Prenatal Torsion of Radial Polydactyly: A Gangrenous Mass at the Base of the Thumb.

A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important.

Giant Cell Tumour of Tendon Sheath of Distal Phalanx of Thumb: A Case Report.

Giant cell tumour of tendon sheath is an uncommon benign soft tissue tumour. Histopathological examination plays a crucial role in the definitive diagnosis of giant cell tumour although pre-operative imaging supports its suspicion. We report a case of a giant cell tumour of the tendon sheath in a 26-year-old man as a painless, firm, localized, slow-growing benign soft tissue tumour of the thumb; managed by complete excision. The patient continues to do well at 7 months post-surgery with no complaints and no signs of recurrence. Giant cell tumour of the phalanges is a locally aggressive entity; therefore delayed or missed diagnosis of giant cell tumour especially of the thumb distal phalanx can be extremely debilitating. Hence, high degree of suspicion and early en bloc resection is the key to its management. Keywords: case reports; giant cell tumors; tendons; thumb.

Effects of Prunus Tomentosa Thumb Total Flavones on adjuvant arthritis in rats and regulation of autophagy.

BACKGROUND: Rheumatoid arthritis (RA) is a slow in taking effect systemic autoimmune disease. Prunus Tomentosa Thumb Total Flavones (PTTTF) has anti-inflammatory and antioxidant properties. OBJECTIVE: The purpose of this study is to the PTTTF on adjuvant arthritis (AA) in rats and to explore the mechanism of autophagy. METHODS: Adjuvant arthritis model was established in rats. The cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor (TNF-α) of rat synovial tissue were determined by RT-PCR. The histopathological varieties of knee joints in AA rats were observed by HE staining. The expressions of autophagy-related proteins ATG5, ATG7, ATG12, Beclin1, Lc3II and Bcl-2 in rat synovial tissue were determined by Western Blotting. RESULTS: PTTTF (50, 100, 200 mg/kg) significantly inhibited inflammation in rats (P< 0.01). PTTTF significantly inhibited inflammatory factor COX in rat synovial tissue. COX-2, IL-1ß, IL-6, IL-17, TNF-α expression (P< 0.05); PTTTF can significantly improve the pathological damage of rat knee joint PTTTF and can significantly inhibited the expression of autophagy-related proteins in rat synovium (P< 0.05 ). CONCLUSION: PTTTF can inhibit adjuvant arthritis in rats and can inhibit the expression of autophagy-related proteins ATG5, ATG7, ATG12, Beclin1, Lc3II and Bcl-2.

Characterization of Trapezial Pommel in Relation to Radiographic and Wear Patterns in Carpometacarpal Osteoarthritis.

BACKGROUND: Trapezial pommel, or ulnar osteophyte positioned at the vertex of the saddle-shaped facet, is a consistent structural appearance in osteoarthritis (OA) of the first carpometacarpal. This study investigates its relation to radiographic measures (modified Eaton staging and thumb OA [ThOA] index) and wear patterns (trapezial surface morphology and cartilaginous eburnation). METHODS: In all, 137 whole trapezia were explanted from 116 patients and evaluated for Eaton staging, morphology (saddle, cirque, or dish), and eburnation (degree of cartilaginous effacement) of the articular surface of the trapezium. In total, 131 Robert's views and 126 stress views were reviewed by 2 blinded senior surgeons for ThOA index and pommel size. Statistical analyses included Spearman correlation and linear regression. RESULTS: Standardized pommel size achieved good intrarater reliability (correlation coefficient: 0.80-0.98) and moderate interrater reliability (correlation coefficient: 0.60-0.67). The ThOA index and pommel size were significantly correlated across Robert's (rs = 0.51) and stress views (rs = 0.64). The ThOA index better distinguished between stages compared with pommel size. All the radiographic measures inversely correlated with preserved cartilage and varied across morphologies. Pommel size differed significantly between dish and saddle, and the ThOA index was significantly different between all morphologies when using stress views. CONCLUSIONS: We reliably quantified the pommel feature and demonstrated significant correlations with other radiographic and topologic measures of arthritic disease. If future studies can demonstrate that the pommel is a pathogenic process in ThOA and its correction can curb disease progression, the identification of the pommel feature may help guide targeted intervention.

