUSION
Even though it has an extremely low incidence, a thorough understanding of the syndrome enables the surgeon to choose the appropriate treatment with the ultimate goal to improve the patient's life quality.
Topics: Abnormalities, Multiple; Ectromelia; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Nose; Polydactyly
PubMed: 35256564
DOI: 10.1097/MCD.0000000000000420 -
Genes Apr 2023Polydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits....
Polydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits. Postaxial polydactyly (PAP) is the most common form and includes two main types: PAP type A (PAPA) and PAP type B (PAPB). Type A involves a well-established extra digit articulated with the fifth or sixth metacarpal, while type B presents a rudimentary or poorly developed superfluous digit. Pathogenic variants in several genes have been identified in isolated and syndromic forms of polydactyly. The current study presents two Pakistani families with autosomal recessive PAPA with intra- and inter-familial phenotype variability. Whole-exome sequencing and Sanger analysis revealed a novel missense variant in (c.3572C>T: p.Pro1191Leu) in family A and a known nonsense variant in (c.337C>T: p.Arg113*) in family B. In silico studies of mutant KIAA0825 and GLI1 proteins revealed considerable structural and interactional modifications that suggest an abnormal function of the proteins leading to the disease phenotype. The present study broadens the mutational spectrum of and demonstrates the second case of a previously identified variant with variable phenotypes. These findings facilitate genetic counseling in Pakistani families with a polydactyly-related phenotype.
Topics: Humans; Zinc Finger Protein GLI1; Polydactyly; Fingers; Mutation
PubMed: 37107627
DOI: 10.3390/genes14040869