A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies.

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.10; rs606231153 NG_009240.2) in the intron 5 of LMBR1. The first affected individual with the disorder was traced back to mid-1700, when some settlers and workers established in Cervera de Buitrago, a small village about 82 km North to Madrid. Clinical and radiological studies of most of the affected members have been performed for 42 years (follow-up of the family by LFGA). Molecular studies have confirmed a pathogenic variant in the ZRS that segregates in this family. To the best of our knowledge, this is the largest family with preaxial polydactyly/triphalangeal thumb reported so far.

[Glomus tumor of subungual presentation in the thumb and use of ultrasound in its diagnosis. Case report and literature review]. / Tumor glómico de presentación subungueal en pulgar y uso de ecografía en su diagnóstico. Reporte de caso y revisión de bibliografía.

INTRODUCTION: the glomus tumor is a benign neoplasm originated in the smooth muscle cells of the vascular glomus. Approximately 80% of lesions are located on the upper extremity and, of these, the majority are in the subungual area. The diagnosis must include imaging tests, among which ultrasound stands out, being a good alternative due to its low cost and accessibility. OBJECTIVE: we present a case of late diagnosis of surgically managed glomus tumor, as well as a review of the existing literature for diagnosis, treatment, and prognosis of this uncommon pathology. CLINICAL CASE: the case of a 52-year-old female patient who reported chronic, burning pain, radiating to the distal phalanx of the thumb with no history of trauma, of 2 years of evolution and which limited her daily life activities, is presented. The exploration with interphalangeal Doppler ultrasound is complemented, being an excellent alternative due to its easy accessibility. A glomus tumor was diagnosed in the interphalangeal thumb. An "H" approach was performed on the interphalangeal fold with subungual dissection with resection of the tumor piece and follow-up by an outpatient clinic where a surgical wound with adequate healing was found. Physical examination with capacity for the mobilization of the distal interphalangeal joint (IFJ) and visual analogue scale (VAS) 1 point. The updated pathological evaluation of the existence of a glomus tumor. CONCLUSIONS: ultrasound is an excellent aid in the diagnosis, as well as in the surgical planning for the treatment of the glomus tumor; for being accessible, low cost and highly effective. The anatomopathological study is the gold standard.

INTRODUCCIÓN: el tumor glómico es una neoplasia benigna originada en las células musculares lisas del glomus vascular. Aproximadamente 80% de las lesiones se localiza en la extremidad superior y, de éstas, la mayoría se sitúa en la zona subungueal. El diagnóstico debe incluir exámenes de imágenes, entre los que destaca la ecografía, siendo una buena alternativa por su bajo costo y accesibilidad. OBJETIVO: presentamos un caso de diagnóstico tardío de tumor glómico manejado quirúrgicamente, así como revisión de la literatura existente para diagnóstico, tratamiento y pronóstico de esta patología poco común. CASO CLÍNICO: paciente femenino de 52 años que refería un dolor crónico, ardoroso, irradiado hacia falange distal del pulgar sin antecedente traumático, de dos años de evolución y que limitaba actividades de su vida diaria. Se complementa exploración con ultrasonido Doppler interfalángico siendo una excelente alternativa por su fácil accesibilidad. Se diagnostica tumor glómico en interfalángica pulgar. Se realiza abordaje en "H" sobre pliegue interfalángico con disección subungueal con resección de pieza tumoral y seguimiento por consulta externa donde se encuentra herida quirúrgica con adecuada cicatrización. Exploración física con capacidad para la movilización de movilización de la articulación interfalángica distal (IFD) y escala visual análoga (EVA) de 1 punto. La evaluación anatomopatológica informó la existencia de tumor glómico. CONCLUSIONES: la ecografía es una excelente ayuda en el diagnóstico, así como en la planificación operatoria para el tratamiento del tumor glómico, por ser accesible, de bajo costo y de alta efectividad. El estudio anatomopatológico es el estándar de oro que da la certeza diagnóstica.

Rasch analysis of the brief Michigan Hand Questionnaire in patients with thumb osteoarthritis.

BACKGROUND: The brief Michigan Hand Questionnaire (brief MHQ) is a 12-item self-reported measure of hand function for patients with hand disorders which has been validated using Classical Test Theory. Rasch analysis can provide more detailed psychometric information. The purpose of this Rasch analysis is to assess the psychometric properties of the brief MHQ for patients with thumb osteoarthritis, and to make recommendations for improvements to the questionnaire if needed.  METHODS: The Michigan Hand Questionnaire and demographic data were collected from 923 thumb osteoarthritis patients treated in specialized clinics for hand surgery and therapy in the Netherlands. Rasch analysis was performed on the 12 items of the brief MHQ using RUMM 2030 to assess the fit of the brief MHQ to the Rasch model. To determine fit, analysis of fit summary statistics, individual person fit and individual item fit were assessed. Threshold distributions were assessed to identify if any items required rescoring. The Person Separation Index was calculated to measure reliability of the questionnaire. Differential item functioning was assessed to identify item bias, and Principal Component Analysis was performed to identify unidimensionality and local dependence. RESULTS: The brief MHQ showed misfit (χ2 = 1312.5, p < 0.0001) with 6 items having disordered thresholds and 9 items requiring rescoring. After deleting 3 of the rescored items due to significant item fit residuals, the brief MHQ had an acceptable reliability (Cronbach's alpha = 0.79). Misfit to the model (χ2 = 49.6, p = 0.0001), multidimensionality (10.2% of t-tests were significant), and item bias from non-uniform differential item functioning for 7 items across many person variables were still found. CONCLUSION: Although no satisfactory solutions were found to correct the misfit to the Rasch model, it is recommended that the response options of the brief MHQ be rescored, and that items 6, 9 and 10 be removed. The lack of unidimensionality indicates that the items do not represent the singular construct of hand disability and that totalling the scores of the brief MHQ does not provide a valid measure of hand disability for people with thumb osteoarthritis. The 37-item Michigan Hand Questionnaire may provide a better assessment of hand disability for patients with thumb osteoarthritis.

Subungual Exostosis of the Hand: A Case Report in a 5-Year-Old Boy and Literature Review.

Subungual exostosis is a relatively uncommon benign tumor that occurs at the distal end of the distal phalanx of the toes and rarely the hands. We present in this article a review of the currently published English literature and provide a case report of a 5 year old male with subungual exostosis of the thumb. A 5 year old male presented with a slow growing mass of the distal dorsal aspect of the left thumb. Radiographs showed dorsal calcifications on the thumb. Surgical removal of the mass and histopathological analysis was performed supporting a diagnosis of subungual exostosis. Post-operatively, the patient had complete excision of the mass, normal nail morphology, no reoccurrence, and no post-surgical complications. Subungual exostosis remains a rare entity especially in the upper extremity. Its cause is not fully understood, nor is there an agreed upon method of treatment. However, with careful dissection during surgical removal good outcomes can be obtained. To our knowledge, this is the largest literature review on subungual exostosis and our case report is an uncommon presentation in the youngest reported male patient. It is our hope that this literature review and case report lend to increased awareness of subungual exostosis and how to diagnose and treat this lesion.

Epithelioid Sarcoma Presenting in the Thumb of a Child.

Epithelioid sarcoma (ES) is a high-grade, soft tissue tumor of mesenchymal origin that rarely occurs in children and is often misdiagnosed as a benign entity. We present the case of a 12-year-old girl with a delayed diagnosis of ES of the left thumb. Radiological examination showed possible calcinosis from inflammation or traumatic injury. However, histopathological and immunohistochemistry studies showed findings consistent with a diagnosis of ES. She was treated with amputation of the interphalangeal joint of the left thumb. This case highlights the clinical and pathologic correlation required for the appropriate diagnosis and treatment of patients with soft tissue masses.

HES1 is a novel downstream modifier of the SHH-GLI3 Axis in the development of preaxial polydactyly.

Sonic Hedgehog/GLI3 signaling is critical in regulating digit number, such that Gli3-deficiency results in polydactyly and Shh-deficiency leads to digit number reductions. SHH/GLI3 signaling regulates cell cycle factors controlling mesenchymal cell proliferation, while simultaneously regulating Grem1 to coordinate BMP-induced chondrogenesis. SHH/GLI3 signaling also coordinates the expression of additional genes, however their importance in digit formation remain unknown. Utilizing genetic and molecular approaches, we identified HES1 as a downstream modifier of the SHH/GLI signaling axis capable of inducing preaxial polydactyly (PPD), required for Gli3-deficient PPD, and capable of overcoming digit number constraints of Shh-deficiency. Our data indicate that HES1, a direct SHH/GLI signaling target, induces mesenchymal cell proliferation via suppression of Cdkn1b, while inhibiting chondrogenic genes and the anterior autopod boundary regulator, Pax9. These findings establish HES1 as a critical downstream effector of SHH/GLI3 signaling in the development of PPD.

Primary Eccrine Porocarcinoma of the Thumb With Metastasis: A Rare Case Report and Literature Review.

ABSTRACT: Eccrine porocarcinoma (EPC) is a rare malignant sweat gland tumor that accounts for approximately 0.005% of all cutaneous carcinomas. It favors the lower extremities. Only 3% of EPCs are on the hand, and only 6 cases occurring specifically on fingers have been previously documented. However, we met a patient with EPC presenting the primary lesion on the left thumb and an extensive cutaneous metastasis on the left forearm. Pathologic findings of axillary lymph nodes confirmed lymphatic metastasis.

Extra-axial chordoma of the thumb: Report of a rare case with clinicopathologic and molecular analysis.

Chordoma is a very rare malignant tumor, with a phenotype that recapitulates notochord, and is chiefly located in the axial skeleton with only few cases reported in the extra-axial skeleton and soft tissues. The diagnosis can be challenging for both clinicians, radiologists and pathologists because of the rarity of tumor, its unspecific radiological pattern and histomorphological similarities to other tumors like extra-skeletal myxoid chondrosarcoma, soft tissue myoepithelioma and metastatic adenocarcinomas, more so on small biopsies. We present a case of a recurrent extra-axial chordoma with a prominent soft tissue component in the left thumb around proximal phalanx of an 80-year-old man, with detailed report of the histopathological, imaging and most importantly molecular features, which are in conformity with the typical profile of notochordal neoplasms. To the best of our knowledge, we report the first DNA-methylation- and the copy number variation analysis of an extra-axial chordoma with a very rare localization, thumb. With this case study we try to give a better understanding of tumor's specification, lessen the diagnostic confusion by highlighting its extra-axial occurrence, and more importantly present substantial molecular data, which might help in providing more therapeutic opportunities in the future.

Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples.

We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targeted gene panels when testing affected offspring born to consanguineous couples. In this way, exomic data from the parents are also made available for carrier screening, to identify heterozygous pathogenetic and likely pathogenetic variants in genes responsible for other recessive conditions, which may pose a risk for subsequent pregnancies.

A Plum On Thumb: A Rare Presentation Of Synovial Sarcoma.

Synovial sarcoma (SS) is a rare and aggressive mesenchymal tumour accounting for around 5-10% soft tissue neoplasms usually found in joints of upper and lower extremities. A 35years old healthy looking male patient from Afghanistan presented with swelling on palmar side of base of thumb from last one year. Seven months back excisional biopsy was taken report of which showed neurofibroma/dermatofibroma with. No evidence of malignancy seen. From last 5months mass reappeared and gradually increased in size with itching sensation and mild pain. On local examination there was 5×4×5 cm reddish mass on palmar surface of base of thumb with extension into mid thenar eminence with diffuse margins. X-ray showed soft tissue density mass with spikes of calcification. Ultrasound showed 4.2×4×4.5 cm heterogeneous solid lesion on anteromedial surface of root of right thumb without any remarkable intralesional calcification and remarkable intralesional vasculature. MRI reported lobulated well defined soft tissue mass eliciting low to intermediate signal on T1 and WIs and bright signal on T2and STIR Vividly enhancing mass. Case was operated mass was excised and biopsy sent. Post op status was unremarkable. Biopsy reported poorly differentiated biphasic synovial sarcoma. No recurrence seen till 3months.

Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K+ channelopathies.

Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K+ channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann-Laband and Temple-Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance, referred to as syndromic neurodevelopmental K+ channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.